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

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Current application of allogeneic HSCT involves incorporation of risk classification into the determination of whether transplantation should be pursued in first remission. Because of the improved outcome in patients with favorable prognostic features receiving contemporary chemotherapy regimens and the lack of demonstrable superiority for HSCT in this patient population, it is now recommended that this group of patients receive MFD HSCT only after first relapse and the achievement of a second complete remission (CR).[9,12,19,20]

There is conflicting evidence regarding the role of allogeneic HSCT in first remission for patients with intermediate-risk characteristics:

  • A study combining the results of the POG-8821, CCG-2891, COG-2961, and MRC-Leuk-AML-10-Child studies identified a DFS and OS advantage for allogeneic HSCT in patients with intermediate-risk AML but not favorable-risk (inv(16) and t(8;21)) or poor-risk (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.[12] Weaknesses of this study include the large percentage of patients not assigned to a risk group and the relatively low EFS and OS rates for patients with intermediate risk assigned to chemotherapy compared with results observed in more recent clinical trials.[7,21]
  • The AML99 clinical trial from the Japanese Childhood AML Cooperative Study Group observed a significant difference in DFS for intermediate risk patients assigned to MFD HSCT, but there was not a significant difference in OS.[22]
  • The AML-BFM 99 clinical trial demonstrated no significant difference for intermediate risk patients in either DFS or OS for patients assigned to MFD HSCT versus those assigned to chemotherapy.[18]

Given the improved outcome for patients with intermediate-risk AML in recent clinical trials and the burden of acute and chronic toxicities associated with allogeneic transplantation, many childhood AML treatment groups (including the Children's Oncology Group [COG]) employ chemotherapy for intermediate-risk patients in first remission and reserve allogeneic HSCT for use following potential relapse.[7,22,23]

There are conflicting data regarding the role of allogeneic HSCT in first remission for patients with high-risk disease, complicated by the differing definitions of high risk used by different study groups.

  • A retrospective analysis from COG and Center for International Blood and Marrow Transplant Research (CIBMTR) data on patients with AML and high-risk cytogenetics, defined as monosomy 7/del(7q), monosomy 5/del(5q), abnormalities of 3q, t(6;9), or complex karyotypes comparing chemotherapy only with minimal residual disease (MRD) donor and matched-unrelated donor (MUD) stem cell transplantation demonstrated no difference in the 5-year OS among the three treatment groups.[24]
  • A Nordic Society for Pediatric Hematology and Oncology study reported that time-intensive reinduction therapy followed by transplant with best available donor for patients whose AML did not respond to induction therapy resulted in 70% survival at a median follow-up of 2.6 years.[25][Level of evidence: 2A]
  • A single-institution retrospective study of 50 consecutive patients (aged 0–30 years) with high-risk AML (FLT3-ITD, 11q23 MLL rearrangements, presence of chromosome 5 or 7 abnormalities, induction failure, persistent disease) reported a 5-year 72% OS and a 69% leukemia-free survival; they also reported a 17% treatment-related mortality.[26]
  • A subgroup analysis from the AML-BFM 98 clinical trial demonstrated improved survival rates for patients with 11q23 aberrations allocated to allogeneic HSCT, but not for patients without 11q23 aberrations.[18]
  • For children with FLT3-ITD (high allelic ratio), those who received MFD HSCT (n = 6) had higher OS than who received standard chemotherapy (n = 28); however the number of cases studied limited the ability to draw conclusions.[27]
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