This cancer treatment information summary provides an overview of the prognosis, diagnosis, classification, and treatment of childhood acute myeloid leukemia (AML) and other childhood myeloid malignancies.

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 children with cancer have been outlined by the American Academy of Pediatrics.[1] At these pediatric cancer centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate in these trials is offered to most patients/families. Clinical trials for children and adolescents with cancer are generally designed to compare potentially better therapy with therapy that is currently accepted as standard. Most of the progress made in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI Cancer.gov Web site.

AML is the most common type of myeloid malignancy of childhood. Between 75% and 85% of children with AML can achieve a complete remission following appropriate induction chemotherapy. Children with newly diagnosed AML have an event-free 5-year survival rate of approximately 50%.[2-4] The most consistent prognostic factor across studies of AML in children is white blood cell (WBC) count at diagnosis. Children who have a WBC count greater than 100,000/ml³ have a poor prognosis. In several studies, M4 and M5 French-American-British (FAB) subtype, WBC greater than 20,000/ml³, and requiring more than 1 cycle to achieve remission, predicted for a short duration of remission.[5,6] Cytogenetic and molecular characteristics are also associated with prognosis and are discussed in the Cytogenetic Evaluation and Molecular Abnormalities section of this summary.

Acute promyelocytic leukemia (APL) is a distinct subtype of AML and is treated differently than other types of AML. The characteristic chromosomal abnormality associated with APL is t(15;17). This translocation involves a breakpoint that includes the retinoid acid receptor and that leads to production of the PML-RARalpha fusion protein.[7] Clinically, APL is characterized by a severe coagulopathy often present at the time of diagnosis.[8] Mortality during induction due to bleeding complications is more common in this subtype than other FAB classifications.

Children with Down syndrome have an increased risk of leukemia with a ratio of ALL to AML typical for childhood acute leukemia, except during the first 3 years of life when AML (especially M7) predominates.[9] Neonates with Down syndrome may manifest a transient myeloproliferative syndrome (TMS). This disorder mimics congenital AML but improves spontaneously within 4 to 6 weeks. Retrospective surveys indicate that as many as 30% of infants with Down syndrome and TMS will develop AML before 3 years of age.[10] Interestingly, most children with Down syndrome and AML can be cured of their leukemia.[11] Appropriate therapy for these children is less intensive than current AML therapy and bone marrow transplant (BMT) is not indicated in first remission. Treatment outcome is very poor for patients with AML M7 in the absence of Down syndrome.[2,12,13]

The myelodysplastic syndromes (MDS) represent a heterogeneous group of disorders of hematopoiesis leading to variable degrees of pancytopenia and often AML. In adults, MDS have been classified by the FAB group into distinct categories.[14] The FAB MDS classification is not an adequate classification for the syndromes that occur in children. The World Health Organization (WHO) has developed a modified classification schema for MDS. Previously, MDS were classified as having less than 30% blasts. The WHO has changed the MDS classification to having less than 20% blasts.[15] The optimal management of MDS in children has not been well-studied in prospective trials.

Juvenile myelomonocytic leukemia (JMML), formerly termed juvenile chronic myeloid leukemia (JCML), is a rare hematopoietic malignancy of childhood accounting for less than 1% of all childhood leukemias.[16] A number of clinical and laboratory features distinguish JMML from adult-type chronic myeloid leukemia, a disease noted only occasionally in children. Few approaches other than hematopoietic stem cell transplantation have resulted in long-term survival for this disease.[17,18] Children with neurofibromatosis 1 (NF1) and Noonans syndrome are at increased risk for developing JMML [19,20] and up to 14% of cases of JMML occur in children with NF1.[21]

Granulocytic sarcoma (GS) (chloroma), describes extramedullary collections of leukemia cells. These collections can occur, albeit rarely, as the sole evidence of leukemia. In a review of 3 AML studies conducted by the former Children's Cancer Group (CCG), <1% of patients had isolated GS, and 11% had GS along with marrow disease at the time of diagnosis.[22] Importantly, the patient who presents with an isolated tumor, without evidence of marrow involvement, must be treated as if there is systemic disease. Patients with isolated GS have a good prognosis if treated with current AML therapy. For those patients who have GS in addition to marrow involvement, the patients with disease limited to the skin do worse than those without GS; those with AML that involves sites other than skin (e.g., orbit, head and neck), have a similar prognosis to patients with medullary leukemia alone. Many of these patients have t(8;21) with orbital myeloblastomas. The use of radiation therapy does not improve survival in patients with GS.[22]

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. Woods WG, Neudorf S, Gold S, et al.: A comparison of allogeneic bone marrow transplantation, autologous bone marrow transplantation, and aggressive chemotherapy in children with acute myeloid leukemia in remission. Blood 97 (1): 56-62, 2001.  [PUBMED Abstract]
   
   
3. Creutzig U, Ritter J, Zimmermann M, et al.: Improved treatment results in high-risk pediatric acute myeloid leukemia patients after intensification with high-dose cytarabine and mitoxantrone: results of Study Acute Myeloid Leukemia-Berlin-Frankfurt-Münster 93. J Clin Oncol 19 (10): 2705-13, 2001.  [PUBMED Abstract]
   
   
4. Stevens RF, Hann IM, Wheatley K, et al.: Marked improvements in outcome with chemotherapy alone in paediatric acute myeloid leukemia: results of the United Kingdom Medical Research Council's 10th AML trial. MRC Childhood Leukaemia Working Party. Br J Haematol 101 (1): 130-40, 1998.  [PUBMED Abstract]
   
   
5. Grier HE, Gelber RD, Camitta BM, et al.: Prognostic factors in childhood acute myelogenous leukemia. J Clin Oncol 5 (7): 1026-32, 1987.  [PUBMED Abstract]
   
   
6. Grimwade D, Walker H, Oliver F, et al.: The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children's Leukaemia Working Parties. Blood 92 (7): 2322-33, 1998.  [PUBMED Abstract]
   
   
7. Melnick A, Licht JD: Deconstructing a disease: RARalpha, its fusion partners, and their roles in the pathogenesis of acute promyelocytic leukemia. Blood 93 (10): 3167-215, 1999.  [PUBMED Abstract]
   
   
8. Tallman MS, Hakimian D, Kwaan HC, et al.: New insights into the pathogenesis of coagulation dysfunction in acute promyelocytic leukemia. Leuk Lymphoma 11 (1-2): 27-36, 1993.  [PUBMED Abstract]
   
   
9. Zipursky A, Poon A, Doyle J: Leukemia in Down syndrome: a review. Pediatr Hematol Oncol 9 (2): 139-49, 1992 Apr-Jun.  [PUBMED Abstract]
   
   
10. Homans AC, Verissimo AM, Vlacha V: Transient abnormal myelopoiesis of infancy associated with trisomy 21. Am J Pediatr Hematol Oncol 15 (4): 392-9, 1993.  [PUBMED Abstract]
    
    
11. Lange BJ, Kobrinsky N, Barnard DR, et al.: Distinctive demography, biology, and outcome of acute myeloid leukemia and myelodysplastic syndrome in children with Down syndrome: Children's Cancer Group Studies 2861 and 2891. Blood 91 (2): 608-15, 1998.  [PUBMED Abstract]
    
    
12. Athale UH, Razzouk BI, Raimondi SC, et al.: Biology and outcome of childhood acute megakaryoblastic leukemia: a single institution's experience. Blood 97 (12): 3727-32, 2001.  [PUBMED Abstract]
    
    
13. Raimondi SC, Chang MN, Ravindranath Y, et al.: Chromosomal abnormalities in 478 children with acute myeloid leukemia: clinical characteristics and treatment outcome in a cooperative pediatric oncology group study-POG 8821. Blood 94 (11): 3707-16, 1999.  [PUBMED Abstract]
    
    
14. Bennett JM, Catovsky D, Daniel MT, et al.: Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 51 (2): 189-99, 1982.  [PUBMED Abstract]
    
    
15. Mandel K, Dror Y, Poon A, et al.: A practical, comprehensive classification for pediatric myelodysplastic syndromes: the CCC system. J Pediatr Hematol Oncol 24 (7): 596-605, 2002.  [PUBMED Abstract]
    
    
16. Aricò M, Biondi A, Pui CH: Juvenile myelomonocytic leukemia. Blood 90 (2): 479-88, 1997.  [PUBMED Abstract]
    
    
17. Sanders JE, Buckner CD, Thomas ED, et al.: Allogeneic marrow transplantation for children with juvenile chronic myelogenous leukemia. Blood 71 (4): 1144-6, 1988.  [PUBMED Abstract]
    
    
18. Bunin N, Saunders F, Leahey A, et al.: Alternative donor bone marrow transplantation for children with juvenile myelomonocytic leukemia. J Pediatr Hematol Oncol 21 (6): 479-85, 1999 Nov-Dec.  [PUBMED Abstract]
    
    
19. 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]
    
    
20. Choong K, Freedman MH, Chitayat D, et al.: Juvenile myelomonocytic leukemia and Noonan syndrome. J Pediatr Hematol Oncol 21 (6): 523-7, 1999 Nov-Dec.  [PUBMED Abstract]
    
    
21. Niemeyer CM, Arico M, Basso G, et al.: Chronic myelomonocytic leukemia in childhood: a retrospective analysis of 110 cases. European Working Group on Myelodysplastic Syndromes in Childhood (EWOG-MDS) Blood 89 (10): 3534-43, 1997.  [PUBMED Abstract]
    
    
22. Dusenbery KE, Howells WB, Arthur DC, et al.: Extramedullary leukemia in children with newly diagnosed acute myeloid leukemia: a report from the Children's Cancer Group. J Pediatr Hematol Oncol 25 (10): 760-8, 2003.  [PUBMED Abstract]
    
    

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