Frontline allo-SCT in MRD-negative, intermediate-risk AML Open Access

TO THE EDITOR:

We read with great interest the publication by Jen et al¹ in the issue of Blood Advances which published on 25 February 2025. In this study, Jen et al report a single-institution analysis of the impact of measurable residual disease (MRD) clearance kinetics in patients with acute myeloid leukemia (AML) undergoing intensive chemotherapy. A notable finding was that patients in the European LeukemiaNet (ELN) 2022 intermediate-risk category who achieved early MRD negativity seemed to benefit from allogeneic stem cell transplantation (allo-SCT) in first complete remission (CR1), given that those who did not undergo allo-SCT in CR1 had markedly inferior relapse-free survival and overall survival (OS).

These results are of practical importance and contribute to the unsettled debate on whether intermediate-risk patients who achieve an MRD-negative response can safely forgo transplantation in CR1.² In this respect, a pooled analysis from the National Cancer Research Institute AML17 and AML19 trials showed overlapping OS among patients with NPM1/FLT3-ITD comutated AML who attained molecular MRD-negative status after 2 courses of induction chemotherapy, regardless of whether they underwent allo-SCT in CR1.³ Consistent with these data, no differences in OS were reported among patients with intermediate-risk AML, as defined by the Medical Research Council 2010 criteria, who were randomized to receive either standard consolidation chemotherapy or allo-SCT in CR1 in the non-MRD—guided ETAL-1 randomized trial.⁴ Of note, similar results were observed in the ELN 2017 intermediate-risk subgroup. Most importantly, a significant fraction of patients in the non–CR1-allo-SCT arm could be spared from transplantation in each of these cohorts. Despite a substantially higher risk of relapse in the non–CR1-allo-SCT arms, a common theme of these 2 studies was the high success rate in bridging relapsing patients to transplantation; remarkably, in the ETAL-1 trial, all relapsing patients underwent allo-SCT, with half of them not receiving previous salvage therapy. Conceivably, the ability to reach allo-SCT after relapse may be further improved by the expanding therapeutic armamentarium for AML—even without factoring in recent randomized data that cast doubt on the impact of remission induction in this setting.⁵ These data suggest that an aggressive approach to transplantation after relapse may prevent expected gaps in relapse-free survival from translating into differences in OS between the 2 strategies.

Given the discordant findings in the report by Jen et al, some important information not provided could help better interpret these results. First, it would be of interest to know whether certain MRD^neg/neg patient subgroups were preferentially referred (or not) to allo-SCT in CR1 and whether the transplant vs no-transplant arms differed in relevant characteristics, reflecting possible selection biases. Second, it would also be clarifying to report how many patients relapsing in the MRD^neg/neg non–CR1-allo-SCT group achieved a second remission and the transplantation rate in this cohort. Finally, it might be informative to further assess the robustness of differences between arms, given that the shown landmark analysis is expected to only partially control for immortal time bias.

With results from the RESOLVE trial still far off, retrospective data such as this study will be key to informing our current clinical practice.

Contribution: E.R.-A. drafted the manuscript; and T.C.-V., C.M.-C., and J.A.P.-S. reviewed the manuscript and provided critical feedback.

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Correspondence: Eduardo Rodríguez-Arbolí, Department of Hematology, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBiS/CSIC), University of Seville, Avenida Manuel Siurot s/n, 41013 Seville, Spain; email: eduardo.rodriguez.arboli.sspa@juntadeandalucia.es.