Reduced-toxicity conditioning regimens: A comparison of irradiation vs chemotherapy for the treatment of AML

Pretransplant conditioning is vital in patients with acute myeloid leukemia (AML) receiving allogeneic hematopoietic cell transplantation (allo-HCT) to provide immunoablation and avoid posttransplant graft rejection. Sebastian Giebel and colleagues recently published in Bone Marrow Transplantation, a retrospective study on the optimal conditioning for AML patients receiving allo-HCT.¹

The comparative study carried out by Giebel et al¹ describes the impact of total body irradiation (TBI) at the dose of 8 Gy combined with fludarabine (TBI8Gy/Flu) or busulfan at the dose of 9.6 mg/kg (3 days) with fludarabine (Bu3/Flu), on patients with AML.

During this study, lower doses of TBI8Gy/Flu (30% reduction) and Bu3/Flu (25% reduction) were used compared with classical myeloablative regimens. Moreover, cyclophosphamide was substituted by fludarabine. The transplant conditioning intensity score was reported to be in intermediate range (2.5).

The two treatments were evaluated based on their reduced-toxicity conditioning for patients with AML treated with allo-HCT. The primary endpoint was leukemia-free survival (LFS), and secondary endpoints comprised: overall survival (OS), relapse incidence, nonrelapse mortality (NRM), incidence of Grades II–IV acute graft-versus-host disease (GvHD), incidence of chronic GvHD, and survival-free from Grades III–IV acute GvHD, chronic GvHD, and relapse (GRFS).

Study design and data collection

Data was collected from > 600 transplant centers associated with the European Society for Blood and Marrow Transplantation (EBMT), which contained information on adult patients in first remission post allo-HCT with an intermediate or high-risk karyotype, but who did not have ex vivo T-cell depletion. There were two study arms:  Bu3/Flu, intravenous busulfan at a total dose of 9.6 mg/kg administered for 3 consecutive days with fludarabine (n = 350); and TBI8Gy/Flu, TBI at a total dose of 8 Gy in combination with fludarabine (n = 168).

Results

Median age for TBI8Gy/Flu patients was 50 years old, whereas the Bu3/Flu cohort contained patients in a significantly older age group. Also, the former group had a higher number of unrelated donors, as well as patients who received in vivo T-cell depletion. The median follow-up was 23 months for Bu3/Flu, and 57 months for TBI8Gy/Flu (Table 1).

Table 1. Patient, donor, and transplant-related characteristics and their significant differences¹

Figure 1. Outcomes of univariate analysis for a all patients, b treatment group ≤ 50 y.o., and c treatment group ≥ 50 y.o.¹

Data indicates a comparison between the BU3/Flu and TBI8Gy/Flu treatment groups.
*Marks significant difference in p values.
aGvHD, acute GvHD; cGvHD, chronic GvHD; GRFS, survival-free from relapse, acute GvHD Grades III and IV, and chronic GvHD; GvHD, graft-versus-host disease; LFS, leukemia-free survival; NRM, nonrelapse mortality; OS, overall survival; RI, relapse incidence; y.o., years old. 

Interaction between age and type of conditioning