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 ascopubs.org.
