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Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Postremission Therapy for AML

A major challenge in the treatment of children with acute myeloid leukemia (AML) is to prolong the duration of the initial remission with additional chemotherapy or hematopoietic stem cell transplantation (HSCT). In practice, most patients are treated with intensive chemotherapy after remission is achieved, as only a small subset have a matched-family donor (MFD). Such therapy includes some of the drugs used in induction while also introducing non-cross-resistant drugs and commonly high-dose cytarabine. Studies in adults with AML have demonstrated that consolidation with a high-dose cytarabine regimen improves outcome compared with consolidation with a standard-dose cytarabine regimen, particularly in patients with inv(16) and t(8;21) AML subtypes.[1,2] Randomized studies evaluating the contribution of high-dose cytarabine to postremission therapy have not been conducted in children, but studies employing historical controls suggest that consolidation with a high-dose cytarabine regimen improves outcome compared with less intensive consolidation therapies.[3,4,5]

The optimal number of postremission courses of therapy remains unclear, but appears to require at least three courses of intensive therapy, including the induction course.[6] A United Kingdom Medical Research Council (MRC) study randomly assigned adult and pediatric patients to four versus five courses of intensive therapy. Five courses did not show an advantage in relapse-free and overall survival (OS).[7,8][Level of evidence: 1iiA]

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The use of HSCT in first remission has been under evaluation since the late 1970s, and evidence-based appraisals concerning indications for autologous and allogeneic HSCT have been published.[9] Prospective trials of transplantation in children with AML suggest that overall 60% to 70% of children with HLA-matched donors available who undergo allogeneic HSCT during their first remission experience long-term remissions,[10,11] with the caveat that outcome following allogeneic HSCT is dependent upon risk-classification status.[12] In prospective trials of allogeneic HSCT compared with chemotherapy and/or autologous HSCT, a superior disease-free survival (DFS) has been observed for patients who were assigned to allogeneic transplantation based on availability of a family 6/6 or 5/6 HLA-matched donor in adults and children.[10,11,13,14,15,16,17] However, the superiority of allogeneic HSCT over chemotherapy has not always been observed.[18] Several large cooperative group clinical trials for children with AML have found no benefit for autologous HSCT over intensive chemotherapy.[10,11,13,15]

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