Comparison of Conditioning Treatments in Patients With AML Undergoing HLA-Haploidentical Hematopoietic Stem Cell Transplant

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In a Chinese phase III trial reported in the Journal of Clinical Oncology, Ling et al found that conditioning with busulfan/fludarabine resulted in reduced transplantation-related mortality vs busulfan/cyclophosphamide in patients with acute myeloid leukemia (AML) undergoing human leukocyte antigen (HLA)-haploidentical hematopoietic stem cell transplantation (haplo-HCT).

As stated by the investigators, “The busulfan/fludarabine conditioning regimen has lower transplantation-related mortality than busulfan/cyclophosphamide in HLA-matched transplantation. We aimed to compare outcomes of the busulfan/fludarabine regimen with those of the busulfan/cyclophosphamide regimen in haplo-HCT.”

Study Details

In the multicenter open-label trial, 386 patients were randomly assigned between November 2015 and September 2019 to receive busulfan/fludarabine (n = 194), consisting of busulfan at 0.8 mg/kg four times per day on days –6 to –3 and fludarabine at 30 mg/m2 once daily on days –7 to –3, or busulfan/cyclophosphamide (n = 192), consisting of the same dose of busulfan and cyclophosphamide at 60 mg/kg once daily on days –3 and –2. The primary endpoint was 1-year transplantation-related mortality in the intention-to-treat population.

Key Findings

Median follow-up was 55.0 months (interquartile range = 46.5–69.0 months). Transplantation-related mortality at 1 year was 7.2% (95% confidence interval [CI] = 4.1%–11.4%) in the busulfan/fludarabine group vs 14.1% (95% CI = 9.6%–19.4%) in the busulfan/cyclophosphamide group (hazard ratio [HR] = 0.51, 95% CI = 0.27–0.97, P = .041).

The 5-year relapse rate was 17.9% (95% CI = 9.6%–28.3%) in the busulfan/fludarabine group vs 14.2% (95% CI = 9.1%–20.5%) in the busulfan/cyclophosphamide group (HR = 1.12, 95% CI = 0.65–1.95, P = .670). Overall survival at 5 years was 72.5% (95% CI = 62.2%–80.4%) in the busulfan/fludarabine group vs 68.2% (95% CI = 58.9%–75.9%) in the busulfan/cyclophosphamide group (HR = 0.84, 95% CI = 0.56–1.26, P =.465).

Among patients in the per-protocol population, grade ≥ 3 regimen-related toxicity was reported in 0 (0%) of 191 patients in the busulfan/fludarabine group vs 9 (4.7%) of 190 patients in the busulfan/cyclophosphamide group (P = .002). The most common any-grade regimen-related toxicity was stomatitis in both groups (45.5% vs 71.1%). Irrespective of causal attribution, grade ≥ 3 adverse events occurred in 68.1% vs 77.4% of patients (P = .041), most commonly infections (47.6% vs 48.4%) and acute graft-vs-host disease (22.0% vs 23.7%).

The investigators concluded, “The busulfan/fludarabine regimen has a lower transplantation-related mortality and regimen-related toxicity and similar relapse for patients with AML undergoing haplo-HCT compared with the busulfan/cyclophosphamide regimen.”

Qifa Liu, MD, of the Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the National Natural Science Foundation of China, National Key Research and Development Program of China, and others. For full disclosures of the study authors, visit

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