Research

The Chinese Medical Doctor Association (CMDA) is a national, voluntary, nonprofit, professional association of the more than two million practicing physicians in China. Representing the collective view of Chinese medical professionals, CMDA is committed to advocating for better health and supporting research programs that can improve the safety, quality and effectiveness of healthcare in China. The following listed are ongoing research programs that CMDA sponsors:

• China Cardiometabolic Registries (CCMR)

CCMR is one of the largest registry/cohort study programs ever being conducted in China. It is designed to better understand the epidemiology and unmet medical needs in major cardiovascular and metabolic diseases, better establish evidence of clinical outcomes, better define gaps in medical guidelines, better enhance the values of innovative medical therapy and diagnostics, and ultimately better improve the quality of patient care. CCMR is supported by Ministry of Health (MOH), collaborated with China Medical Doctors Association (CMDA) through Chinese College of Cardiology Physicians (CCCP), Chinese Endocrinologists Associations (CEA), and organized by VitalStrategic Research Institute (VSRI). It is governed by an advisory board that is comprised of internationally renowned opinion leaders from Europe, US, and China.

• Coalition for Clinical Research in Cardiovascular and Metabolic Diseases (CCRC)

The Chinese Medical Doctor Association (CMDA) and Shanghai Vitalstrategic Research Institute (VSRI) has announced in April 2010, to establish the “Coalition for Clinical Research in Cardiovascular and Metabolic Diseases”.
The aim of the coalition is to improve cardiovascular and metabolic disease clinical research in China and to increase the influence of Chinese clinical research internationally. The research results will benefit patients as well as medical professionals. The main tasks of CCRC include,

• Enhancing the influence of “China cardiovascular and metabolic diseases registry (CCMR)" nationally and internationally
• Accelerating the implementation and execution of CCMR tasks
• Facilitating the corporations between CMDA and healthcare industry
• Providing guidance and trainings for better conduct Phase II-IV clinical studies, real-time effectiveness research, epidemiological research, and comparative effectiveness research.

3.? China Chronic Diseases Registry
The Chinese Medical Doctor Association (CMDA) and Shanghai Vitalstrategic Research Institute (VSRI) has announced in August 2011 to establish the “China Chronic Diseases Registry” program.

The aim of China Chronic Diseases Registry (the “Registry”) program is to better ?understand and assess the current inpatient and outpatient diagnosis and treatment patterns for chronic disease management. It is developed to enabling more systemically, accurately and timely reflects unmet clinical needs, healthcare trend and challenges, and defines ways to improve the quality of health care. Each registry study will have specific research objectives, research protocols, research sites, and will utilize existing hospital electronic records systems to enhance the research efficnecy. Data collection and analysis will be according to GCP standards.

Results of these registry studies, not only can help pharmaceutical and medical device industry to better understand the actual real-world medical needs, thus develop better R & D and marketing strategies, but also help the hospital management to better assess the implementation of treatment pathways, quality of care, priorities of medical staff training, and other ways to improve health care efficiency and patient satisfaction. To align with the Ministry of Health’s call for better chronic disease management strategy, our registry program will first focus on cardiovascular disease, diabetes, cancer, and respiratory diseases.

Registry studies are very common in Europe and North America. For example, the American College of Cardiology has conducted the large-scale “National Cardiovascular Data Registry” in the U.S since 1999. It has been reported quite often that registry studies has helped implement and assess medical guidelines and improved management of chronic disease. Before the EMR system becomes more mutual and reliable, the prospective registry study will help fill the gaps for better collect and analyzing real world practice information during the next few years.

• Contact Information

For interest in collaborating with CMDA on any of the ongoing research program, please contact us:
info@cmda.org
info@vitalstrategic.com

Clinical Pathways as a Strategy for Improving Care: Problems and Potential

Abstract
In an era of increasing competition in medical care, critical pathway guidelines have emerged as one of the most popular new initiatives intended to reduce costs while maintaining or even improving the quality of care. To prevent wasteful spending on the use of medical care while elevating the standard of patient care at the same time, hospitals and organizations will usually utilize models such as: total quality management, case management, patient-centered care units, outcomes management, clinical path and so on to promote the same goal. Developed primarily for high-volume hospital diagnoses, critical pathways display goals for patients and provide the corresponding ideal sequence and timing of staff actions for achieving those goals with optimal efficiency.
America has established the SITO (The Services interaction targets for opportunities) foundation in 1971. In 1981, the country utilized the DRG (Diagnosis related group) as a mean of payment to better control spending in the healthcare units, lowering the hospitalization duration of the average patient.
Despite the rapid dissemination of critical pathway programs in hospitals throughout the United States, many uncertainties remain about their development, implementation, and evaluation.In addition, serious concerns have been raised about their effect on patient outcomes and satisfaction with care, physician autonomy, malpractice risks, and the teaching and research missions of many hospitals. Underlying these concerns is the absence of data from controlled trials to evaluate the effects of critical pathways.
Physicians should understand the potential benefits and problems associated with critical pathways because physicians are increasingly being asked to provide leadership for pathway programs.Physicians and other health service investigators should also develop methods to study pathways in evolving health care settings. Although the promise of reduced costs and improved quality is enticing, the gaps in our knowledge about critical pathways are extensive; therefore, like any new health care technology, pathway programs should be fully evaluated in order to understand the conditions under which that promise may be fulfilled.
In recent years, intense pressures to reduce the costs of health care have led many health care organizations to seek strategies that reduce resource utilization while maintaining the quality of care [1-5]. Among the most popular of the methods intended to meet this challenge are critical pathways. Critical pathways are management plans that display goals for patients and provide the corresponding ideal sequence and timing of staff actions to achieve those goals with optimal efficiency [6-8]. Interest in critical pathways has increased tremendously during the past several years as early anecdotal reports of their cost-saving potential have been disseminated, usually outside the peer-reviewed medical literature [7, 9, 10].
The rapid push for critical pathway implementation comes from intense competitive pressures and the persistent evidence of unexplained variation in medical practice [11, 12]. Many managed care organizations have added their weight to this process by mandating certain critical pathways or seeking partner hospitals that are willing to develop their own [7]. However, no controlled study has shown a critical pathway to reduce the duration of hospital stay or to decrease resource use, nor has any study shown critical pathways to improve patient satisfaction or outcomes [13]. Nevertheless, like other promising medical technologies, critical pathways are being disseminated before controlled trials have been done to evaluate their effectiveness.
Despite the lack of data, an increasing number of physicians will be asked to participate in critical pathway development. Even more will find that their hospitalized patients are already “on” pathways that they may or may not have endorsed. To enhance the effectiveness of critical pathways—and minimize the disruption to the patient–physician relationship—physicians and other caregivers must understand the origin, potential benefits, and potential pitfalls of this new method.
Critical Pathways: A New Form of Clinical Guideline
Critical pathways have varying formats and are known by many names, including critical paths, clinical pathways, and care paths. Interpreted formally, a critical pathway is the sequence of events in a process that takes the greatest length of time. Like the techniques of continuous quality improvement, critical pathway techniques were first developed for use in industry as a tool to identify and manage the rate-limiting steps in production processes [14-17]. First developed in the 1950s, the Critical Path Method was frequently linked with a similar approach, the Program Evaluation and Review Technique, to coordinate multiple contractors or persons in a project by identifying the key sequence of events, or “critical path,” the requirements of which would drive the timeline of the overall project [18, 19]. Critical pathway techniques have subsequently been applied to projects as diverse as construction, civil engineering, town planning, marketing, ship building, product design, and equipment installation [6].

Critical pathways were first developed and applied to health care in the 1980s, when prospective payment systems focused greater interest on potential methods to improve hospital efficiency [6]. Most of the first critical pathways in hospitals were developed by nurses for nursing care alone [20, 21], but multidisciplinary teams soon began developing pathways to encompass all aspects of care for hospitalized patients [22-24].
In general, efforts to develop critical pathways in health care have not incorporated the formal techniques used by industrial predecessors to identify the true “critical” pathway in any care process [18, 25]. Instead, when critical pathways are used to plan medical care, the specific goals usually include the following:
1. Selecting a “best practice” when practice styles vary unnecessarily.
2. Defining standards for the expected duration of hospital stay and for the use of tests and treatments.
3. Examining the interrelations among the different steps in the care process to find ways to coordinate or decrease the time spent in the rate-limiting steps.
4. Giving all hospital staff a common “game plan” from which to view and understand their various roles in the overall care process.
5. Providing a framework for collecting data on the care process so that providers can learn how often and why patients do not follow an expected course during their hospitalization.
6. Decreasing nursing and physician documentation burdens.
7. Improving patient satisfaction with care by educating patients and their families about the plan of care and involving them more fully in its implementation.
The general format of critical pathway guidelines is the Gantt chart, which outlines the suggested patient care process based on a time-task matrix, listing the components of care in one column and cross-aligning these entries with columns pertaining to time [8]. Figure 1 is an example of such a chart for a critical pathway for patients who have had coronary artery bypass graft surgery. Categories of multidisciplinary staff actions are listed in the first column of the pathway, with specific actions for each day of hospitalization. As indicated in Figure 1, a patient's diet is expected to progress successfully from ice chips to clear liquids on the first day after surgery. For all other categories of patient care, critical pathways likewise explicitly mark the transition points of patient progress and lay out a coordinated “map” of staff activities to achieve those transitions in the most efficient way possible.

Figure 1. This general time-task matrix format, also known as a Gantt chart, indicates for each day of care the corresponding multidisciplinary staff actions and expected patient outcomes. CT equals chest tube; CXR equals chest radiograph; EKG equals electrocardiogram; ET equals endotracheal tube; ICU equals intensive care unit; MD equals physician; PO equals by mouth; POD1 equals first postoperative day; . The first 2 days of a simplified critical pathway for patients who have had cardiac surgery.
Critical pathways differ from most clinical guidelines, protocols, and algorithms in several key respects. First, clinical guidelines often address the appropriateness of care by delineating the indications for tests or treatments. Critical pathways, on the other hand, have almost always focused on the quality and efficiency of care after decisions have already been made to admit the patient or perform the procedure. Another way in which critical pathways differ from most clinical guidelines is that they are multidisciplinary in their development and in the scope of their implementation. Critical pathways are also designed along specific timelines, sometimes even in hour-by-hour detail, for indicated actions, and pathways not only spell out these specific actions but also enumerate expected intermediate patient outcomes that serve as checkpoints for the performance of both the patient and the pathway.
Yet another distinguishing feature of critical pathways is that their comprehensive design allows them to be used as a part of the patient record, often replacing other documentation entirely [6, 24]. All staff interventions and intermediate clinical outcomes that occur as expected can be simply initialed on the critical pathway document. If staff actions or intermediate patient outcomes do not occur as expected, however, a “variance” from the pathway is said to have occurred [26]. Variances, too, can be noted on the document, along with an explanation of their cause or causes, and, if needed, a plan can be described to return the patient to the expected course of treatment and outcomes.
Critical Pathway Development
Topic Selection
Critical pathways are typically developed for the hospital care associated with high-volume, high-cost diagnoses and procedures, particularly those for which inefficient variation in the process of care is thought to exist [6]. Surgical procedures, such as coronary artery bypass graft surgery and total hip replacement, lend themselves particularly well to critical pathways because the care process differs relatively little from patient to patient. For this same reason, obstetric procedures such as normal vaginal delivery and cesarean section have also been subjects of pathways in many institutions [24].
For most medical diagnoses, however, patient care has proved more difficult to translate successfully into critical pathways because of the greater heterogeneity among patients and problems [6, 27]. Some institutions have reported that pathways fail when used for medical patients who have either multiple problems and therefore multiple relevant pathways or a problem that does not fit neatly within any single standardized pathway [27-29]. Despite these concerns, however, pathways have been designed and implemented at many institutions for medical diagnoses such as myocardial infarction, stroke, and deep venous thrombosis [23].
Team Composition
The group that is organized to develop a critical pathway should be multidisciplinary in order to bring to the table the knowledge and perspectives that are necessary to view the care process in its entirety. Although many institutions have appointed nurses as the leaders of critical pathway teams [6], we have found that having a physician-expert lead each team lends credibility to the pathways and builds a foundation of support among all clinicians. Each pathway team should also have a group facilitator from the hospital administration, a housestaff physician, a member of the quality management department who has expertise in critical pathway methods, and a community-based primary care physician, whose perspective on inpatient care is likely to differ from that of hospital-based physicians.
The lack of active involvement by physician-experts is cited as a key reason for the failure of pathway programs; critical pathways that are developed without physician input have ended up sequestered in a part of the medical record where physicians do not often look [27, 30]. Simply gathering physicians, nurses, and other staff around the same table, however, may not be enough to generate the level of teamwork and communication necessary for success. It is an important challenge, especially for physicians trained in an individualistic ethic, to learn how to participate in and lead these teams effectively [31, 32].
The Pathway Development Process
The key steps in developing critical pathways vary from institution to institution and from diagnosis to diagnosis. Nevertheless, two steps common to all pathway development processes have been described [6, 8, 29].
Step 1. Evaluate the current process of care. The manner and extent to which critical pathway programs evaluate the current care process vary widely [6, 9, 18, 25]. All authors urge that chart review be done to identify current variations in care and to understand the complex and interdependent actions of all staff. Another goal of evaluating the current care process is to identify specific outcome criteria for discharge and for reaching intermediate patient goals so that these criteria can be made key elements of the pathway. However, to truly delineate the time-limiting path and key precedent relations among various activities, some authors have also stressed moving beyond simple chart review and brainstorming to the use of formal critical pathway techniques, including Critical Path Method and Program Evaluation and Review Technique, activity and precedent tables, flowcharts, and slack time determinations [18, 25]. Although a full description of these methods in pathway development is beyond the scope of this article, good descriptions can now be found in the medical literature [18, 25, 33].
At our institution, we have found that critical pathway teams benefit from a breakdown of the costs of hospitalization. Team members are often surprised to learn the relative importance of certain costs, such as pharmacy costs, in the overall cost of care for their patients. Knowing the relative significance of different types of costs has helped our teams ask new questions about the care process, and the answers have helped them develop critical pathways with targeted innovations and changes to improve efficiency.
Step 2. Evaluate medical evidence and external practices. In evaluating the current care process, critical pathway teams discover variations and may find that the medical literature can help inform clinical debates about the effectiveness and appropriateness of tests and treatments. We have let members of each critical pathway team decide, in the course of their discussions, when and how to evaluate the literature.
However, for many teams, the medical literature has been of limited importance in pathway development. Many of the questions of immediate importance to a pathway team, questions relating to the most effective execution of care, have rarely been topics of well-controlled studies. For example, solid evidence on the effect of different durations of hospital stay on clinical outcomes or patient satisfaction is uncommon [34].
Given the dearth of evidence in the medical literature, anecdotal evidence, or “benchmarking,” can be helpful to critical pathway teams [6]. Many of our critical pathway teams have benefited from discussions on the care process with colleagues at other institutions or from examinations of critical pathways already in use at other sites. We know of no collaborative efforts to develop critical pathways at the regional or national level, but such efforts might offer the opportunity to build a broader-based consensus on controversial issues such as suggested durations of hospital stay for various conditions. However, although it would be less costly to adopt critical pathways directly from consensus groups or other institutions, we share the impression of others that the active participation of local physicians, nurses, and other staff in designing their own pathway is essential to the success of these programs [29, 35].
Critical Pathway Formats
Although the basic format of critical pathways is that of the task-time matrix, the document itself can be formatted in several different ways [8, 25]. Some pathways are constructed as continuous, multipaged foldouts with space left for pathway documentation alongside standard progress notes. Other pathways are formatted as single-paged educational tools, without space for direct documentation [23, 26]. Some institutions are now experimenting with the computerization of pathways, linking them to laboratory test and pharmacy ordering systems, with the goal of eliminating the paper chart entirely [28, 36].
Having critical pathways serve as nursing documentation tools often competes with the goal of involving physicians in these programs, as is shown by the variety of formats [27, 37]. Some critical pathways try to account for nearly every action that would occur in the care process so that nurses can simply check off boxes when these actions take place. However, the level of detail such documentation necessitates makes daily critical pathways difficult for physicians to review, because they may list hundreds of specific tasks and patient outcomes.
Creating a format that will be used as part of the permanent medical record and that will be accepted and used by physicians has been noted as the chief hurdle faced by critical pathway programs [27, 29]. One author has suggested that the time-task matrix common to most critical pathway formats is too foreign to physicians and that pathways formatted as standardized order sets may have the best chance at winning physician acceptance [27].
At our institution, we use a format that not only lists all patient actions for nursing documentation purposes but also identifies certain “key” elements in bold print that have been selected by the critical pathway team as most relevant to the physician. An example of this format is shown in Figure 2, a simplified version of a page from our cardiac surgery pathway. In this format, both nurses and physicians document on the same sheet. Physicians are encouraged to view the critical pathway as a whole, but if they prefer, they can focus rapidly on the key highlighted steps in the patient care process. The critical pathway document is kept in the “physician” section of the medical record, and physicians continue to write their own notes in sections of the critical pathway set aside for that purpose, while nurses document the achievement of all actions or expected outcomes by signing their initials in the appropriate box for their shift (“D” for day, “E” for evening, and “N” for night). If actions or outcomes do not occur as expected, nurses sign instead in the variance (“VAR”) box, and in their written notes indicate an action plan for the variance.
Figure 2. A simplified version of a page from a critical pathway for patients who have had coronary artery bypass surgery. This page shows some of the actions and intermediate outcomes that are expected to occur on the day of surgery. A level of detail suitable for nursing documentation is included, but, to encourage physicians to participate, only the two elements that are the most important to them are indicated in bold print: 1) ordering an anesthesia consult as part of an early extubation protocol and 2) adequate pain control with analgesics. D equals day nursing shift; E equals evening nursing shift; N equals night nursing shift; VAR equals variance. Documentation of expected actions and outcomes.
Although our strategies for balancing documentation needs and physician involvement continue to evolve, our experience with this format has been favorable. We have no formal measure of staff acceptance, but it is our subjective impression that this format has allowed our physicians and nurses to work comfortably together within the same critical pathway document.
Documenting and Analyzing Variances
Another difficult challenge in pathway development is designing an effective method for documenting and analyzing variance data [28]. Variances are patient outcomes or staff actions that do not meet the expectations of the critical pathway. Variances in staff actions are usually considered omissions from what was suggested in the pathway, but they can also be “extra” actions that may represent overutilization. Nevertheless, perhaps because first-generation critical pathways usually focus on accelerating the pace of staff actions, most systems of variance analysis have evaluated only actions or outcomes that are expected but do not occur on time [26-28].
Variance data provide the essential tool that places critical pathways squarely within the tradition of continuous quality improvement. However, because every step in a critical pathway can be considered a source of variance if not completed or achieved within the time frame proposed by the pathway, many hospitals have found their data collection efforts overwhelmed with variances, most of which are not even important for evaluating clinical outcomes, patient satisfaction, or resource use [27-29].
To overcome this difficulty, institutions have developed many different strategies to identify and measure variances, and these strategies continue to evolve [28, 38-41]. Computer versions of critical pathways offer the advantage of being able to gather and analyze variance data without human intervention, although the interpretation of large amounts of such data remains time-intensive [36]. At our institution, we are testing an approach in which variances are defined and measured only at key transition points, or “gateways,” within each pathway [18]. Each critical pathway team uses a combination of intuitive and quantitative methods to select several key points at which a patient outcome that does not occur as expected indicates a significant risk for not meeting future time goals and ultimately for not meeting the goal for duration of hospitalization. Failure to “pass through” a gateway at the expected time serves as a signal that a significant variance from the expected course has occurred, and the reason for that variance and a plan to address it is then documented by the patient's nurse.
An example of this gateway variance method is shown in Figure 3. The gateway identified here is the anticipated transfer of a patient who has had cardiac surgery from an intensive care unit to an intermediate care ward within 24 hours after surgery. If the patient reaches and passes through this gateway at the expected time, no variance data are generated, even if other specific actions of the pathway are not completed. However, if the patient is not transferred from the intensive care unit within the expected time and needs to stay in the intensive care unit for an additional day, then a gateway variance is recorded in a large box at the top of the critical pathway page for that day. Whenever a gateway variance is recorded, the nurse also notes the reason or reasons the patient did not “pass through” the gateway on time. These data on gateway variance “causes,” although subjective, can help one evaluate current hypotheses and even gain new insights into the care process. By focusing on the frequency of gateway failures and their underlying causes, the goal of our variance system is to provide clinicians with insights into critical steps in the care process without inundating them with less relevant process data.
Figure 3. This figure shows a simplified version of the page of a critical pathway for patients who had had coronary artery bypass surgery that is used if a patient does not achieve the “gateway” of expected transfer from the intensive care unit to an intermediate care bed within 24 hours after surgery. Reasons for the variance are documented by the nurse who is caring for the patient at the beginning of the patient's second day in the intensive care unit, and these data are used in ongoing evaluations of the pathway and the care process. D equals day nursing shift; E equals evening nursing shift; ECG equals electrocardiogram; N equals night nursing shift; VAR equals variance. Variance documentation.
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Critical Pathway Implementation
The early experience in the implementation of critical pathways has been mixed. Enthusiastic qualitative reports have described benefits for patient empowerment and physician-nurse interactions [9]. Many case studies and uncontrolled comparisons have also cited reductions in duration of hospital stays of 5% to 40%; cost reductions of as much as 33%; significant improvements in readmission rates, wound infections, and other clinical outcomes; and significant increases in the rate of compliance with generally accepted standards of care [10, 21-23, 42].
However, other reports have not been as favorable. A well-controlled study of a critical pathway for patients with stroke showed no significant effect on costs or clinical outcomes [13]. Also, according to some recent anecdotal reports, many critical pathway programs have met with physician resistance, and, in several cases, hundreds of pathways created by flourishing programs fell quickly into disuse and even disregard, despite their early success [27-29].
From both the successes and the failures, several themes emerge regarding pathway implementation. Strong support from hospital leaders is important to communicate the commitment of the institution to the pathways. Piloting each critical pathway in a subset of patients helps identify areas in which the pathway may need to be changed and builds trust among hospital staff [27].
Before pathway programs are implemented, education of all hospital staff who will be involved is vital [29]. Nurses, physicians, and other care providers who have not been directly involved in the development of the pathway should understand and accept the goals of the pathway and the justification for the suggested duration of the hospital stay and care process as a whole. This educational effort should include discussion of the methods for collection and analysis of data on variance from the critical pathway. Clinicians may be concerned that they will be punished in some way if they do not manage their patients such that they meet all patient outcome and action goals proposed by the pathway. Because fear tends to accompany any significant change, these concerns should be discussed openly.
A central part of pathway implementation is the definition of roles and responsibilities on a day-to-day basis. Will physicians document on the pathway? Will nurses and physicians indicate variances from the pathway, and who will have the responsibility for creating the plans to address the variances? Should a case manager manage variance data collection? Will case managers have a clinical role in managing patients' progress on the pathway? Although the answers to these questions have varied among successful pathway programs, most authors urge that physicians be as involved as possible, and all authors of reports on critical pathways have noted the importance of clearly defining staff roles before the pathways are implemented [23, 27-29].
Concerns about Critical Pathways
Autonomy versus Standardization
A common response of physicians to critical pathways is to view them as another manifestation of “cookbook medicine” [43-45]. However, although critical pathways encourage standardization as a strategy to improve quality and efficiency, physicians may gain even greater control over the care of their patients by helping define these standards.
Most institutions rely on the physician to judge when the individual needs of a patient require a different course of action. At any time, physicians at our institution can and do write orders that change the pathway for a patient or remove a patient from a pathway completely. Critical pathways are thus used as tools to increase control over patient care rather than as blunt instruments to constrain clinical judgment in an effort to control costs.
Finding the proper balance between autonomy and standardization may prove to be elusive. An open search for this balance, however, involving a continuing dialogue among clinicians and the institution, should lie at the heart of any successful critical pathways program.
Malpractice Risk
Another frequently voiced concern is that physicians may be more vulnerable to malpractice suits if they do not comply with a critical pathway and a patient has a complication. Practice guidelines have been used more often to implicate than to exonerate defendant physicians, and institutions may incur greater liability when they authorize the use of a critical pathway [46, 47]. However, the use of critical pathways cuts both ways: Attorneys surveyed in one study reported that the existence of guidelines in certain cases had induced them not to bring suit in the first place [48], and other attorneys have described several ways in which critical pathways can decrease overall malpractice risk [47]. Many malpractice suits reach trial because of disagreement over what the standard of care should have been for the patient. Such disagreement is less likely to occur with critical pathways. By establishing a management protocol that has been reviewed by local opinion leaders, a critical pathway identifies the appropriate standard of care and helps keep the caregivers' attention focused on the most vital steps. Furthermore, because documentation is such an important aspect of pathways, if the physicians' management deviates from that suggested by the pathway, the reason behind the deviation is also carefully documented.
Research and Education
The research and educational missions of teaching hospitals are already in jeopardy, and critical pathways may seem to further undermine training by discouraging experimentation and independent thinking by trainees. Those responsible for housestaff education may feel that critical pathways set forth given processes of care that stifle the questioning through which residents learn.
On the other hand, medical training may be well served by incorporating methods such as critical pathways to teach students about cost-effective practice. At our institution, we have incorporated critical pathways into our teaching programs by involving housestaff in all phases of pathway development and implementation. We have also used the pathways themselves as teaching instruments in lectures that explore the clinical controversies of pathways. These activities have helped many members of the housestaff overcome the natural resistance they have for clinical “protocols” and have smoothed the integration of pathways into our teaching hospital.
Physicians who do clinical research may be concerned that strong institutional support will create an atmosphere in which patients will be steered away from clinical research studies into treatment according to critical pathways. Critical pathways, however, are not meant to supplant clinical research but rather to improve the “usual care” that is delivered. For example, one critical pathway at our institution includes explicit instructions to consider patients for a clinical research protocol and to contact the research team when appropriate. We have also encouraged the pathway development teams to think of research questions that may be embedded within their pathways, the answers for which may be discovered during the implementation of the pathway—for example, during variance analysis.
Effectiveness of Critical Pathways
Despite the rapid implementation of critical pathway programs, uncertainty persists about their effectiveness. As mentioned previously, the only published controlled study on a critical pathway found that pathways have no effect on the duration of the hospital stay or on patient outcomes [13]. In addition, we are aware of no studies that have attempted to measure the costs of pathway development, implementation, and maintenance. It has also been suggested that the improvements that some authors have attributed to critical pathways could have been achieved just as easily by simply instructing clinicians to manage their patients within a specified target duration of stay [27].
However, many hospitals have concluded that the competitive environment will not allow them to wait for the results of rigorous trials before pursuing critical pathways. Furthermore, performing controlled trials may prove to be difficult because of “contamination” of any control group with knowledge of the intervention. Studies in which patients or physicians are randomly assigned to either a pathway or conventional management are therefore not likely to be undertaken.
To measure the effectiveness of pathways in reducing costs, one must also measure costs for the entire episode of care, including not only the hospital phase but also any prehospital or posthospital care associated with the condition. Critical pathways that reduce hospital costs by merely shifting equal or more costs into the outpatient setting do not meet the true needs of patients or the health care system.
Even if valid data on resource use, patient satisfaction, and outcomes can be gathered, the effectiveness of critical pathways at an institution may remain a value judgment. What would happen, for instance, if a hospital implemented a pathway for acute chest pain and found out that duration of the hospital stay and overall costs were reduced, but that patients were now more likely to return to the emergency department with recurrent pain, or were less satisfied with their care? Would the hospital change its pathway, and if so, how? Unfortunately, the cost, quality, and satisfaction vectors may not always point neatly in the same direction. What values are placed on these different outcomes of critical pathways is an issue each institution needs to consider closely, with physicians as active participants in all such decision making.
Conclusion
Critical pathway initiatives are being launched throughout the United States. As a potential tool of quality improvement, critical pathways have tremendous appeal because of their multidisciplinary methods, their focus on process and on reducing unnecessary variation, and their attention to patient outcomes—all in a package that also offers a tangible way to reduce the duration of hospital stays and resource use. However, despite the appealing logic of this approach to quality improvement, serious concerns and questions remain about the development, implementation, and costs of critical pathways, as well as about their true potential to reduce costs or improve quality.
Methods to develop critical pathways remain unstudied and are still evolving, with wide variations seen among institutions in their approach to topic selection, team composition, documentation of current care processes, and the evaluation of the medical literature and other external benchmarks. Differences in the pathway development process underscore the striking differences reported among critical pathway formats and the strategies to implement pathways and gather variance data. Considerable research is needed to explore which methods of pathway development and implementation are most likely to provide benefits. Measuring the costs of critical pathways and their impact on outpatient resources is essential to helping physicians and health care organizations determine whether such programs are truly worth the effort. As the technology of critical pathways and their setting evolve, an important challenge for investigators will be to develop methods to evaluate pathway techniques and their impact.
While future research is pursued, critical pathway programs are in place today, affecting the care of thousands of patients daily. An important current challenge for physicians is to participate in pathway development and implementation so that the management protocols reflect their beliefs about care. Although critical pathways clearly hold the promise of reduced costs and improved quality, the fulfillment of this promise requires the full and informed participation of physicians.

Clinical Path to treating Acute Childhood Leukemia

(2010 Edition)

Acute Childhood Leukemia and its Standardized
Clinical Pathway
Suitable Targets
Patients diagnosed with Acute Childhood Leukemia (ICD-10:C91.0).
Clinical Symptoms
Physical examination: high body temperature, white skin membranes, scar-like patches on skin,
Enlarged lymph nodes, stuffy chest, etc.
Blood testing based on standard measures
Bone marrow check
Examination of immune system
Genetics overview using DNA analysis and FISH (when necessary)
Genetics studies based on Leukemia
Categorization of various High-risk groups
Standard risk group: must meet all of the following criteria
Age of patient is between 1 and 10
WBC count is less than 50 x 109 /L
Non-T-ALL
Non-immature B-ALL
No t (9;22) or BCR/ABL infused genes
No t (4;11) or MLL/AF4 infused genes
No t (1;19) or E2A/PBX1 infused genes
In most cases the cancer cells form a tumor. But some cancers, like leukemia, rarely form
tumors. Instead, these cancer cells are in the blood and bone marrow.
When cancer cells get into the bloodstream or lymph vessels, they can travel to other
parts of the body. There they begin to grow and form new tumors that replace normal
tissue. This process is called metastasis (muh-tas-tuh-sis).
No matter where a cancer may spread, it is always named for the place where it started.
For instance, breast cancer that has spread to the liver is still called breast cancer, not
liver cancer. Likewise, prostate cancer that has spread to the bone is called metastatic
prostate cancer, not bone cancer.
Different types of cancer can behave very differently. For example, lung cancer and
breast cancer are very different diseases. They grow at different rates and respond to
different treatments. That is why people with cancer need treatment that is aimed at their
own kind of cancer.
Not all tumors are cancerous. Tumors that aren't cancer are called benign (be-nine).
Benign tumors can cause problems – they can grow very large and press on healthy
organs and tissues. But they cannot grow into other tissues. Because of this, they also
can't spread to other parts of the body (metastasize). These tumors are almost never life
threatening.
What are the differences between cancers in
adults and children?
The types of cancers that develop in children are different from the types that are found in
adults. In most cases, childhood cancers tend to respond better to chemotherapy. That's
because these cancers are growing quickly, and most forms of chemotherapy target cells
that are growing fast. But because chemotherapy can have some long-term side effects,
children who survive their cancer need careful attention for the rest of their lives.
Children with cancer and their families have special needs that are best met by children's
cancer centers. Treatment in these centers offers them the advantage of a team of experts
with experience in treating children. The team can include (besides doctors and nurses)
psychologists, social workers, child life specialists, educators, and others.
In the United States, most children with cancer are treated at a pediatric cancer center that
is a member of the Children's Oncology Group (COG). All of these centers are part of a
university or a children's hospital. As we have learned more about treating childhood
cancer, it has become even more important that treatment be given by experts in these
diseases.
What is childhood leukemia?
Leukemia is a cancer of the blood-forming cells. Most of time, it is a cancer of the white
blood cells, but some leukemias start in other kinds of blood cells. Leukemia starts in the
bone marrow, where the blood cells are made, and quickly spreads to the blood. From
there it can go to the lymph nodes, spleen, liver, central nervous system, and other
organs.
In contrast, some other types of cancer, such as Wilms tumor (a kidney cancer), can start
in other organs and then spread to the bone marrow (or elsewhere). But those cancers are
not leukemia.
Normal bone marrow, blood, and lymphoid tissue
To understand the different types of leukemia, it helps to know something about the
blood and lymph systems.
Bone marrow
Bone marrow is the soft, spongy, inner part of bones. It is where all new blood cells are
made. In babies, bone marrow is found in nearly all of the bones of the body. But by the
teenage years it is found mostly in the flat bones such as those of the skull, shoulder
blades, ribs, pelvis, and back bones.
Bone marrow is made up of a small number of blood-forming cells (blood stem cells),
other early forms of blood cells, fat cells, and tissues that help the blood cells grow. Early
blood cells can grow to become red blood cells, white blood cells, or platelets.
Red blood cells
Red blood cells carry oxygen from the lungs to all other tissues of the body and take
carbon dioxide back to the lungs to be removed. A shortage of red blood cells (called
anemia) causes weakness, shortness of breath, and tiredness.
Platelets
Platelets are actually pieces that break off from certain bone marrow cells. Platelets help
stop bleeding by plugging holes in blood vessels caused by cuts or bruises. A person with
too few platelets may bleed and bruise easily.
White blood cells
White blood cells (also called leukocytes) help defend the body against germs. There are
quite a few types (and subtypes) of white blood cells. Each has a special role to play in
protecting the body against infection. The 3 main types of white blood cells are
lymphocytes, granulocytes, and monocytes.
Lymphocytes: Lymphocytes are the main cells that make up lymphoid tissue, a
major part of the immune system. The immune system helps the body fight off
infections. More information about the lymphocytes is given below.
Granulocytes: The main job of granulocytes is to destroy germs. Granulocytes go
through several changes as they grow from early cells to mature, infection-
fighting cells.
Monocytes: Monocytes are also important in protecting the body against germs.
After a short time in the bloodstream, they enter tissues to become macrophages,
which can destroy some germs by surrounding and "eating" them.
Lymphoid tissue
Lymphoid tissue is the main part of the immune system. Lymphoid tissue is found in
many places throughout the body including lymph nodes, the thymus, the spleen, the
tonsils and adenoids, and the bone marrow. It is also scattered within other systems such
as the digestive system.
The main cell type that forms lymphoid tissue is the lymphocyte. These are the cells from
which acute lymphocytic leukemia (ALL) develops. The 2 main types of lymphocytes
are:
B lymphocytes (or B cells)

??T lymphocytes (or T cells)
Although both can develop into leukemia, B-cell leukemias are much more common than
T-cell leukemias.

Normal T cells and B cells do different jobs within the immune system. For the most part,
B cells help protect the body mainly against bacteria, while T cells help protect against
foreign substances and viruses. Some T cells act as a check on the immune system to
make sure it does not attack normal cells.

Types of leukemia in children

Leukemia can be either fast growing (acute), or slower growing (chronic). Almost all
leukemia in children is acute.

Acute leukemias

There are 2 main types of acute leukemia:

? Acute lymphocytic leukemia (ALL), also called acute lymphoblastic leukemia,
accounts for about 3 out of 4 cases of childhood leukemia. This leukemia starts from
the lymphoid cells in the bone marrow.

? Acute myelogenous leukemia (AML), also called acute myeloid leukemia, accounts
for most of the remaining cases. This leukemia starts from the cells that form white
blood cells (other than lymphocytes), red blood cells, or platelets.

Hybrid or mixed lineage leukemias are rare. The cells have features of both ALL and
AML. They are most often treated like ALL and respond to treatment like ALL.

Chronic leukemias

Chronic leukemia is also divided into 2 types, but these forms of leukemia are rare in
children. They are not covered here. If you need information on these, please call us for a
copy or go to our Web site to read Leukemia: Chronic Myeloid (Myelogenous) or
Leukemia: Chronic Lymphocytic.

Juvenile myelomonocytic leukemia (JMML)

This rare type of leukemia is neither chronic nor acute. It isn't as fast growing as acute
myelogenous leukemia or as slow as chronic myeloid leukemia. It occurs most often in
young children (under age 4). Symptoms can include pale skin, fever, cough, trouble
breathing (due to too many white blood cells in the lungs), and a swollen spleen and
lymph nodes.

How many children get leukemia?

Leukemia is the most common cancer in children and teens. It accounts for about 1 out of
3 of cancers in children. Even so, childhood leukemia is a rare disease.

Acute lymphocytic leukemia (ALL) accounts for about 3 out of 4 the leukemia cases
among children and teens. Most of the rest of the cases will be acute myelogenous
leukemia (AML). Chronic leukemia is rare in children.

ALL is most common in early childhood, peaking between 2 and 4 years of age. Cases of
AML are more spread out across the childhood years, although it is slightly more
common during the first 2 years of life and during the teenage years.

What causes childhood leukemia?

The exact cause of most cases of leukemia is not known. But doctors have found that this
cancer is linked to a few risk factors.

A risk factor is something that increases a person's chance of getting a disease. Different
cancers have different risk factors. Some risk factors, such as smoking, can be controlled.
Others, like a person's age or family history, can't be changed. But risk factors don't tell
us everything. Having a risk factor, or even several risk factors, does not mean that you
will get the disease. And many people who get the disease may not have had any known
risk factors. It is important to remember that most children with leukemia do not have any
known risk factors, and the cause of their cancer is not known at this time.

Genetic risk factors

Genetic risk factors are those that are part of our DNA. DNA is the substance that carries
the instructions for nearly everything our cells do. While we don't know the exact cause
of most cases of leukemia, during the past few years scientists have made great progress
in learning how certain changes in DNA can cause bone marrow stem cells to develop
into leukemia. But while some genetic factors increase the risk of childhood leukemia,
most cases of leukemia are not linked to any known genetic causes.

Certain genetic conditions such as Li-Fraumeni syndrome, Down syndrome, Klinefelter
syndrome, and others also carry an increased risk of leukemia. (A syndrome is a cluster
of signs and symptoms that point to a certain disease or disorder.) Other genetic diseases

that cause children to be born with an abnormal immune system may also increase their
risk of getting leukemia.

Brothers and sisters of children with leukemia have a slightly higher chance of getting
leukemia, although the overall risk is still low. The risk is higher among identical twins.
If an identical twin develops childhood leukemia, the other twin has about a 20% chance
of getting leukemia as well. This risk is even higher if the leukemia starts in the first year
of life.

Having a parent who develops leukemia as an adult does not seem to raise a person's risk
of leukemia.

Lifestyle risk factors

For the most part, lifestyle risk factors such as diet and exercise play a minor role in
childhood cancer risk, even though they are important in adult cancers. Some studies
have suggested that a mother drinking a lot of alcohol during pregnancy may increase the
risk of leukemia in her child, but not all studies have found such a link.

Environmental risk factors

Environmental risk factors are things around us such as radiation and certain chemicals,
which increase the risk of getting diseases like leukemia.

Radiation

Exposure to high levels of radiation is a risk factor for childhood leukemia. Japanese
atomic bomb survivors had a much higher risk of getting AML. There may also be some
risk if a fetus is exposed to radiation within the first months of pregnancy, although the
extent of the risk is not clear.

It is not known how much risk their might be when children are exposed to lower levels
of radiation, such as from x-rays or CT scans. Any risk increase is likely to be small, but
to be safe, most doctors do not order these tests for pregnant women or children unless
they are really needed.

Exposure to chemo drugs and certain other chemicals

Children and adults who were treated with chemo for other cancers have a higher risk of
getting a second cancer such as AML later in life. These leukemias usually develop
within 5 to 10 years of treatment and tend to be hard to treat.

Exposure to chemicals like benzene (a solvent used in the cleaning industry and in the
making of some drugs, plastics, and dyes) may cause AML in adults and, rarely, in
children. Chemical exposure is more strongly linked to an increased risk of AML than to
ALL.

Some studies have found a possible link between childhood leukemia and household
exposure to pesticides, either during pregnancy or early childhood. More research is
needed to try to confirm these findings.

Weakened immune system

Patients who are taking drugs to suppress their immune systems (mainly organ transplant
patients) have a higher risk of getting certain cancers, such as lymphoma and ALL.

Other possible risk factors

A few studies have suggested that some childhood leukemias may be caused by a
combination of genetic and environmental factors. For example, certain genes normally
control how our bodies break down and get rid of harmful chemicals. Some people have
different versions of these genes that make them less effective. Children who inherit these
genes may not be as able to break down harmful chemicals if they are exposed to them.
The combination of genetics and exposure might increase their risk for leukemia.

Many other possible risk factors have been studied but, so far, most studies have not
found strong links between any other risk factors and childhood leukemia.

Can leukemia be prevented?

Right now there is no known way to prevent most cases of leukemia. Unlike some other
types of cancer, leukemia is usually not linked to lifestyle risk factors. Children with a
higher risk of leukemia (such as those who have Li-Fraumeni syndrome or Down
syndrome) should have careful medical exams by their doctor.

For some people, treatment with chemo or radiation for other, earlier cancers may cause
leukemia later on. But the clear need to treat life-threatening diseases with chemo,
radiation therapy, or organ transplant must be balanced against the small chance of
developing leukemia several years later.

Because the cause of most cases of leukemia is not known, parents of children with
leukemia need to know that there is nothing they could have done to prevent this illness.

How is leukemia found?

At this time, there are no special tests used to help find leukemia early. The best way to
find the disease early is for the parents to call the doctor right away if they notice that
their child has any of the symptoms listed below.

Close follow-up is important for children who have been treated with chemo or radiation
therapy for an earlier cancer, children who have certain genetic conditions, and children
who have had organ transplants. These children are at greater risk for certain types of
leukemia.

The exams and tests below are used to find the disease, measure how advanced it may be,
and help decide what type of leukemia it is. That way, treatment can be tailored to
provide the best chance of success.

Signs and symptoms of childhood leukemia

Most of the signs and symptoms of leukemia result from a lack of normal blood cells.
This happens because the cancer cells crowd out the normal cells that make blood in the
bone marrow. The leukemia cells may spread to other parts of the body, which can cause
also symptoms. Keep in mind that many of the symptoms listed here most often are
caused by other problems – not leukemia.

Tiredness (fatigue) and pale skin: A child may be very tired, weak, dizzy, pale, or short
of breath. These problems are caused by a shortage of red blood cells called anemia.

Infections and fever: A child with leukemia may have a high fever and an infection that
doesn't get better with antibiotics. This can happen because there are not enough normal
white blood cells to fight the infection. Although children with leukemia may have very
high white blood cell counts, the cells are not normal and may not protect against
infection the way they should.

Easy bleeding or bruising: A child with leukemia may bruise easily or have increased
bleeding from small cuts or nosebleeds. There may be small red spots on the skin caused
by bleeding from tiny blood vessels. The bleeding is caused by a lack of blood platelets,
which are needed to plug holes in blood vessels.

Bone or joint pain: Some children will have bone pain, and a smaller number will have
joint pain. This is from the build-up of leukemia cells near the surface of the bone or
inside the joint.

Swelling of the belly (abdomen): Leukemia can cause the liver or spleen to get larger.
The doctor can feel this swelling.

Loss of appetite and weight loss: If the spleen or the liver becomes large enough, it may
press against other organs like the stomach. This can limit the amount of food that can be
eaten, leading to a loss of appetite and weight loss over time.

Swollen lymph nodes: Leukemia can spread to lymph nodes causing them to swell. The
child, a parent, or a doctor or nurse might notice swollen nodes on the sides of the neck,
in the groin, in the underarm area, or above the collarbone. Swelling of the lymph nodes
inside the chest or abdomen (belly) is usually found by tests such as CT or MRI scans.
(An enlarged lymph node in a child is more often a sign of an infection than leukemia,
but it should be checked by a doctor and followed closely.)

Coughing or trouble breathing: The T-cell type of acute lymphocytic leukemia (ALL)
often involves the thymus gland, which is found in the chest near the heart. Enlargement
of the thymus or of lymph nodes inside the chest can press on the nearby windpipe. This
can lead to coughing or trouble breathing.

Swelling of the face and arms: A large vein that carries blood from the head and arms
back to the heart passes next to the thymus. Growth of the leukemia cells may press on
this vein, causing the blood to "back up" in the veins. This can lead to swelling and
bluish-red discoloration of the head, arms, and upper chest. It can also cause headaches,
dizziness, and a change in consciousness if it affects the brain. This is known as SVC
syndrome. Patients with this problem need to see a doctor right away.

Headache, seizures, or vomiting: Leukemia cells can spread outside the bone marrow
into the central nervous system (brain and spinal cord), causing headaches, trouble
thinking, weakness, seizures, vomiting, problems with balance, and blurred vision. It can
spread to other organs as well.

Rashes or gum problems: Cancer cells can spread to the gums, causing swelling, pain,
and bleeding. Spread to the skin can cause spots that look like rashes.

Extreme tiredness and weakness: One rare but very serious symptom of AML is
extreme tiredness, weakness, and slurring of speech. This can happen when very high
numbers of leukemia cells make the blood too thick and reduce the flow of blood to the
brain.

Tests used to find leukemia

Most of the symptoms of leukemia are common and can be caused by something other
than cancer. The doctor will want to do certain tests to find out if cancer is present and, if
so, what type of leukemia it is.

Medical history and physical exam

The doctor will want to get a complete medical history, including how long your child
has had symptoms and whether or not your child has any risk factors. A family history of
cancer, especially leukemia, may also be important.

The physical exam will likely focus on any swollen lymph nodes, areas of bleeding or
bruising, or signs of infection. A full exam of the nervous system may also be done. The
child's eyes and mouth will likely be looked at carefully. The doctor will feel the belly for
signs of a swollen spleen or liver.

If there is any reason to think there might be problems caused by abnormal numbers of
blood cells (anemia, infections, bleeding or bruising, etc.), the doctor will likely get a
blood sample to check your child's blood counts. If these are not normal, the doctor may
refer you to a childhood cancer doctor, who may run one or more of the tests described
below.

Types of samples used to test for leukemia in children

Blood cell counts: Blood tests will be done on blood drawn from a vein or from a "finger
stick." Most children with leukemia will have too many white cells in their blood and not
enough red blood cells or platelets. Also, the white blood cells will be blasts, an early

type of blood cell normally found in the bone marrow but not in the blood. Changes in
the numbers of different cell types and how these cells look under the microscope often
make the doctor suspect leukemia. But usually a sample of bone marrow will need to be
taken to be certain.

Bone marrow samples: Bone marrow samples are taken by doing a bone marrow
aspiration and biopsy – 2 tests that are usually done at the same time. The samples are
most often taken from the back of the pelvic (hip) bone, although in some cases they may
be taken from the breastbone or other bones.

This test involves removing small amounts of bone marrow from the bone with thin
needles. The samples are sent to the lab to see if cancer cells are present. This test is also
used later to see if the leukemia is responding to treatment.

For this test, the area around the bone is numbed and the child may be given a drug to
reduce pain or be asleep during the test. Once the biopsy is done, pressure will be applied
to the site to help prevent any bleeding

Spinal tap (lumbar puncture): This test is done to look for leukemia cells in the liquid
around the brain and spinal cord (cerebrospinal fluid or CSF). It can also be used to put
chemo into the CSF to keep the cancer from spreading there.

For this test, the doctor first numbs an area in the lower part of the back over the spine.
The doctor may also give the child medicine to make him or her sleep during the test. A
small needle is placed between the bones of the spine to draw out some cerebrospinal
fluid (CSF). The fluid is checked for leukemia cells. It is important that someone who is
an expert does this test. If the spinal tap isn't done right and some blood leaks into the
spinal fluid, leukemia cells could get into the spinal fluid and grow there.

Lymph node biopsy: For this test, a whole lymph node is removed. If the node is near
the skin's surface, this is a simple operation. But it may be more complex if the node is
inside the chest or belly. Most often the child will need general anesthesia (drugs are used
to put the child into a deep asleep). This test is rarely needed for children with leukemia.

Lab tests for leukemia

A doctor with special training in lab tests (a pathologist) will look at all of the biopsy
samples (bone marrow, lymph node tissue, blood, and cerebrospinal fluid) under a
microscope. The doctor looks at the size and shape of the cells as well as other features to
classify the cells into specific types.

A key factor is whether or not the cells look mature. Leukemia cells do not have the
features of normal blood cells and do not work well in fighting infections. The most
immature cells are called blasts.

There are also a number of very precise lab tests the doctor might use to diagnose and
classify leukemia. You might hear some of the following terms used: cytochemistry,
cytogenetics, flow cytometry, FISH, and immunohistochemistry. These tests are
explained in detail our document Childhood Leukemia.

Other blood tests: If the child does have leukemia, other blood tests will be done to
measure certain chemicals in the blood to see how well the liver and kidneys are working.
Tests may also be done to check for infections so they can be treated right away.

Imaging tests

Imaging tests are ways of taking pictures of the inside of the body. Some of these tests
might be done in children with leukemia to get a better idea of the extent of the disease.

Chest x-rays: A chest x-ray can tell if the thymus or lymph nodes are swollen. In can
also help to find pneumonia if the child appears to have an infection.

CT (computed tomography) scans: CT scans (sometimes called "CAT" scans) are
special kinds of x-rays in which a beam moves around the body, taking pictures from
different angles. This test can help tell if the leukemia has spread into lymph nodes in the
chest or to organs like the spleen or liver.

Instead of taking one picture, like a regular x-ray, a CT scanner takes many pictures as it
rotates around your child. A computer then combines these pictures into detailed pictures
of the part of the body that is being studied.

Often after the first set of pictures is taken, your child may get an injection of a contrast
dye (it is put into a vein) or be asked to drink a solution of contrast liquid. This helps
better outline blood vessels and internal organs. A second set of pictures is then taken.
CT scans take longer than regular x-rays. Your child will need to lie still on a table while
it slides in and out of the scanner. Some children may need to be sedated before the test.

Spiral CT (also known as helical CT) is now used in many medical centers. This type of
CT scan uses a faster machine.

PET/CT scan: In recent years, newer machines have been made that combine the CT
scan with a PET (positron emission tomography) scan. For a PET scan, a form of sugar
that contains a radioactive atom is injected into the blood. Because cancer cells in the
body grow quickly, they absorb large amounts of the special sugar. A camera can then
spot a picture of areas of radioactivity in the body. The PET/CT scan combines the 2
pictures to give the doctor more details about any areas of cancer.

MRI (magnetic resonance imaging): An MRI is like a CT scan except that magnets and
radio waves are used to make the pictures instead of x-rays. MRI scans are helpful in
looking at the brain and spinal cord.

MRI scans take longer than CT scans – often up to an hour. Your child may have to lie
inside a narrow tube, which can be hard for some children. Drugs are sometimes needed
to help them sleep for this test. Newer, more open MRI machines may be another option.
The MRI machine makes loud buzzing noises and clicks that may scare your child. Some
places provide headphones to block this out.

Ultrasound: Ultrasound uses sound waves to make a picture of the inside of the body.
Ultrasound can be used to look for enlarged organs inside the belly. This is an easy test to

have done. Your child simply lies on a table, and a technician moves a sort of wand over
the part of the body being looked at.

Gallium scan and bone scan: These scans can be useful if the child has bone pain that
might be caused by infection or cancer in the bones. They are done in a way much like
PET scans. If the child has already been found to have leukemia or if a PET scan has
already been done, there is no need for these scans.

After the tests: Classification

For most cancers, staging is the process of finding out how advanced the cancer is. Most
types of solid cancers are staged based on the size of the tumor and how far the cancer
has spread from the place where it started.

But leukemia is not staged like most other cancers. The cancer already involves the bone
marrow and blood, so leukemia cells are already throughout the body. The major concern
is whether the leukemia cells have also started to collect in other organs such as the liver,
spleen, lymph nodes, or central nervous system (brain and spinal cord). For example, if
the cancer cells have spread to the central nervous system in large numbers, they can be
seen under a microscope in samples of the cerebral spinal fluid (CSF), the fluid that
surrounds the brain and spine. Then treatment will need to be more intense in order to kill
these cells.

The most important factor for leukemias is figuring out the type (ALL vs. AML) and
subtype of the leukemia. This is done by testing samples of the blood, bone marrow, and
sometimes lymph nodes or CSF. Deciding upon the exact type and subtype of leukemia is
a complex process that can be difficult even for doctors to understand. For more
information, please see Childhood Leukemia.

Prognostic factors are important in helping the doctor decide whether to use standard
treatment or more intense treatment. These factors refer to certain differences seen among
patients with good versus poor response to treatment. Prognostic factors seem to be more
important in ALL than in AML.

Acute lymphocytic leukemia (ALL)

There are 4 main subtypes of ALL. They are:

Early Pre-B cell

Pre-B cell

Mature B cell

T cell

Prognostic factors for children with acute lymphocytic leukemia (ALL)

Prognostic factors (differences among patients that affect how they respond to treatment)
are used to help tell what risk group a child may fall into. In one of the more common
systems, children with ALL are divided into standard-risk, high-risk, or very high-risk
groups. The higher-risk groups are given more intense treatment. As a rule, children in
lower-risk groups have a better outlook than those at very high risk.

There are many prognostic factors used in ALL, but these 2 are the most important. Keep
in mind that many children with one or more poor factors can still be cured

Age: Children with B-cell ALL between the ages of 1 and 9 tend to do better.
Children younger than 1 and children older than 10 years are at higher risk. The
outlook in T-cell ALL isn't affected much by age.

White blood cell count (WBC): Children who have very high white cell counts
(greater than 50,000 per cubic millimeter) when the leukemia is found need more
intense treatment.

Acute myelogenous leukemia (AML)

AML has several subtypes, based on the type of cell involved and how mature it is.
Although lab tests can help diagnose AML, the subtypes of AML are classified mainly by
how they look under the microscope. It may also be useful to look for changes in the
genes or chromosomes of the leukemia cells. There are 8 subtypes of AML labeled M0 to
M7.

Prognostic factors for children with AML

Prognostic factors do not seem quite as important for AML as they are for ALL. These
factors can include the white blood cell count, certain changes in chromosomes, how the
cancer cells look under a microscope, whether the leukemia is a result of treatment for
another cancer, and how quickly the leukemia responds to treatment.

Hybrid or mixed leukemias

These leukemias have cells with features of both ALL and AML when they are looked at
in the lab. In children, these leukemias are generally treated like ALL and respond to
treatment like ALL.

Survival rates for childhood leukemia

Some people with cancer may want to know the survival rates for their type of cancer.
Others may not find the numbers helpful, or may even not want to know them. Whether
or not you want to read about survival rates is up to you.

The 5-year survival rate refers to the percentage of children who live at least 5 years after
their cancer is found. Of course, many children live much longer than 5 years.

With regard to acute leukemias, children who are free of disease after 5 years are very
likely to have been cured, as it very rare for these cancers to return after such a period of
time.

The 5-year survival rate for ALL in children has greatly increased over time and is now
more than 80% overall. But current 5-year survival rates are based on children first
diagnosed and treated more than 5 years ago. Improvements in treatment since then may
mean an even better outlook for children treated today.

The 5-year survival rate for children with AML has also increased over time, and is now
in the range of 50% to 70%. However, survival rates can vary depending on the subtype
of AML. For instance, most studies suggest that the cure rate for acute promyelocytic
leukemia (APL), a subtype of AML, is now higher than 80%.

Of course, the outlook for each child is different, depending on a number of things such
as the prognostic factors. Talk with your cancer care team if you have questions about
your child's chances of a cure. They know the situation best.

How is childhood leukemia treated?

This information represents the views of the doctors and nurses serving on the American Cancer Society's
Cancer Information Database Editorial Board. These views are based on their interpretation of studies
published in medical journals, as well as their own professional experience.

The treatment information in this document is not official policy of the Society and is not intended as
medical advice to replace the expertise and judgment of your cancer care team. It is intended to help you
and your family make informed decisions, together with your doctor.

Your doctor may have reasons for suggesting a treatment plan different from these general treatment
options. Don't hesitate to ask him or her questions about your treatment options.

About treatment

After leukemia is found your child's cancer care team will talk to you about treatment
options. The most important factor in choosing a treatment is the type of leukemia,
although other factors also play a role.

The main treatment for childhood leukemia is chemotherapy (chemo). Other treatments
such as surgery and radiation treatment may be used in some cases.

Your doctor should make sure that your child's treatment reflects his or her risk group.
Your child should be treated according to a set of instructions called a protocol from the
National Cancer Institute (NCI) or a cooperative study group. This will ensure the most
up-to-date treatment for your child. And be sure to ask your doctor about any side effects
your child might have from treatment. Many parents find it helpful to bring a note pad or
a tape recorder when they talk to the doctor.

Be sure to tell your child's doctor about any drugs, herbal remedies, or other things you
might be giving your child. These could affect how well the treatment works.

This section contains general comments about types of treatments used for childhood
leukemia, followed by a discussion of treatment options based on the type of leukemia.

Immediate treatment

Some children are very ill when they are found to have leukemia. Low blood counts can
result in serious problems such as infections, bleeding, and even heart failure. Antibiotics,
other drugs, and blood transfusions may be needed to treat or prevent some of these
problems before the leukemia is treated.

Surgery

Unlike most other cancers, surgery has only a small role in the treatment of leukemia.
This is because leukemia is a disease of blood and bone marrow and cannot be cured with
surgery.

Surgery may be used to help give treatment. A plastic tube may be placed into a large
vein. The tube, called a central venous catheter (CVC) or a venous access device (VAD),
allows medicines to be given and blood samples to be removed without the need for
repeated needle sticks. The end of the tube stays just under the skin or sticks out in the
chest area or upper arm. It is important for parents to learn how to care for the VAD.

In cases where a boy with leukemia has a relapse of the disease in a testicle, surgery may
be done to remove the testicle (along with giving chemo to treat the rest of the body).

Radiation treatment

Radiation therapy is the use of high-energy radiation to kill cancer cells. For children
with acute leukemia, radiation might be used to try to prevent or treat cancer in the brain
or in the testicles. It can also be used, though rarely, in an emergency to shrink a tumor
that is putting pressure on the windpipe. But chemo is often used instead since it may
work faster.

Radiation to the whole body is often an important part of treatment before a bone marrow
or peripheral blood stem cell transplant (see the section, "Bone marrow or peripheral
blood stem cell transplant (SCT)").

Chemotherapy

Chemo refers to the use of drugs to kill cancer cells. Usually the drugs are given either
into a vein, into the cerebrospinal fluid (CSF), or as a pill. Once the drugs enter the
bloodstream, they spread throughout the body. Chemo is the main treatment for nearly all
types of leukemia. Children might get several drugs at different times during the course
of treatment.

Doctors give chemo in cycles, with each cycle of treatment followed by a rest period. As
a rule, AML treatment will involve higher doses of chemo over a shorter period of time,
while ALL will involve the use of lower doses over a longer period of time (perhaps 2 to
3 years).

Immediate side effects

While chemo drugs kill cancer cells, they can also damage normal cells. This happens
because they are aimed at cells that are growing quickly such as cancer cells. But in the
process they also damage other fast-growing cells. The lining of the mouth and intestines,
hair, and blood cells all grow quickly and are likely to be damaged by chemo, which can
lead to the following side effects:

Diarrhea

Nausea and vomiting

Increased risk of infections (because of low white blood cell counts)

Bruising and bleeding easily (from low platelet counts)

Tiredness (caused by low red blood cell counts)
These side effects usually go away after treatment ends. And there are often ways to
manage these side effects during treatment. For example, there are drugs that can be
taken to prevent or reduce nausea and vomiting. Drugs known as growth factors are
sometimes given to keep blood counts higher and reduce the chance of infection.

Tumor lysis syndrome can be a side effect of chemo. When large numbers of leukemia
cells are killed, they break open and release their contents into the bloodstream. This can
affect the kidneys, heart, and nervous system. Giving the child extra fluids or certain
drugs that help rid the body of these toxins can help prevent this problem.

Some side effects depend on which drugs are used. Be sure to ask your child's doctor or
nurse about any specific side effects you should watch for and about what you can do to
help reduce them.

Long-term side effects

Possible long-term effects of chemo are described in the section, "Moving on after
treatment."

Targeted therapy

In recent years, new drugs that are aimed at certain parts of cancer cells have been
developed. These are called targeted drugs. They work differently than standard chemo
drugs. They often have less severe side effects. Some of these drugs may be useful in
certain cases of childhood leukemia.

These drugs are taken daily as pills. Possible side effects include diarrhea, nausea, muscle
pain, fatigue, and skin rashes. Often these side effects are mild. A common side effect is
swelling around the eyes or in the hands or feet.

High-dose chemotherapy and stem cell transplant

Stem cell transplant (SCT) can sometimes be used for children whose chances of survival

are poor with standard or even intense chemo. SCT allows doctors to use very high doses
of chemo. The high doses of these drugs destroy the bone marrow, which keeps new
blood cells from being made. This poses a threat to the child's life. But after treatment is
finished, the child gets a transplant of blood-forming stem cells to replace the bone
marrow. Stem cells are very early cells that are able to make new blood cells.

Types of transplants

There are 2 main types of stem cell transplants: allogeneic and autologous. The
difference is the source of the blood-forming stem cells.

Allogeneic SCT: For childhood leukemia, the blood-forming stem cells most often come
from another person. This is called an allogeneic stem cell transplant.

Usually the donor is a brother or sister but, rarely, the donor could be an unrelated
volunteer. Stored cells from umbilical cord blood have also been used for unrelated donor
transplants. These stem cells come from blood drained from the umbilical cord and
placenta after a baby is born and the cord is cut.

Autologous SCT: In an autologous stem cell transplant, the patient's own stem cells are
removed from his or her bone marrow or bloodstream. They are frozen until after
treatment with chemo and/or radiation and then given back to the patient.

This procedure is rarely used for childhood leukemia, for a couple of reasons. One
concern is that there may be leukemia cells among the stem cells, which could be given
back to the child after treatment. To avoid this, the doctors treat the stored cells with
drugs to try to kill any cancer cells. And leukemia has more of a chance to relapse when
the child's own stem cells are used. So stem cells from a donor are more often used.

When SCT may be used

SCT may be used for children with ALL whose leukemia comes back early after going
into remission. It is less clear whether it should be used if more than 6 months has passed

since the chemo was given. These children will often do well with another round of
standard chemo.

Because AML comes back more often, some doctors recommend SCT for some children
with AML right after they have gone into remission, especially if the child has a brother
or sister who can donate cells. If the cancer comes back after the first round of chemo,
then most doctors will suggest SCT as soon as the child goes into remission again.

In any case, it is important that the patient be in remission before the transplant.
Otherwise, the leukemia is more likely to return.

What SCT involves

Here is how the SCT process works: Stem cells are collected from either the bone
marrow or from the bloodstream. The cells are frozen and stored. The child is then given
very high doses of chemo (and sometimes radiation) to kill the cancer cells. All of the
normal cells in the bone marrow are also killed. After treatment, the stored stem cells are
thawed and given to the child as a blood transfusion. Then the waiting begins as the stem
cells settle in the child's bone marrow and start to grow and make new blood cells. For
the next 3 to 4 weeks the patient is a high risk for serious infections (because of low
white blood cell counts), as well as bleeding (because of low platelet counts).
Transfusions and antibiotics are often used to prevent or treat these problems.

Patients most often stay in the hospital until a certain white blood cell count (called the
ANC) is near 1,000. The child is then seen in an outpatient clinic almost every day for
several weeks.

Stem cell transplant is a complex treatment. If the doctors think that a child with
leukemia might be helped by this treatment, it is important that it be done at a hospital
where the staff has a lot or experience with the procedure.

Stem cell transplant can also be very expensive (costing more than $100,000) and often
involves a long hospital stay. Because it is so costly, parents should be sure to get a
written approval from their insurer if their child is to have this treatment.

Side effects of SCT

Side effects from a stem cell transplant can be divided into early and long-term effects.
Early side effects are about the same as those of any other type of high-dose chemo: low
blood cell counts, nausea, vomiting, hair loss, etc. These side effects are caused by
damage to the bone marrow and other tissues that divide quickly. One of the most
common and serious short-term effects is the increased risk of severe infection.
Antibiotics are often given to try to prevent this. Other side effects, like low red blood
cell and platelet counts, may mean that the patient will need transfusions or other
treatments.

Long-term side effects: Some side effects can go on for a long time. Sometimes they
don't show up until months or even years after the transplant. Long-term side effects
could include the following:

Graft-versus-host disease (see below)

Radiation damage to the lungs

Problems with the thyroid or other hormone-making glands

Problems with fertility

Problems with bone growth
Graft-versus-host disease (GVHD) is a major concern of an allogeneic (donor) stem cell
transplant. It happens when the immune system of the patient is taken over by that of the
donor. The donor immune system then begins to attack the patient's other tissues and
organs.

Symptoms can include severe skin rashes with itching and severe diarrhea. The liver and
lungs may also be damaged. The patient may also become tired and have aching muscles.
If severe enough, the disease can be fatal. Drugs that weaken the immune system are
often given to try to keep GVHD under control.

To learn more about stem cell transplants, see our article Bone Marrow and Peripheral
Blood Stem Cell Transplant. You can find out more about long-term effects in the
section, "Moving on after treatment."

Treatment of children with acute lymphocytic leukemia

The main treatment for children with acute lymphocytic leukemia (ALL) is chemo, which
has 3 phases:

Induction

Consolidation (also called intensification)

Maintenance

Induction

The goal of induction is to bring about a remission. This means that leukemia cells are no
longer found in bone marrow samples, the normal marrow cells return, and the blood
counts become normal. (A remission is not the same as a cure.) Children with ALL are
divided into risk groups to make sure that the correct types and doses of drugs are given.
More than 95% of children with ALL will go into remission after 1 month of treatment.

During induction, frequent trips to the doctor will be needed. Your child may spend some
or much of this time in the hospital. Children with standard-risk ALL often receive 3
drugs for the first month of treatment. A fourth drug is typically added for high-risk

children. All children will need to have spinal taps to put chemo right into the
cerebrospinal fluid (CSF) to try to keep cancer from spreading to the central nervous
system (brain and spinal cord). And some, such as those with T-cell leukemia, high white
blood cell counts, or cancer cells in the CSF, may need radiation to the head, too. This
was more common in the past, but recent studies have found that many children even
with high-risk ALL may not need radiation therapy if they are given more intense chemo.
Doctors try to avoid radiation because, no matter how low the dose, it may cause some
problems in thinking and growth.

Consolidation

The goal of this phase (also called intensification) is to get rid of leukemia cells from
places where they can "hide." This phase lasts about 4 to 8 weeks. Several drugs are used,
depending on the child's risk category. Some children may benefit from a stem cell
transplant at this time.

Maintenance

If the leukemia stays in remission after the first 2 phases of treatment, this last phase,
maintenance chemo, can begin. The total length of therapy for all 3 phases is 2 to 3 years
for most children with ALL. Because boys are at higher risk for relapse than girls, many
doctors favor giving them several more months of treatment.

Treatment of residual disease

All these treatment plans may change if the leukemia hasn't completely disappeared.
Soon after treatment has begun the doctor may check the child's bone marrow to see if
the leukemia is going away. If not, treatment may be increased or given for a longer time.
When the leukemia seems to have disappeared, the doctor may do a special chemical test
to look for leukemia cells. If any are found, then once again, chemo may be increased or
prolonged.

Treatment of recurrent ALL

If a child with ALL relapses (the leukemia comes back after treatment), he or she will
again be treated with chemo. This may include the same or different drugs, depending on
how long the remission lasted. A stem cell transplant may be considered for children
whose leukemia comes back during treatment or within 6 months after treatment,
especially if there is a brother or sister who is a good match. Stem cell transplant may
also be used for other children who relapse after a second course of chemo.

Some children have a relapse in which leukemia cells are found in one part of the body
(such as the cerebrospinal fluid or the testicles) but are not found in the bone marrow.
These children may have radiation treatment, along with intense chemo, to the affected
area.

Treatment of children with acute myeloid leukemia

Treatment for most children with acute myeloid leukemia (AML) has 2 phases:

?

Induction

???? Consolidation (intensification)
Because treatment is very intense and there is a risk of serious complications, children
with AML should be treated in cancer centers or hospitals that have a lot of experience
with this disease.

Induction

The combinations of drugs used to treat AML are different from those used for ALL.
Treatment is given in cycles that usually last several days. The schedule of treatment may
be repeated in 10 days or 2 weeks, depending on how intense the doctor wants the
treatment to be. Treatment is repeated until the bone marrow shows no more leukemia.
This usually happens after 2 or 3 treatments. Often chemo is put into the cerebrospinal
fluid (CSF), too. Usually radiation treatment to the brain is not needed.

Consolidation (intensification)

This phase begins after a remission when no more leukemia cells are seen in the bone
marrow. About 1 out of 5 children has a brother or sister who would be a good stem cell
donor. For these children, a stem cell transplant is often recommended. Most studies have
found this improves the chance for long-term survival over chemo alone. But it is also
more likely to cause serious complications. For children with good prognostic factors,
some doctors may recommend just giving high-dose chemo and holding off on the stem
cell transplant in case the AML relapses.

For most children, high-dose chemo is given for at least several months. Chemo into the
CSF is usually given at the start and every 1 to 2 months for as long as this phase lasts.

Most children with AML (except those with acute promyelocytic leukemia) do not need
maintenance chemo.

An important aspect of treatment for AML is supportive care (nursing care, nutrition,
antibiotic use, blood transfusions, etc.). With this care, a high rate of remission at the end
of induction can be achieved.

Treatment of refractory or recurrent AML

Less than 15% of children have refractory AML (leukemia that does not respond to initial
treatment). These leukemias are often very hard to cure. The doctor may recommend
some type of stem cell transplant if it can be done.

As a rule, the outlook for a child whose AML comes back after treatment is slightly
better than if a remission were never achieved. But this depends on how long the first

remission lasted. More than half of these children will go into a second remission with
more chemo. The chance of a second remission is better if the first one lasted for at least
a year, but long-term second remissions are rare without a stem cell transplant.

Most children whose leukemia has relapsed will be offered a clinical trial in the hope that
if a remission is brought about, a stem cell transplant can be done. Sometimes the doctor
may suggest a stem cell transplant even without a remission.

Treatment of children with acute promyelocytic leukemia

Treatment of acute promyelocytic leukemia (APL) differs from usual AML treatment.
Most children respond well to this treatment.

Induction

Along with chemo, children with APL get a drug something like vitamin A called ATRA
(all-trans retinoic acid). Although ATRA alone often brings about a remission, combining
it with chemo gives better long-term results.

Spread to the brain or spinal cord is very rare with APL, so these areas most often do not
need to be treated with chemo.

The side effects of ATRA treatment differ from those of standard AML chemo because
of a possible problem called retinoic acid syndrome. It can lead to breathing problems
due to fluid build-up in the lungs, low blood pressure, kidney damage, and severe fluid
build-up elsewhere in the body. It can often be treated by stopping the ATRA for a while
and giving a steroid.

During treatment, some patients with APL may also have blood-clotting problems. They
may be given a "blood thinner" to help prevent or treat this.

Consolidation (Intensification)

This is usually much like induction, involving both ATRA and chemo. Because of the
success of this treatment, stem cell transplant is not usually advised as long as the child
stays in remission.

Maintenance

Children with APL may get maintenance therapy with ATRA, often with chemo, for
about one year.

Relapsed APL

If the leukemia comes back after treatment, most patients can be put into a second
remission. Arsenic trioxide is a drug that works very well in this setting, but it can
sometimes cause problems with heart rhythms. Children getting this drug need to have

their blood mineral levels watched closely. A stem cell transplant may be considered
once a second remission is brought about.

Treatment of children with juvenile myelomonocytic leukemia

Juvenile myelomonocytic leukemia (JMML) is fairly rare, and there is no standard
treatment for this leukemia. A stem cell transplant offers the best chance to cure JMML
and is the treatment of choice when possible. About 50% of children with JMML who get
a stem cell transplant are still free of leukemia after several years. Because it is hard to
treat with current chemo drugs, taking part in a clinical trial looking at newer drugs may
be a good option for children who cannot get a stem cell transplant.

Treatment of children with chronic myelogenous leukemia

Chronic myelogenous leukemia (CML) is rare in children, but it does occur. Treatment in
children is like treatment in adults. High-dose chemo with a stem cell transplant offers
the best chance for a cure, and is most often the treatment of choice if it is available.

Some targeted drugs attack cells with the Philadelphia chromosome, which is present in
some patients with CML. These drugs are usually work well at keeping CML under
control, often for a long time and with less severe side effects than with chemo drugs. But
these drugs do not cure CML when used by themselves, and they must be taken every
day. Doctors are now looking at whether adding these drugs to stem cell transplant plans
can help increase cure rates.

To learn more about CML and its treatment, see our document, Leukemia--Chronic
Myeloid.

Status of acute leukemia after treatment

How well a leukemia responds to the first (induction) treatment has an effect on long-
term outlook.

A remission or complete remission is usually defined as showing no disease after the 4-6
weeks of induction treatment. This means the bone marrow has fewer than 5% blast cells,
the blood cell counts are within normal limits, and there are no signs or symptoms of the
disease. A molecular complete remission means there is no evidence of leukemia cells in
the bone marrow, even when using very sensitive lab tests.

Minimal residual disease is a term used after treatment when leukemia cells can't be
found in the bone marrow using standard lab tests (such as looking at cells under a
microscope), but more sensitive tests find that leukemia cells are still in the bone marrow.

Active disease means that either the leukemia is still present during treatment or that the
disease has relapsed (come back) after treatment. For a patient to be in relapse, more than
5% of the marrow must be made up of blast cells.

Clinical trials

You may have had to make a lot of decisions since you've been told that your child has
cancer. One of the most important decisions you will make is deciding which treatment is
best for your child. You may have heard about clinical trials being done for his or her
type of cancer. Or maybe someone on your health care team has mentioned a clinical trial
to you.

Clinical trials are carefully controlled research studies that are done with patients who
volunteer for them. They are done to get a closer look at promising new treatments or
procedures.

If you would like your child to take part in a clinical trial, you should start by asking your
doctor if your clinic or hospital conducts clinical trials. You can also call our clinical
trials matching service for a list of clinical trials that meet your medical needs. You can
reach this service at 1-800-303-5691 or on our Web site at www.cancer.org/clinicaltrials.
You can also get a list of current clinical trials by calling the National Cancer Institute's
Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) or by
visiting the NCI clinical trials Web site at www.cancer.gov/clinicaltrials.

There are requirements your child must meet to take part in any clinical trial. If he or she
does qualify for a clinical trial, it is up to you whether or not to enter (enroll in) it.

Clinical trials are one way to get state-of-the art cancer treatment. They are the only way
for doctors to learn better methods to treat cancer. Still, they are not right for everyone.

You can get a lot more information on clinical trials in our document called Clinical
Trials: What You Need to Know. You can read it on our Web site or call our toll-free
number and have it sent to you.

Complementary and alternative therapies

When your child has cancer you are likely to hear about ways to treat his or her cancer or
relieve symptoms that your doctor hasn't mentioned. Everyone from friends and family to
Internet groups and Web sites offer ideas for what might help. These methods can include
vitamins, herbs, and special diets, or other methods such as acupuncture or massage, to
name a few.

What are complementary and alternative therapies?

It can be confusing because not everyone uses these terms the same way, and they are
used to refer to many different methods. We use complementary to refer to treatments
that are used along with your regular medical care. Alternative treatments are used
instead of a doctor's medical treatment.

Complementary methods: Most complementary treatment methods are not offered as
cures for cancer. Mainly, they are used to help the person with cancer feel better. Some
examples of methods that are used along with regular treatment are: art therapy or play
therapy to reduce stress, acupuncture to help relieve pain, or peppermint tea to relieve

Targeted therapy

In recent years, new drugs that are aimed at certain parts of cancer cells have been
developed. These are called targeted drugs. They work differently than standard chemo
drugs. They often have less severe side effects. Some of these drugs may be useful in
certain cases of childhood leukemia.

These drugs are taken daily as pills. Possible side effects include diarrhea, nausea, muscle
pain, fatigue, and skin rashes. Often these side effects are mild. A common side effect is
swelling around the eyes or in the hands or feet.

High-dose chemotherapy and stem cell transplant

Stem cell transplant (SCT) can sometimes be used for children whose chances of survival
are poor with standard or even intense chemo. SCT allows doctors to use very high doses
of chemo. The high doses of these drugs destroy the bone marrow, which keeps new
blood cells from being made. This poses a threat to the child's life. But after treatment is
finished, the child gets a transplant of blood-forming stem cells to replace the bone
marrow. Stem cells are very early cells that are able to make new blood cells.

Types of transplants

There are 2 main types of stem cell transplants: allogeneic and autologous. The
difference is the source of the blood-forming stem cells.

Allogeneic SCT: For childhood leukemia, the blood-forming stem cells most often come
from another person. This is called an allogeneic stem cell transplant.

Usually the donor is a brother or sister but, rarely, the donor could be an unrelated
volunteer. Stored cells from umbilical cord blood have also been used for unrelated donor
transplants. These stem cells come from blood drained from the umbilical cord and
placenta after a baby is born and the cord is cut.

Autologous SCT: In an autologous stem cell transplant, the patient's own stem cells are
removed from his or her bone marrow or bloodstream. They are frozen until after
treatment with chemo and/or radiation and then given back to the patient.

This procedure is rarely used for childhood leukemia, for a couple of reasons. One
concern is that there may be leukemia cells among the stem cells, which could be given
back to the child after treatment. To avoid this, the doctors treat the stored cells with
drugs to try to kill any cancer cells. And leukemia has more of a chance to relapse when
the child's own stem cells are used. So stem cells from a donor are more often used.

When SCT may be used

SCT may be used for children with ALL whose leukemia comes back early after going
into remission. It is less clear whether it should be used if more than 6 months has passed

since the chemo was given. These children will often do well with another round of
standard chemo.

Because AML comes back more often, some doctors recommend SCT for some children
with AML right after they have gone into remission, especially if the child has a brother
or sister who can donate cells. If the cancer comes back after the first round of chemo,
then most doctors will suggest SCT as soon as the child goes into remission again.

In any case, it is important that the patient be in remission before the transplant.
Otherwise, the leukemia is more likely to return.

What SCT involves

Here is how the SCT process works: Stem cells are collected from either the bone
marrow or from the bloodstream. The cells are frozen and stored. The child is then given
very high doses of chemo (and sometimes radiation) to kill the cancer cells. All of the
normal cells in the bone marrow are also killed. After treatment, the stored stem cells are
thawed and given to the child as a blood transfusion. Then the waiting begins as the stem
cells settle in the child's bone marrow and start to grow and make new blood cells. For
the next 3 to 4 weeks the patient is a high risk for serious infections (because of low
white blood cell counts), as well as bleeding (because of low platelet counts).
Transfusions and antibiotics are often used to prevent or treat these problems.

Patients most often stay in the hospital until a certain white blood cell count (called the
ANC) is near 1,000. The child is then seen in an outpatient clinic almost every day for
several weeks.

Stem cell transplant is a complex treatment. If the doctors think that a child with
leukemia might be helped by this treatment, it is important that it be done at a hospital
where the staff has a lot or experience with the procedure.

Stem cell transplant can also be very expensive (costing more than $100,000) and often
involves a long hospital stay. Because it is so costly, parents should be sure to get a
written approval from their insurer if their child is to have this treatment.

Side effects of SCT

Side effects from a stem cell transplant can be divided into early and long-term effects.
Early side effects are about the same as those of any other type of high-dose chemo: low
blood cell counts, nausea, vomiting, hair loss, etc. These side effects are caused by
damage to the bone marrow and other tissues that divide quickly. One of the most
common and serious short-term effects is the increased risk of severe infection.
Antibiotics are often given to try to prevent this. Other side effects, like low red blood
cell and platelet counts, may mean that the patient will need transfusions or other
treatments.

Long-term side effects: Some side effects can go on for a long time. Sometimes they
don't show up until months or even years after the transplant. Long-term side effects
could include the following:

? Graft-versus-host disease (see below)

? Radiation damage to the lungs

? Problems with the thyroid or other hormone-making glands

? Problems with fertility

??? Problems with bone growth
Graft-versus-host disease (GVHD) is a major concern of an allogeneic (donor) stem cell
transplant. It happens when the immune system of the patient is taken over by that of the
donor. The donor immune system then begins to attack the patient's other tissues and
organs.

Symptoms can include severe skin rashes with itching and severe diarrhea. The liver and
lungs may also be damaged. The patient may also become tired and have aching muscles.
If severe enough, the disease can be fatal. Drugs that weaken the immune system are
often given to try to keep GVHD under control.

To learn more about stem cell transplants, see our article Bone Marrow and Peripheral
Blood Stem Cell Transplant. You can find out more about long-term effects in the
section, "Moving on after treatment."

Treatment of children with acute lymphocytic leukemia

The main treatment for children with acute lymphocytic leukemia (ALL) is chemo, which
has 3 phases:

?

?

Induction

Consolidation (also called intensification)

? Maintenance

Induction

The goal of induction is to bring about a remission. This means that leukemia cells are no
longer found in bone marrow samples, the normal marrow cells return, and the blood
counts become normal. (A remission is not the same as a cure.) Children with ALL are
divided into risk groups to make sure that the correct types and doses of drugs are given.
More than 95% of children with ALL will go into remission after 1 month of treatment.

During induction, frequent trips to the doctor will be needed. Your child may spend some
or much of this time in the hospital. Children with standard-risk ALL often receive 3
drugs for the first month of treatment. A fourth drug is typically added for high-risk

children. All children will need to have spinal taps to put chemo right into the
cerebrospinal fluid (CSF) to try to keep cancer from spreading to the central nervous
system (brain and spinal cord). And some, such as those with T-cell leukemia, high white
blood cell counts, or cancer cells in the CSF, may need radiation to the head, too. This
was more common in the past, but recent studies have found that many children even
with high-risk ALL may not need radiation therapy if they are given more intense chemo.
Doctors try to avoid radiation because, no matter how low the dose, it may cause some
problems in thinking and growth.

Consolidation

The goal of this phase (also called intensification) is to get rid of leukemia cells from
places where they can "hide." This phase lasts about 4 to 8 weeks. Several drugs are used,
depending on the child's risk category. Some children may benefit from a stem cell
transplant at this time.

Maintenance

If the leukemia stays in remission after the first 2 phases of treatment, this last phase,
maintenance chemo, can begin. The total length of therapy for all 3 phases is 2 to 3 years
for most children with ALL. Because boys are at higher risk for relapse than girls, many
doctors favor giving them several more months of treatment.

Treatment of residual disease

All these treatment plans may change if the leukemia hasn't completely disappeared.
Soon after treatment has begun the doctor may check the child's bone marrow to see if
the leukemia is going away. If not, treatment may be increased or given for a longer time.
When the leukemia seems to have disappeared, the doctor may do a special chemical test
to look for leukemia cells. If any are found, then once again, chemo may be increased or
prolonged.

Treatment of recurrent ALL

If a child with ALL relapses (the leukemia comes back after treatment), he or she will
again be treated with chemo. This may include the same or different drugs, depending on
how long the remission lasted. A stem cell transplant may be considered for children
whose leukemia comes back during treatment or within 6 months after treatment,
especially if there is a brother or sister who is a good match. Stem cell transplant may
also be used for other children who relapse after a second course of chemo.

Some children have a relapse in which leukemia cells are found in one part of the body
(such as the cerebrospinal fluid or the testicles) but are not found in the bone marrow.
These children may have radiation treatment, along with intense chemo, to the affected
area.

Treatment of children with acute myeloid leukemia

Treatment for most children with acute myeloid leukemia (AML) has 2 phases:

?

Induction

???? Consolidation (intensification)
Because treatment is very intense and there is a risk of serious complications, children
with AML should be treated in cancer centers or hospitals that have a lot of experience
with this disease.

Induction

The combinations of drugs used to treat AML are different from those used for ALL.
Treatment is given in cycles that usually last several days. The schedule of treatment may
be repeated in 10 days or 2 weeks, depending on how intense the doctor wants the
treatment to be. Treatment is repeated until the bone marrow shows no more leukemia.
This usually happens after 2 or 3 treatments. Often chemo is put into the cerebrospinal
fluid (CSF), too. Usually radiation treatment to the brain is not needed.

Consolidation (intensification)

This phase begins after a remission when no more leukemia cells are seen in the bone
marrow. About 1 out of 5 children has a brother or sister who would be a good stem cell
donor. For these children, a stem cell transplant is often recommended. Most studies have
found this improves the chance for long-term survival over chemo alone. But it is also
more likely to cause serious complications. For children with good prognostic factors,
some doctors may recommend just giving high-dose chemo and holding off on the stem
cell transplant in case the AML relapses.

For most children, high-dose chemo is given for at least several months. Chemo into the
CSF is usually given at the start and every 1 to 2 months for as long as this phase lasts.

Most children with AML (except those with acute promyelocytic leukemia) do not need
maintenance chemo.

An important aspect of treatment for AML is supportive care (nursing care, nutrition,
antibiotic use, blood transfusions, etc.). With this care, a high rate of remission at the end
of induction can be achieved.

Treatment of refractory or recurrent AML

Less than 15% of children have refractory AML (leukemia that does not respond to initial
treatment). These leukemias are often very hard to cure. The doctor may recommend
some type of stem cell transplant if it can be done.

As a rule, the outlook for a child whose AML comes back after treatment is slightly
better than if a remission were never achieved. But this depends on how long the first

remission lasted. More than half of these children will go into a second remission with
more chemo. The chance of a second remission is better if the first one lasted for at least
a year, but long-term second remissions are rare without a stem cell transplant.

Most children whose leukemia has relapsed will be offered a clinical trial in the hope that
if a remission is brought about, a stem cell transplant can be done. Sometimes the doctor
may suggest a stem cell transplant even without a remission.

Treatment of children with acute promyelocytic leukemia

Treatment of acute promyelocytic leukemia (APL) differs from usual AML treatment.
Most children respond well to this treatment.

Induction

Along with chemo, children with APL get a drug something like vitamin A called ATRA
(all-trans retinoic acid). Although ATRA alone often brings about a remission, combining
it with chemo gives better long-term results.

Spread to the brain or spinal cord is very rare with APL, so these areas most often do not
need to be treated with chemo.

The side effects of ATRA treatment differ from those of standard AML chemo because
of a possible problem called retinoic acid syndrome. It can lead to breathing problems
due to fluid build-up in the lungs, low blood pressure, kidney damage, and severe fluid
build-up elsewhere in the body. It can often be treated by stopping the ATRA for a while
and giving a steroid.

During treatment, some patients with APL may also have blood-clotting problems. They
may be given a "blood thinner" to help prevent or treat this.

Consolidation (Intensification)

This is usually much like induction, involving both ATRA and chemo. Because of the
success of this treatment, stem cell transplant is not usually advised as long as the child
stays in remission.

Maintenance

Children with APL may get maintenance therapy with ATRA, often with chemo, for
about one year.

Relapsed APL

If the leukemia comes back after treatment, most patients can be put into a second
remission. Arsenic trioxide is a drug that works very well in this setting, but it can
sometimes cause problems with heart rhythms. Children getting this drug need to have

their blood mineral levels watched closely. A stem cell transplant may be considered
once a second remission is brought about.

Treatment of children with juvenile myelomonocytic leukemia

Juvenile myelomonocytic leukemia (JMML) is fairly rare, and there is no standard
treatment for this leukemia. A stem cell transplant offers the best chance to cure JMML
and is the treatment of choice when possible. About 50% of children with JMML who get
a stem cell transplant are still free of leukemia after several years. Because it is hard to
treat with current chemo drugs, taking part in a clinical trial looking at newer drugs may
be a good option for children who cannot get a stem cell transplant.

Treatment of children with chronic myelogenous leukemia

Chronic myelogenous leukemia (CML) is rare in children, but it does occur. Treatment in
children is like treatment in adults. High-dose chemo with a stem cell transplant offers
the best chance for a cure, and is most often the treatment of choice if it is available.

Some targeted drugs attack cells with the Philadelphia chromosome, which is present in
some patients with CML. These drugs are usually work well at keeping CML under
control, often for a long time and with less severe side effects than with chemo drugs. But
these drugs do not cure CML when used by themselves, and they must be taken every
day. Doctors are now looking at whether adding these drugs to stem cell transplant plans
can help increase cure rates.

To learn more about CML and its treatment, see our document, Leukemia--Chronic
Myeloid.

Status of acute leukemia after treatment

How well a leukemia responds to the first (induction) treatment has an effect on long-
term outlook.

A remission or complete remission is usually defined as showing no disease after the 4-6
weeks of induction treatment. This means the bone marrow has fewer than 5% blast cells,
the blood cell counts are within normal limits, and there are no signs or symptoms of the
disease. A molecular complete remission means there is no evidence of leukemia cells in
the bone marrow, even when using very sensitive lab tests.

Minimal residual disease is a term used after treatment when leukemia cells can't be
found in the bone marrow using standard lab tests (such as looking at cells under a
microscope), but more sensitive tests find that leukemia cells are still in the bone marrow.

Active disease means that either the leukemia is still present during treatment or that the
disease has relapsed (come back) after treatment. For a patient to be in relapse, more than
5% of the marrow must be made up of blast cells.

Clinical trials

You may have had to make a lot of decisions since you've been told that your child has
cancer. One of the most important decisions you will make is deciding which treatment is
best for your child. You may have heard about clinical trials being done for his or her
type of cancer. Or maybe someone on your health care team has mentioned a clinical trial
to you.

Clinical trials are carefully controlled research studies that are done with patients who
volunteer for them. They are done to get a closer look at promising new treatments or
procedures.

If you would like your child to take part in a clinical trial, you should start by asking your
doctor if your clinic or hospital conducts clinical trials. You can also call our clinical
trials matching service for a list of clinical trials that meet your medical needs. You can
reach this service at 1-800-303-5691 or on our Web site at www.cancer.org/clinicaltrials.
You can also get a list of current clinical trials by calling the National Cancer Institute's
Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) or by
visiting the NCI clinical trials Web site at www.cancer.gov/clinicaltrials.

There are requirements your child must meet to take part in any clinical trial. If he or she
does qualify for a clinical trial, it is up to you whether or not to enter (enroll in) it.

Clinical trials are one way to get state-of-the art cancer treatment. They are the only way
for doctors to learn better methods to treat cancer. Still, they are not right for everyone.

You can get a lot more information on clinical trials in our document called Clinical
Trials: What You Need to Know. You can read it on our Web site or call our toll-free
number and have it sent to you.

Complementary and alternative therapies

When your child has cancer you are likely to hear about ways to treat his or her cancer or
relieve symptoms that your doctor hasn't mentioned. Everyone from friends and family to
Internet groups and Web sites offer ideas for what might help. These methods can include
vitamins, herbs, and special diets, or other methods such as acupuncture or massage, to
name a few.

What are complementary and alternative therapies?

It can be confusing because not everyone uses these terms the same way, and they are
used to refer to many different methods. We use complementary to refer to treatments
that are used along with your regular medical care. Alternative treatments are used
instead of a doctor's medical treatment.

Complementary methods: Most complementary treatment methods are not offered as
cures for cancer. Mainly, they are used to help the person with cancer feel better. Some
examples of methods that are used along with regular treatment are: art therapy or play
therapy to reduce stress, acupuncture to help relieve pain, or peppermint tea to relieve

nausea. Some complementary methods are known to help, while others have not been
tested. Some have been proven not be helpful, and a few are even harmful.

Alternative treatments: Alternative treatments may be offered as cancer cures. These
treatments have not been proven safe and effective in clinical trials. Some of these
methods may be harmful, or have life-threatening side effects. But the biggest danger in
most cases is that you may lose the chance to be helped by standard medical treatment.
Delays or interruptions in your medical treatments may give the cancer more time to
grow and make it less likely that treatment will help.

Finding out more

It is easy to see why parents who have children with cancer think about alternative
methods. You want to do all you can to help fight the cancer, and the idea of a treatment
with no side effects sounds great. Sometimes medical treatments like chemotherapy can
be hard to take, or they may no longer be working. But the truth is that most of these
alternative methods have not been tested and proven to work in treating cancer.

As you think about your child's options, here are 3 important steps you can take:

Look for "red flags" that suggest fraud. Does the method promise to cure all or
most cancers? Are you told not to use regular medical treatments? Is the treatment
a "secret" that requires you to take your child to certain providers or to another
country?

Talk to your child's doctor or nurse about any method you are thinking of using.

Contact us at 1-800-227-2345 to learn more about complementary and alternative
methods in general and to find out about the specific methods you are looking at.

The choice is yours

You always have a say in how your child's cancer is treated. If you want to consider a
non-standard treatment, learn all you can about the method and talk to your child's doctor
about it. With good information and the support of your child's health care team, you may
be able to safely use the methods that can help your child while avoiding those that could
be harmful.

What are some questions you can ask the
doctor?

As you cope with your child's cancer and cancer treatment, we encourage you to have
honest, open talks with the doctor. Feel free to ask any question that's on your mind, no
matter how small it might seem. Here are some questions you might want to ask. Be sure
to add your own questions as you think of them. Nurses, social workers, and other
members of the treatment team may also be able to answer many of your questions.

Would you write down exactly what kind of leukemia my child has?

Are there any factors that might affect my child's outlook?

Are there other tests that need to be done before we can decide on treatment?

How much experience do you have treating this type of leukemia?

Should we get a second opinion?

What treatment choices do we have?

What do you recommend and why?

Should we think about a stem cell transplant?

What risks or side effects are there to the treatments you recommend?

Which side effects start shortly after treatment and which ones may happen later
on?

What are the chances of the leukemia coming back with these treatment plans?
What would we do if this happens?

What should we do to be ready for treatment?

How long will treatment last? What will it involve? Where will it be done?

How will treatment affect our daily activities?

What type of follow-up will we need after treatment?

How will we pay for treatment? Will our insurance cover all or part of it?
Add your own questions below:

Moving on after treatment

It can feel good to be done with treatment, but it can also be stressful. You may find that
you now worry about the cancer coming back. This is a very common concern among
those who have dealt with cancer. (When cancer comes back, it is called a recurrence.)

It may take a while before your child's recovery begins to feel real and your fears are
somewhat relieved. You can learn more about what to look for and how to learn to live
with the chance of cancer coming back in Living With Uncertainty: The Fear of Cancer
Recurrence.

Follow-up exams

Follow-up exams are needed for several years after treatment. These visits are very
important. The doctor will watch for signs that the cancer has come back, as well as for
short-term and long-term side effects of treatment. Be sure to report any new symptoms
to the doctor right away so that relapse or side effects can be watched and treated, if
needed.

Check-ups for children with leukemia involve careful physical exams, lab tests, and,
sometimes, x-rays. These check-ups will usually happen monthly during the first year,
and then less often for at least 5 years after treatment. After that time, most children see
their doctor at least every year for a check-up.

If the leukemia returns, it usually does so during treatment or within a year or so after
treatment ends. It's unusual for ALL or AML to come back if there are no signs of the
disease within the next 2 years.

It is also important to keep health insurance. Even though no one wants to think of the
cancer coming back, it could happen. If so, the last thing you want is to have to worry
about paying for treatment.

Long-term effects of cancer treatment

Because of major advances in treatment, more children treated for cancer are living into
adulthood. With childhood cancer survivors living longer, their health as they get older
has come more into focus in recent years.

Just as the treatment of childhood cancer requires a very special approach, so does
follow-up and watching for late effects. Careful follow-up after cancer treatment is very
important.

Childhood cancer survivors are at risk, to some degree, for several possible late effects of
their cancer treatment. This risk depends on a number of factors, such as the type of
cancer, the cancer treatments given, dosages of cancer treatment, and age at time of
treatment.

One of the most serious side effects of ALL treatment is the chance of getting acute
myelogenous leukemia (AML) at a later time. This happens in about 5% of treated
patients after they have had certain types of chemo drugs. Less often, children cured of
leukemia may later develop non-Hodgkin lymphomas or other cancers. Of course, the
risk of getting these second cancers must be balanced against the clear value of treating a
life-threatening disease like leukemia with chemo.

Children whose treatment for leukemia has included radiation therapy of the brain may
have some decrease in their learning ability. In most cases, this is very mild and does not
cause any major disability. Still, doctors try to limit radiation to the brain whenever they
can.

Survivors of childhood leukemia often suffer from psychological problems. They also
may have some problems with normal functioning and school work. These often can be
helped with support and encouragement. Another problem is that the treatments may
reduce growth in children and they may end up a bit shorter as adults. This is especially
true after stem cell transplants. This can be helped by the treating survivors with growth
hormone, if needed.

Thinning of the bones (osteoporosis), with a chance of bone fracture, may result from the
use of some steroid drugs.

Other late effects may include the following:

Heart or lung problems after getting certain chemo drugs or radiation treatment

Changes in sexual development and the ability to have children
There may be other possible problems from treatment that your child's doctor should
carefully review with you before starting treatment. Special centers are often the best
places for children to be treated when such effects happen.

To help improve follow-up care of childhood cancer survivors throughout their lives, the
Children's Oncology Group (COG) has written long-term follow-up guidelines for
doctors. These guidelines describe in detail the suggested long-term follow-up care based
on the treatments the child has received. To learn more, ask your child's doctors about the
COG survivor guidelines. And for more information about late effects, please see our
document, Childhood Cancer: Late Effects of Cancer Treatment.

Moving on

After treatment is finished, you and your child may want to put the experience behind
you as much as you can. Some day your child will be on his or her own and have new
doctors. It is important that you or your child be able to give the new doctors the exact
details of the cancer diagnosis and treatment. Gathering the details soon after treatment
may be easier than trying to get them at some point in the future. There are certain pieces
of information you should keep copies of and see that your child's doctors have, even into
adulthood. These include:

A copy of the pathology report from any biopsies or surgeries.

If surgery was done, a copy of the operative report.

If there were hospitalizations, a copy of the discharge summaries that doctors
prepare when patients leave the hospital.

A list of the final doses of each drug your child had. (Certain chemo drugs have
specific long-term side effects. If you can get a list of these from the pediatric
oncologist, this would also help any new doctor.)

If radiation was given, a final summary of the dose and field.
What's new in childhood leukemia research?

Research into all aspects of childhood leukemia is now being done at many medical
centers and hospitals.

Genetics

Scientists are making great progress in understanding how changes in DNA (the
substance that holds information on cell growth and function) can cause normal cells to
change into leukemia cells. Today, there are much better tests for finding the disease and
for telling exactly what kind of leukemia a child has and how well treatment is working.
For example, one test (called PCR) can find one tumor cell among a million normal cells.

Clinical trials

Clinical trials are taking place to study why some children relapse, which children need
more intense treatment, which drugs work the best, and whether natural substances made
by the body can help the immune system fight the leukemia cells. These and many other
issues are being addressed in clinical trials. Answers to these questions will mean better
treatment of childhood leukemia in the future.