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Summary: NPM1‐mutated acute myeloid leukaemia (NPM1mut AML) represents a mostly favourable/intermediate risk disease that benefits from allogeneic haematopoietic stem cell transplantation (HSCT) in case of measurable residual disease (MRD) relapse or persistence after induction chemotherapy. Although the negative prognostic role of pre‐HSCT MRD is established, no recommendations are available for the management of peri‐transplant molecular failure (MF). Based on the efficacy data of venetoclax (VEN)‐based treatment in NPM1mut AML older patients, we retrospectively analysed the off‐label combination of VEN plus azacitidine (AZA) as bridge‐to‐transplant strategy in 11 NPM1mut MRD‐positive fit AML patients. Patients were in MRD‐positive complete remission (CRMRDpos) at the time of treatment: nine in molecular relapse and two in molecular persistence. After a median number of two cycles (range 1–4) of VEN–AZA, 9/11 (81.8%) achieved CRMRD‐negative (CRMRDneg). All 11 patients proceeded to HSCT. With a median follow‐up from treatment start of 26 months, and a median post‐HSCT follow‐up of 19 months, 10/11 patients are alive (1 died from non‐relapse mortality), and 9/10 patients are in MRDneg status. This patient series highlights the efficacy and safety of VEN–AZA to prevent overt relapse, achieve deep responses and preserve patient fitness before HSCT, in patients with NPM1mut AML in MF. [ABSTRACT FROM AUTHOR]