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.

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 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 acute lymphoblastic leukemia (ALL) entails many potential complications and requires intensive supportive care (e.g., 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 for whom specific clinical and laboratory features might confer a favorable prognosis. 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 in 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 Treatment for Childhood Cancer 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 diagnosed in children and represents 23% of cancer diagnoses among children younger than 15 years. ALL occurs 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.[4,5] A sharp peak in ALL incidence is observed among children aged 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 aged 2 to 3 years is approximately fourfold greater than that for infants and is nearly tenfold greater than that for adolescents who are 19 years old. For unexplained reasons, the incidence of ALL is substantially higher in white children than in black children, with a nearly threefold higher incidence from age 2 to 3 years in white children compared with black children.[3] The incidence of ALL appears to be highest in Hispanic children (43 per million).[6]

There are few identified factors associated with an 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).[7] Children with Down syndrome have increased risk of developing both ALL [8] and acute myeloid leukemia (AML),[9] with a cumulative risk of developing leukemia of approximately 2.1% by age 5 years and 2.7% by age 30 years.[10] Approximately one-half to two-thirds of the cases of acute leukemia in children with Down syndrome are ALL. Patients with ALL and Down syndrome have a lower incidence of both favorable and unfavorable cytogenetic findings and a lower incidence of T-cell phenotype.[8,10-13] While the vast majority of cases of AML in children with Down syndrome occur before the age of 4 years (median age, 1 year),[10,13] ALL in children with Down syndrome has an age distribution similar to that of ALL in non–Down syndrome children, with a median age of 3 to 4 years.[10,13] Outcome in Down syndrome children with ALL has generally been reported as poorer than that of non–Down syndrome children.[11,12,14] The lower event-free survival and overall survival in children with Down syndrome appear to be related to higher rates of treatment-related mortality, especially during induction therapy,[12,13] and to the absence of favorable biological features.[13,11] Increased occurrence of ALL is also associated with certain genetic conditions, including neurofibromatosis,[15] Shwachman syndrome,[16,17] Bloom syndrome,[18] and ataxia telangiectasia.[19]

Many cases of ALL that develop in children 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.[20,21] Similarly, there are data to support that patients with ALL characterized by specific chromosomal abnormalities had blood cells carrying the abnormalities at the time of birth.[20-22] Genetic studies of identical twins with concordant leukemia further support the prenatal origin of some leukemias.[23]

Among children with ALL, more than 95% attain remission and 75% to 85% 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 preventive therapy (i.e., intrathecal chemotherapy with or without cranial radiation).[2,3,24-32]

Despite the treatment advances noted in childhood ALL, numerous important biologic and therapeutic questions remain to be answered 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.[33,34] Information about ongoing clinical trials is available from the NCI 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 19, 2007. 
   
   
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., pp 17-34. Also available online. Last accessed April 19, 2007. 
   
   
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]
   
   
5. Shah A, Coleman MP: Increasing incidence of childhood leukaemia: a controversy re-examined. Br J Cancer 97 (7): 1009-12, 2007.  [PUBMED Abstract]
   
   
6. McNeil DE, Coté TR, Clegg L, et al.: SEER update of incidence and trends in pediatric malignancies: acute lymphoblastic leukemia. Med Pediatr Oncol 39 (6): 554-7; discussion 552-3, 2002.  [PUBMED Abstract]
   
   
7. 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]
   
   
8. Whitlock JA: Down syndrome and acute lymphoblastic leukaemia. Br J Haematol 135 (5): 595-602, 2006.  [PUBMED Abstract]
   
   
9. Hasle H: Pattern of malignant disorders in individuals with Down's syndrome. Lancet Oncol 2 (7): 429-36, 2001.  [PUBMED Abstract]
   
   
10. 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]
    
    
11. Bassal M, La MK, Whitlock JA, et al.: Lymphoblast biology and outcome among children with Down syndrome and ALL treated on CCG-1952. Pediatr Blood Cancer 44 (1): 21-8, 2005.  [PUBMED Abstract]
    
    
12. Chessells JM, Harrison G, Richards SM, et al.: Down's syndrome and acute lymphoblastic leukaemia: clinical features and response to treatment. Arch Dis Child 85 (4): 321-5, 2001.  [PUBMED Abstract]
    
    
13. Zeller B, Gustafsson G, Forestier E, et al.: Acute leukaemia in children with Down syndrome: a population-based Nordic study. Br J Haematol 128 (6): 797-804, 2005.  [PUBMED Abstract]
    
    
14. Whitlock JA, Sather HN, Gaynon P, et al.: Clinical characteristics and outcome of children with Down syndrome and acute lymphoblastic leukemia: a Children's Cancer Group study. Blood 106 (13): 4043-9, 2005.  [PUBMED Abstract]
    
    
15. 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]
    
    
16. Strevens MJ, Lilleyman JS, Williams RB: Shwachman's syndrome and acute lymphoblastic leukaemia. Br Med J 2 (6129): 18, 1978.  [PUBMED Abstract]
    
    
17. 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]
    
    
18. Passarge E: Bloom's syndrome: the German experience. Ann Genet 34 (3-4): 179-97, 1991.  [PUBMED Abstract]
    
    
19. Taylor AM, Metcalfe JA, Thick J, et al.: Leukemia and lymphoma in ataxia telangiectasia. Blood 87 (2): 423-38, 1996.  [PUBMED Abstract]
    
    
20. 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]
    
    
21. 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]
    
    
22. Greaves MF, Wiemels J: Origins of chromosome translocations in childhood leukaemia. Nat Rev Cancer 3 (9): 639-49, 2003.  [PUBMED Abstract]
    
    
23. Greaves MF, Maia AT, Wiemels JL, et al.: Leukemia in twins: lessons in natural history. Blood 102 (7): 2321-33, 2003.  [PUBMED Abstract]
    
    
24. Pui CH, Relling MV, Downing JR: Acute lymphoblastic leukemia. N Engl J Med 350 (15): 1535-48, 2004.  [PUBMED Abstract]
    
    
25. Pui CH, Evans WE: Treatment of acute lymphoblastic leukemia. N Engl J Med 354 (2): 166-78, 2006.  [PUBMED Abstract]
    
    
26. 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]
    
    
27. Schrappe M, Reiter A, Ludwig WD, et al.: Improved outcome in childhood acute lymphoblastic leukemia despite reduced use of anthracyclines and cranial radiotherapy: results of trial ALL-BFM 90. German-Austrian-Swiss ALL-BFM Study Group. Blood 95 (11): 3310-22, 2000.  [PUBMED Abstract]
    
    
28. 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]
    
    
29. 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]
    
    
30. Pui CH, Sandlund JT, Pei D, et al.: Improved outcome for children with acute lymphoblastic leukemia: results of Total Therapy Study XIIIB at St Jude Children's Research Hospital. Blood 104 (9): 2690-6, 2004.  [PUBMED Abstract]
    
    
31. Mitchell CD, Richards SM, Kinsey SE, et al.: Benefit of dexamethasone compared with prednisolone for childhood acute lymphoblastic leukaemia: results of the UK Medical Research Council ALL97 randomized trial. Br J Haematol 129 (6): 734-45, 2005.  [PUBMED Abstract]
    
    
32. Moghrabi A, Levy DE, Asselin B, et al.: Results of the Dana-Farber Cancer Institute ALL Consortium Protocol 95-01 for children with acute lymphoblastic leukemia. Blood 109 (3): 896-904, 2007.  [PUBMED Abstract]
    
    
33. Progress against childhood cancer: the Pediatric Oncology Group experience. Pediatrics 89 (4 Pt 1): 597-600, 1992.  [PUBMED Abstract]
    
    
34. Bleyer WA: The U.S. pediatric cancer clinical trials programmes: international implications and the way forward. Eur J Cancer 33 (9): 1439-47, 1997.  [PUBMED Abstract]
    
    

Back to Top

< Previous Section  |  Next Section >