Background: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a standard of care for patients with high risk acute myeloid leukemia (AML). However, the procedure using conventional myeloablative conditioning regimens based on either busulphan (Bu) or total body irradiation (TBI) in combination with cyclophosphamide is associated with significant risk of non-relapse mortality (NRM). The use of reduced-intensity conditioning regimens results in improved tolerance but increased incidence of disease recurrence. In order to reduce toxicity while maintaining the anti-leukemic efficacy alternative conditioning regimens have been proposed including the use of Bu or TBI in combination with fludarabine (Flu). The goal of this retrospective, multicenter study was thus to compare Bu4Flu and TBI12Gy/Flu.
Patients and methods: Adult patients with AML treated with alloHSCT from either HLA-matched sibling (MSD) or unrelated donor (URD) between year 2012 and 2017 were included in the analysis. The following conditioning regimens have been selected for the comparison: intravenous Bu at the total dose 12.8 mg/kg (4 days) + Flu (Bu4Flu, N=60) or TBI at the total dose of 12 Gy given in three fractions + Flu (TBI12Flu, N=40).
Results: 100 patients (Bu4Flu, n=60; TBI4Flu, n=40) were included in the analysis. Median age was 42 (19-62) years in Bu4Flu group and 36 (19-64) for TBI12Flu group (p=0.01). Proportion of patients given transplant from URD was 72% and 70%, respectively (p=NS). The rates of patients treated with HSCT CR1, CR>1 and active disease were 75%, 25%, 0% in the Bu4Flu group while 82.5%, 10% and 7% in the TBI12Flu group (p=NS).
All patients engrafted except for one patient in the TBI12Flu group who died of infection before engraftment. Time to neutrophil recovery was significantly faster after TBI12Flu (median 15 days, range 11-24) compared to Bu4Flu (18, 12-36 days) (p=0.000007). With the median follow up of 18 months, the cumulative incidence of relapse at 2 years was 11% (+/-6) and 30% (+/-7), respectively (p=0.14) while NRM was 19% (+/-8) and 10 (+/-5%), respectively (p=0.34). The probability of OS was 76% (+/-8) after TBI12Flu and 71% (+/-7%) after Bu4Flu (p=0.69). The LFS rates were 70% (+/-8%) and 60% (+/-7%), respectively (p=0.53). No signficant differences regarding survival could be detected in analysis restricted to patients transplanted in CR.
Conclusion: Both Bu4Flu or TBI12Flu as conditioning regimens pre-alloHSCT for patients with AML are highly effective, which together with acceptable tolerance leads to survival rates of more than 70% at two years. TBI12Flu is associated with faster engraftment and a tendency to reduced risk of relapse. Prospective studies comparing both regiemens are needed.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.