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Postremission Therapy for AML

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    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]

    Many, but not all, pediatric clinical trial groups prescribe allogeneic HSCT for high-risk patients in first remission.[19] For example, the Children's Oncology Group (COG) frontline AML clinical trial (COG-AAML1031) prescribes allogeneic HSCT in first remission only for patients with predicted high risk of treatment failure based on unfavorable cytogenetic and molecular characteristics and elevated end-of-induction MRD levels. On the other hand, the AML-BFM 2004 clinical trial restricts allogeneic HSCT to patients in second CR and to refractory AML based on results from their AML-BFM 98 study showing no improvement in DFS or OS for high-risk patients receiving allogeneic HSCT in first CR.[17] Additionally, late sequelae (e.g., cardiomyopathy, skeletal anomalies, and liver dysfunction or cirrhosis) were increased for children undergoing allogeneic HSCT in first remission on the AML-BFM 98 study.[17] Because definitions of high-, intermediate-, and low-risk AML are evolving due to the ongoing association of molecular characteristics of the tumor with outcome (e.g., FLT-3 internal tandem duplications, WT1 mutations, and NPM1 mutations) as well as response to therapy (e.g., MRD assessments postinduction therapy), further analysis of subpopulations of patients treated with allogeneic HSCT will be an ongoing need in current and future clinical trials.

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