Mega‐dose decitabine conditioning and prophylactic donor lymphocyte infusion for patients with relapsed/refractory AML with active disease at the time of allogeneic haematopoietic cell transplantation: A multicenter prospective phase II study

Summary Patients with relapsed/refractory acute myeloid leukaemia (R/R AML), especially those who failed in novel target agents are related to dismal survival. We developed a multi‐institutional, single‐arm, prospective phase II trial, to investigate intensified conditioning with ‘Mega‐Dose’ decitabine (MegaDAC) following allogeneic haematopoietic cell transplantation (allo‐HCT) for R/R AML. From 2019 to 2023, 70 heavily treated R/R AML patients in active disease were consecutively enrolled. Significantly, every patient ( n = 18) harbouring specific mutations exhibited no response to their best available target agents (BATs). Moreover, 74.3% of the enrolled patients did not reach remission following venetoclax‐based regimens. All patients underwent intravenous decitabine (400 mg/m 2 ) along with busulfan and cyclophosphamide. Median follow‐up was 26 months (8–65) after HCT. All engrafted patients achieved MRD negativity post‐HCT, with a median 3.3‐log reduction in recurrent genetic abnormalities. The regimen was well tolerated, without irreversible grades III–IV toxicity peri‐engraftment. The estimated 2‐year CIR was 29.6% (18.4%–41.7%) and the est‐2‐year NRM was 15.5% (7.8%–25.5%). The est‐2‐year LFS, OS, and GRFS were 55.0% (43.5%–69.4%), 58.6% (47.0%–73.0%), and 42.9% (31.9%–57.6%), respectively. Multivariate analysis showed that pre‐HCT drug exposures had no significant impact on primary outcomes. MegaDAC is highlighted as an effective and safe option for R/R AML in the new era of targeted therapies.