PURPOSE A previous study by the International Berlin-Frankfurt-Münster Study Group (I-BFM-SG) on childhood KMT2A-rearranged ( KMT2A-r) AML demonstrated the prognostic value of the fusion partner. This I-BFM-SG study investigated the value of flow cytometry-based measurable residual disease (flow-MRD) and evaluated the benefit of allogeneic stem-cell transplantation (allo-SCT) in first complete remission (CR1) in this disease. METHODS A total of 1,130 children with KMT2A-r AML, diagnosed between January 2005 and December 2016, were assigned to high-risk (n = 402; 35.6%) or non–high-risk (n = 728; 64.4%) fusion partner-based groups. Flow-MRD levels at both end of induction 1 (EOI1) and 2 (EOI2) were available for 456 patients and were considered negative (<0.1%) or positive (≥0.1%). End points were 5-year event-free survival (EFS), cumulative incidence of relapse (CIR), and overall survival (OS). RESULTS The high-risk group had inferior EFS (30.3% high risk v 54.0% non-high risk; P < .0001), CIR (59.7% v 35.2%; P < .0001), and OS (49.2% v 70.5%; P < .0001). EOI2 MRD negativity was associated with superior EFS (n = 413; 47.6% MRD negativity v n = 43; 16.3% MRD positivity; P < .0001) and OS (n = 413; 66.0% v n = 43; 27.9%; P < .0001), and showed a trend toward lower CIR (n = 392; 46.1% v n = 26; 65.4%; P = .016). Similar results were obtained for patients with EOI2 MRD negativity within both risk groups, except that within the non–high-risk group, CIR was comparable with that of patients with EOI2 MRD positivity. Allo-SCT in CR1 only reduced CIR (hazard ratio, 0.5 [95% CI, 0.4 to 0.8]; P = .00096) within the high-risk group but did not improve OS. In multivariable analyses, EOI2 MRD positivity and high-risk group were independently associated with inferior EFS, CIR, and OS. CONCLUSION EOI2 flow-MRD is an independent prognostic factor and should be included as risk stratification factor in childhood KMT2A-r AML. Treatment approaches other than allo-SCT in CR1 are needed to improve prognosis.

Introduction: Survival rates of pediatric acute myeloid leukemia (AML) in low-and middle-income countries (LMICs) seem extremely poor, and the available literature on the matter is scarce. Accordingly, there is a limited understanding of poor treatment outcomes seen in this population. Areas covered: We provide an overview of the available literature with respect to treatment outcomes of pediatric AML in LMICs yielding poor outcomes compared to high-income countries. Moreover, treatment outcomes vary markedly between LMICs. In addition, there is a wide variation among studies in how treatment outcomes are reported and analyzed. Expert opinion: The substantially inferior treatment outcomes of pediatric AML in LMICs emphasize the unprecedented importance of global initiatives and international collaborations to improve the survival of these patients. A coordinated approach is necessary to carry out country-specific situational analyses. These analyses will result in operational plans on how to structurally implement childhood cancer registries, align healthcare infrastructure, build on capacities, and provide universal health coverage in LMICs. In addition, we strongly recommend that, in the future, LMICs document, analyze, and publish pediatric AML treatment outcomes in a more structured and uniform manner.