Allogeneic hematopoietic stem cell transplantation for pediatric acute myeloid leukemia in first complete remission: a meta-analysis

Abstract

Identification of pediatric patients with acute myeloid leukemia (AML) candidates to receive allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1) is still a matter of debate. Currently, transplantation is reserved to patients considered at high risk of relapse based on cytogenetics, molecular biology, and minimal residual disease (MRD) assessment. However, no randomized clinical trial exists in the literature comparing transplantation with other types of consolidation therapy. Here, we provide an up-to-date meta-analysis of studies comparing allo-HSCT in CR1 with chemotherapy alone as a post-remission treatment in high-risk pediatric AML. The literature search strategy identified 10 cohorts from 9 studies performing as-treated analysis. The quantitative synthesis showed improved overall survival (OS) (relative risk, 1.15; 95% confidence interval [CI], 1.06–1.24; P = 0.0006) and disease-free survival (relative risk, 1.31; 95% CI, 1.17–1.47; P = 0.0001) in the allo-HSCT group, with increased relapse rate in the chemotherapy group (relative risk, 1.26; 95% CI, 1.07–1.49; P = 0.006). Sensitivity analysis including prospective studies alone and excluding studies that reported the comparison only on intermediate-risk patients confirmed the benefit of allo-HSCT on OS. Further research should focus on individualizing allo-HSCT indications based on molecular stratification and MRD monitoring.

Children's Oncology Group's 2023 blueprint for research: Cellular therapy and stem cell transplantation

“…28 AAML1031: Allogeneic HCT from the best available donor improves survival for patients with AML who have high-risk cytogenetics or mutation profiles, such as Fms-like tyrosine kinase (FLT3) mutations. 29,30 Among other research questions, AAML1031 tested whether adding sorafenib, a tyrosine kinase inhibitor (TKI) that inhibits constitutively activated FLT3 during induction and maintenance would improve outcomes for patients with high allelic ratio (AR > 0.4) mutated FLT3. Patients who were not treated with sorafenib (n = 76) had worse DFS (HR 2.28, p = 0.032) than patients who were treated with sorafenib (n = 72).…”

Hematopoietic stem cell transplantation in Zagreb: the first 40 years

“…Myeloablative conditioning regimen combined with GVL reaction leads to favorable outcomes in patients with leukemia – a significant proportion have a chance to be cured or to become long-term disease-free survivors. There are numerous reports about HSCT efficiency in AML ( 31 - 33 ). One of the first prospective studies in AML was conducted by the Leukemia Group of the European Organization for Research and Treatment of Cancer (EORTC) ( 34 ).…”

Children’s Oncology Group’s 2023 Blueprint for Research: Cellular Therapy and Stem Cell Transplantation

“…28 AAML1031: Allogeneic HCT from the best available donor improves survival for patients with AML who have high-risk cytogenetics or mutation profiles, such as Fms-like tyrosine kinase (FLT3) mutations. 29,30 Among other research questions, AAML1031 tested whether adding sorafenib, a tyrosine kinase inhibitor (TKI) that inhibits constitutively activated FLT3 during induction and maintenance would improve outcomes for patients with high allelic ratio (AR >0.4) mutated FLT3. Patients who were not treated with sorafenib (n=76) had worse DFS (HR 2.28, p=0.032) than patients who were treated with sorafenib (n=72).…”