Decitabine plus busulfan-cyclophosphamide versus busulfan-cyclophosphamide myeloablative conditioning before allogeneic haematopoietic stem cell transplantation for reducing risk of relapse in adult KMT2A‑rearranged leukaemia in China: an open-label, multicentre, randomised phase 3 trial

Key numbers

• 95% CI 6-22

Background An unmet need persists for optimal myeloablative conditioning before allogeneic haematopoietic stem cell transplantation (HSCT) in adult KMT2A‑rearranged leukaemia. We investigated whether decitabine plus busulfan-cyclophosphamide (DAC-BuCy) conditioning reduced the risk of relapse compared with busulfan-cyclophosphamide (BuCy) conditioning. Methods In this open-label, randomised, phase 3 trial at eight transplantation centres in China, eligible patients were aged 14-65 years, had morphologically confirmed KMT2A-rearranged leukaemia, and had an Eastern Cooperative Oncology Group performance status of 0-2. Patients were randomly assigned (1:1) before HSCT to DAC-BuCy (intravenous decitabine 20 mg/m2 once a day on days -14 to -10, intravenous busulfan 3·2 mg/kg once a day on days -7 to -4, and intravenous cyclophosphamide 60 mg/kg once a day on days -3 to -2) or BuCy (same dose and duration of busulfan and cyclophosphamide). Randomisation was done with permuted blocks (block size four) with no stratification and was implemented through an independent, interactive, web-based response system. The primary endpoint was 2-year cumulative incidence of relapse in the intention-to-treat population. Safety was assessed in all patients who received treatment. This trial is registered with ClinicalTrials.gov (NCT03596892) and is complete. Findings Between May 1, 2019, and Jan 31, 2023, 130 patients were randomised to receive a DAC-BuCy (n=65; 34 [52%] female and 31 [48%] male) or BuCy (n=65; 29 [45%] female and 36 [55%] male) regimen. Median follow-up was 34·7 months (IQR 30·2-52·5). 2-year cumulative incidence of relapse was 12% (95% CI 6-22) in the DAC-BuCy group and 29% (19-41) in the BuCy group (hazard ratio 0·41 [0·20-0·87]; p=0·017). The most common grade 3-5 adverse events were infections or infestations (DAC-BuCy group 27 [42%] and BuCy group 25 [38%]), acute graft-versus-host disease (DAC-BuCy group 23 [35%] and BuCy group 22 [34%]), and gastrointestinal disorders (DAC-BuCy group 14 [22%] and BuCy group 15 [23%]). Four (6%) patients in the DAC-BuCy group and five (8%) patients in the BuCy group died from adverse events, of which two were due to regimen-related toxicities: one nervous system disorder in the DAC-BuCy group and one cardiac disorder in the BuCy group. Interpretation The addition of decitabine to BuCy conditioning reduced the risk of relapse with an acceptable safety profile in adult patients with KMT2A‑rearranged leukaemia and could be a suitable therapeutic option for this population. Funding The National Natural Science Foundation of China, the National Key Research and Development Program of China, the Science and Technology Program of Guangdong Province, the Non-communicable Chronic Diseases-National Science and Technology Major Project, the Natural Science Foundation of Guangdong Province, the Science and Technology Planning Project of Guangzhou, and the Outstanding Youth Cultivation Program of Nanfang Hospital, Southern Medical University. Translation For the Chinese translation of the abstract see Supplementary Materials section.

Zhongli Hu, Zhiping Fan, Min Dai, Hai He, Hua Jin, Zhiqiang Sun, Fen Huang, Na Xu, Qianwei Liu, Yiqing Li, Ying Dong, Ping Zhu, Can Liu, Yunxin Zeng, Jing Sun, Ruijuan Sun, Li Xuan, Qifa Liu

Leverage2 / 5

Reusable within one subfield (a technique, dataset, or protocol a few groups will adopt).

10% of this desk’s rubric

Magnitude3 / 5

Large gain: roughly 2x, or a clear new state of the art on a hard, unsaturated problem.

20% of this desk’s rubric

Evidence5 / 5

Definitive: phase 3 randomized evidence on hard endpoints, multi-lab replication, or community verification at scale.

32% of this desk’s rubric

Novelty3 / 5

A genuinely new approach to an open problem.

8% of this desk’s rubric

Trajectory2 / 5

Some room to improve with obvious engineering.

5% of this desk’s rubric

Stakes3 / 5

Meaningful benefit to many people within a few years.

25% of this desk’s rubric

• Citations0 (reference 20, via openalex, Nov 1, 2026, 06:17 UTC)

• Reviewed by heuristic-v10 on Nov 1, 2026, 06:17 UTC. Paper type: clinical.
• Categories: Clinical Trial, Phase III, Multicenter Study, Randomized Controlled Trial, Journal Article, Humans, Leukemia, Recurrence, Busulfan, Cyclophosphamide, Histone-Lysine N-Methyltransferase
• LEAD, No.1 in the Front page edition of November 1, 2026.
• LEAD, No.1 in the Medicine edition of November 1, 2026.