This cancer treatment information summary provides an overview of the prognosis, diagnosis, classification, and treatment of childhood acute lymphoblastic leukemia (ALL).

The National Cancer Institute provides the PDQ pediatric cancer treatment information summaries as a public service to increase the availability of evidence-based cancer information to health professionals, patients, and the public. These summaries are updated regularly according to the latest published research findings by an Editorial Board of pediatric oncology specialists.

Cancer in children and adolescents is rare. Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the primary care physician, pediatric surgical subspecialists, radiation oncologists, pediatric medical oncologists/hematologists, rehabilitation specialists, pediatric nurse specialists, social workers, and others in order to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life. Refer to the PDQ Supportive Care summaries for specific information about supportive care for children and adolescents with cancer.

Guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer have been outlined by the American Academy of Pediatrics.[1] Since treatment of children with ALL entails many potential complications and requires intensive supportive care (transfusions; management of infectious complications; and emotional, financial, and developmental support), this treatment is best coordinated by pediatric oncologists and performed in cancer centers or hospitals with all of the necessary pediatric supportive care facilities. Specialized care is essential for all children with ALL, including those in whom specific clinical and laboratory features might confer a favorable prognosis. At the same time, it is equally important that the clinical centers and the specialists directing the patient’s care maintain contact with the referring physician in the community. Strong lines of communication optimize any urgent or interim care required when the child is at home.

In recent decades, dramatic improvements in survival have been achieved for children and adolescents with cancer. Childhood and adolescent cancer survivors require close follow-up because cancer therapy side effects may persist or develop months or years after treatment. Refer to the PDQ Late Effects of Childhood Cancer Therapies summary for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.

ALL is the most common cancer occurring in children, representing 23% of cancer diagnoses among children younger than 15 years and occurring at an annual rate of approximately 30 to 40 per million.[2] There are approximately 2,400 children and adolescents younger than 20 years diagnosed with ALL each year in the United States,[3] and there has been a gradual increase in the incidence of ALL in the past 25 years.[4] There is a sharp peak in ALL incidence among children ages 2 to 3 years (>80 per million per year), with rates decreasing to 20 per million for ages 8 to 10 years. The incidence of ALL among children ages 2 to 3 years is approximately 4-fold greater than that for infants and is nearly 10-fold greater than that for children who are 19 years old. For unexplained reasons, the incidence of ALL is substantially higher for white children than for black children, with a nearly 3-fold higher incidence at 2 to 3 years for white children compared to black children.[3] The incidence of ALL appears to be highest in Hispanic children (43 per million).[5]

There are few identified factors associated with increased risk of ALL.[3] The primary accepted nongenetic risk factors for ALL are prenatal exposure to x-rays and postnatal exposure to high doses of radiation (e.g., therapeutic radiation as previously used for conditions such as tinea capitis and thymus enlargement).[6] Children with Down syndrome have increased risk for developing both ALL and acute myeloid leukemia (AML),[7] with a cumulative risk for developing leukemia of approximately 2.1% by age 5 years and 2.7% by age 30 years.[8] Approximately two thirds of the cases of acute leukemia in children with Down syndrome are ALL.[8] Increased occurrence of ALL is also associated with certain genetic conditions, including neurofibromatosis,[9] Shwachman syndrome,[10,11] Bloom syndrome,[12] and ataxia telangiectasia.[13]

Certain cases of ALL that develop in children may have a prenatal origin. Evidence in support of this comes from the observation that the immunoglobulin or T-cell receptor antigen rearrangements that are unique to each patient’s leukemia cells can be detected in blood samples obtained at birth.[14,15] Similarly, there are data that patients with ALL characterized by specific chromosomal translocations have blood cells carrying the translocation at the time of birth.[14-18]

Seventy-five percent to 80% of children with ALL attain remission and survive free of leukemia recurrence at least 5 years from diagnosis with current treatments that incorporate systemic therapy (e.g., combination chemotherapy) and specific central nervous system (CNS) preventive therapy (i.e., intrathecal chemotherapy with or without cranial irradiation).[2,3,19,20] Ten-year event-free survival of multiple large prospective trials conducted in different countries for children treated primarily in the 1980s is approximately 70%.[21-27]

Despite the treatment advances noted in childhood ALL, numerous important biologic and therapeutic questions remain to be answered in order to achieve the goal of curing every child with ALL. The systematic investigation of these issues requires large clinical trials, and the opportunity to participate in these trials is offered to most patients/families. Clinical trials for children and adolescents with ALL are generally designed to compare potentially better therapy with therapy that is currently accepted as standard. Much of the progress made in identifying curative therapies for childhood ALL and other childhood cancers has been achieved through investigator-driven discovery tested in carefully randomized, controlled clinical trials.[28,29] Information about ongoing clinical trials is available from the NCI Cancer.gov Web site.

References

1. Guidelines for the pediatric cancer center and role of such centers in diagnosis and treatment. American Academy of Pediatrics Section Statement Section on Hematology/Oncology. Pediatrics 99 (1): 139-41, 1997.  [PUBMED Abstract]
   
   
2. Ries LA, Kosary CL, Hankey BF, et al., eds.: SEER Cancer Statistics Review, 1973-1996. Bethesda, Md: National Cancer Institute, 1999. Also available online. Last accessed April 14, 2004. 
   
   
3. Smith MA, Ries LA, Gurney JG, et al.: Leukemia. In: Ries LA, Smith MA, Gurney JG, et al., eds.: Cancer incidence and survival among children and adolescents: United States SEER Program 1975-1995. Bethesda, Md: National Cancer Institute, SEER Program, 1999. NIH Pub.No. 99-4649. Also available online. Last accessed March 5, 2004, pp 17-34. Also available online. Last accessed April 14, 2004. 
   
   
4. Xie Y, Davies SM, Xiang Y, et al.: Trends in leukemia incidence and survival in the United States (1973-1998). Cancer 97 (9): 2229-35, 2003.  [PUBMED Abstract]
   
   
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6. Ross JA, Davies SM, Potter JD, et al.: Epidemiology of childhood leukemia, with a focus on infants. Epidemiol Rev 16 (2): 243-72, 1994.  [PUBMED Abstract]
   
   
7. Avet-Loiseau H, Mechinaud F, Harousseau JL: Clonal hematologic disorders in Down syndrome. A review. J Pediatr Hematol Oncol 17 (1): 19-24, 1995.  [PUBMED Abstract]
   
   
8. Hasle H, Clemmensen IH, Mikkelsen M: Risks of leukaemia and solid tumours in individuals with Down's syndrome. Lancet 355 (9199): 165-9, 2000.  [PUBMED Abstract]
   
   
9. Stiller CA, Chessells JM, Fitchett M: Neurofibromatosis and childhood leukaemia/lymphoma: a population-based UKCCSG study. Br J Cancer 70 (5): 969-72, 1994.  [PUBMED Abstract]
   
   
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11. Woods WG, Roloff JS, Lukens JN, et al.: The occurrence of leukemia in patients with the Shwachman syndrome. J Pediatr 99 (3): 425-8, 1981.  [PUBMED Abstract]
    
    
12. Passarge E: Bloom's syndrome: the German experience. Ann Genet 34 (3-4): 179-97, 1991.  [PUBMED Abstract]
    
    
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14. Yagi T, Hibi S, Tabata Y, et al.: Detection of clonotypic IGH and TCR rearrangements in the neonatal blood spots of infants and children with B-cell precursor acute lymphoblastic leukemia. Blood 96 (1): 264-8, 2000.  [PUBMED Abstract]
    
    
15. Taub JW, Konrad MA, Ge Y, et al.: High frequency of leukemic clones in newborn screening blood samples of children with B-precursor acute lymphoblastic leukemia. Blood 99 (8): 2992-6, 2002.  [PUBMED Abstract]
    
    
16. Ford AM, Bennett CA, Price CM, et al.: Fetal origins of the TEL-AML1 fusion gene in identical twins with leukemia. Proc Natl Acad Sci U S A 95 (8): 4584-8, 1998.  [PUBMED Abstract]
    
    
17. Wiemels JL, Cazzaniga G, Daniotti M, et al.: Prenatal origin of acute lymphoblastic leukaemia in children. Lancet 354 (9189): 1499-503, 1999.  [PUBMED Abstract]
    
    
18. Greaves MF, Maia AT, Wiemels JL, et al.: Leukemia in twins: lessons in natural history. Blood 102 (7): 2321-33, 2003.  [PUBMED Abstract]
    
    
19. Pui CH, Evans WE: Acute lymphoblastic leukemia. N Engl J Med 339 (9): 605-15, 1998.  [PUBMED Abstract]
    
    
20. Pui CH, Campana D, Evans WE: Childhood acute lymphoblastic leukaemia--current status and future perspectives. Lancet Oncol 2 (10): 597-607, 2001.  [PUBMED Abstract]
    
    
21. Gaynon PS, Trigg ME, Heerema NA, et al.: Children's Cancer Group trials in childhood acute lymphoblastic leukemia: 1983-1995. Leukemia 14 (12): 2223-33, 2000.  [PUBMED Abstract]
    
    
22. Schrappe M, Reiter A, Zimmermann M, et al.: Long-term results of four consecutive trials in childhood ALL performed by the ALL-BFM study group from 1981 to 1995. Berlin-Frankfurt-Münster. Leukemia 14 (12): 2205-22, 2000.  [PUBMED Abstract]
    
    
23. Harms DO, Janka-Schaub GE: Co-operative study group for childhood acute lymphoblastic leukemia (COALL): long-term follow-up of trials 82, 85, 89 and 92. Leukemia 14 (12): 2234-9, 2000.  [PUBMED Abstract]
    
    
24. Silverman LB, Declerck L, Gelber RD, et al.: Results of Dana-Farber Cancer Institute Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1981-1995). Leukemia 14 (12): 2247-56, 2000.  [PUBMED Abstract]
    
    
25. Maloney KW, Shuster JJ, Murphy S, et al.: Long-term results of treatment studies for childhood acute lymphoblastic leukemia: Pediatric Oncology Group studies from 1986-1994. Leukemia 14 (12): 2276-85, 2000.  [PUBMED Abstract]
    
    
26. Pui CH, Boyett JM, Rivera GK, et al.: Long-term results of Total Therapy studies 11, 12 and 13A for childhood acute lymphoblastic leukemia at St Jude Children's Research Hospital. Leukemia 14 (12): 2286-94, 2000.  [PUBMED Abstract]
    
    
27. Eden OB, Harrison G, Richards S, et al.: Long-term follow-up of the United Kingdom Medical Research Council protocols for childhood acute lymphoblastic leukaemia, 1980-1997. Medical Research Council Childhood Leukaemia Working Party. Leukemia 14 (12): 2307-20, 2000.  [PUBMED Abstract]
    
    
28. Progress against childhood cancer: the Pediatric Oncology Group experience. Pediatrics 89 (4 Pt 1): 597-600, 1992.  [PUBMED Abstract]
    
    
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