The value of repeated molecular testing early after HCT highlighted

Findings from a retrospective, multicentre study underscore the importance of intensified molecular monitoring in patients with acute myeloid leukaemia (AML) early after allogeneic hematopoietic stem cell transplantation (allo-HCT). Early relapse emerged as the strongest predictor of poor prognosis, while increased mutational complexity was associated with a higher risk of early relapse [1].

Relapse following allo-HCT remains a major clinical challenge in AML and is associated with poor outcomes. To better characterise the mutational and clonal dynamics underlying relapse, 57 adult AML patients from 3 centres in Germany, Greece, and Canada who relapsed after allo-HCT were analysed. Study presenter, researcher Dr Kristina Maas-Bauer (University of Freiburg, Germany), explained that the molecular analyses performed may improve the prediction of early relapse (<6 months post-HCT) and help guide therapeutic decision-making.

Dr Maas-Bauer and colleagues performed paired next-generation sequencing (NGS) myeloid panels analyses (38–84 genes) at diagnosis/pre-HCT and again at relapse. The median patient age was 52.5 years (range 18-71). More than half of patients (54%) had adverse-risk AML according to ELN classification, while 25% had refractory disease prior to transplantation.

AML relapse following allo-HCT demonstrated substantial genetic and clonal instability. Overall, 68% of patients showed acquisition or loss of mutations, predominantly involving FLT3-ITD, NRAS, and KRAS, highlighting recurrent activation of proliferative and survival signalling pathways. In contrast, founder mutations in DNMT3A and TP53 were frequently retained. Distinct relapse evolution patterns, including constant, linear, branching, and parallel evolution, were not predictive of relapse risk and did not influence overall survival (OS) or progression-free survival (PFS).

By contrast, relapse occurring within the first 6 months after allo-HCT was identified as a strong independent predictor of poor OS (P=0.049). Furthermore, increased mutational burden at diagnosis independently predicted early relapse (OR 1.84; 95% CI 1.02–3.33; P=0.04), potentially reflecting rapid expansion of pre-existing dominant clones.

Dr Maas-Bauer noted that the unfavourable baseline characteristics of the study population may also have contributed to the poor survival outcomes, independent of clonal evolution or mutational patterns. Overall, these findings emphasise the importance of repeated molecular proﬁling, particularly during the first 6 months after transplantation. For measurable residual disease assessment, persistent mutations may represent the preferred molecular targets.

Maas-Bauer C, et al. Mutational landscape changes of AML in patients relapsing after allogeneic hematopoietic cell transplantation. A342, EBMT congress 2026, 22-25 March, Madrid, Spain.