Patients with acute myeloid leukemia (AML) undergoing HLA-haploidentical hematopoietic cell transplantation (haplo-HCT) have a lower transplant-related mortality (TRM) and similar relapse rates with the busulfan plus fludarabine (BuFlu) conditioning regimen compared with the busulfan plus cyclophosphamide (BuCy) conditioning regimen, according to research published in the Journal of Clinical Oncology.

Researchers in China conducted a multicenter, open-label, randomized phase 3 trial comparing outcomes of the BuFlu regimen with those of the BuCy regimen in adult patients (18-65 years) with AML undergoing haplo-HCT ( Identifier: NCT02487069).

Between November 20, 2015, and September 30, 2019, patients were randomly assigned (1:1) to receive BuFlu (busulfan 0.8 mg/kg, 4 times per day on days -6 to -3; fludarabine 30 mg/m2, 1 time per day on days -7 to -3) or BuCy (same busulfan dosage; cyclophosphamide 60 mg/kg 1 time per day on days -3 and -2). The primary endpoint was 1-year TRM (intention-to-treat population) and safety (per-protocol population).

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A total of 386 patients were randomized, 194 to the BuFlu arm (median age, 37.0 years; interquartile range [IQR], 29.0-43.0) and 192 to the BuCy arm (median age, 35.0 years; IQR, 28.0-43.0). The median follow-up duration was 55.0 months (IQR, 46.5-69.0).

The 1-year TRM rate was significantly lower in the BuFlu arm compared with the BuCy arm (7.2%; 95% CI, 4.1-11.4; vs 14.1%; 95% CI, 9.6-19.4; hazard ratio [HR], 0.51; 95% CI, 0.27-0.97; P =.041).

The 5-year relapse (17.9%; 95% CI, 9.6-28.3; vs 14.2%; 95% CI, 9.1-20.5; HR, 1.12; 95% CI, 0.65-1.95; P =.670) and the 5-year overall survival rates (72.5%; 95% CI, 62.2-80.4; vs 68.2%; 95% CI, 58.9-75.9; HR, 0.84; 95% CI, 0.56-1.26; P =.465) were similar between the arms.

Grade 3 regimen-related toxicity was reported for 0% of the BuFlu arm and 4.7% of the BuCy arm (P =.002). Grade 3-5 adverse events were reported for 68.1% of the BuFlu arm and 77.4% of the BuCy arm (P =.041).

“Our results support that, compared with the standard BuCy regimen, the BuFlu regimen has a lower TRM, similar relapse, and a trend of better survival for patients with AML undergoing haplo-HCT. The BuFlu regimen should be recommended as an alternative one in haplo-HCT for patients with AML,” concluded the researchers.

Limitations of the study included the unblinded and nonplacebo-controlled design and the relatively younger median age of the patients.


Ling Y, Xuan L, Xu N, et al. Busulfan plus fludarabine compared with busulfan plus cyclophosphamide for AML undergoing HLA-haploidentical hematopoietic cell transplantation: a multicenter randomized phase III trial. J Clin Oncol. Published online June 19, 2023. doi:10.1200/JCO.23.00101