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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 to 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] 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.[10,11,12,13,14,15,16] However, the superiority of allogeneic HSCT over chemotherapy has not always been observed.[17] Several large cooperative group clinical trials for children with AML have found no benefit for autologous HSCT over intensive chemotherapy.[10,11,12,14]

Because of the improved outcome in patients with favorable prognostic features receiving contemporary regimens, it is now recommended that this group of patients receive an MFD HSCT only after first relapse and the achievement of a second complete remission (CR).[9,18,19]

While there is a clear movement away from transplantation in first remission using matched family donors in pediatric patients with AML that has favorable prognostic features, there is evidence suggesting an advantage for allogeneic HSCT in patients with intermediate-risk characteristics. A large intent-to-treat analysis of 472 young adults treated on Bordeaux Grenoble Marseille Toulouse (BGMT) studies showed a survival benefit from allogeneic HSCT in intermediate-risk patients (all patients not favorable or unfavorable), while patients with favorable-risk disease (t(15;17), t(8:21), or inv(16)) did not appear to benefit. Of note, there were insufficient numbers in the study to determine whether patients with unfavorable-risk disease (complex karyotype (≥5 cytogenetic findings), del(5q), monosomy 5 or 7, 3q rearrangements, t(9;22), t(6;9), or 11q23 rearrangements, except t(9;11)) benefit from this approach.[20] A second study combining the results of the POG-8821, CCG-2891, COG-2961, and MRC-Leuk-AML-10-Child studies confirmed an advantage for allogeneic HSCT in patients with intermediate-risk AML but not favorable-risk as defined above or poor-risk as defined below. However, again, there were insufficient numbers in this study to assess the role of matched family member transplantation in patients with poor-risk AML, defined by del(5q), monosomy 5 or 7, or more than 15% blasts after first induction for POG/CCG studies as well as including 3q abnormalities and complex cytogenetics in the MRC study.[21]


WebMD Public Information from the National Cancer Institute

Last Updated: February 25, 2014
This information is not intended to replace the advice of a doctor. Healthwise disclaims any liability for the decisions you make based on this information.
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