Long-term outcomes of total body irradiation plus cyclophosphamide versus busulfan plus cyclophosphamide as conditioning regimen for acute lymphoblastic leukemia: a comparative study

Abstract

The role of total body irradiation (TBI) in allogeneic hematopoietic stem cell transplantation (HCT) for adult acute lymphoblastic leukemia (ALL) remains controversial. Therefore, we investigated long-term treatment outcomes of transplanted ALL patients aiming to identify prognostic factors and the impact of conditioning. We enrolled consecutive ALL patients transplanted from 1990 to 2016, following TBI- or busulfan (Bu)-based conditioning regimen. We studied 151 ALL patients transplanted in first complete remission (CR) (60), other CR (33), or relapsed/refractory disease (58) from sibling (87), and HLA-matched (42) or mismatched (17) unrelated and alternative donors (5). High-dose fractionated TBI-based conditioning was administered in 84. No differences were observed in baseline characteristics, except for disease stage at transplant, donor type, and graft source. With a follow-up of 19.0 (0.5-170.5) in TBI and 14.5 (1.2-319.1) months in non-TBI patients, there was no difference in acute (grades II-IV) or chronic GVHD, thrombotic microangiopathy, and bacterial or fungal infections. Only viral infections were significantly increased in the non-TBI group. There was no significant difference in the cumulative incidence (CI) of treatment-related or relapse mortality and disease-free or overall survival (OS). In the multivariate analysis, unfavorable pre-transplant predictors of OS were age (p = 0.024), advanced disease stage (p = 0.007), and female-to-male donor (p = 0.006). Interestingly, TBI patients younger than 40 years had significantly higher OS (55.1%, p = 0.023) and DFS (48.6%, p = 0.020). In conclusion, high-dose TBI is feasible in younger patients providing better survival. The choice between TBI- or Bu-conditioning regimens remains challenging.

Transplant‐associated thrombotic microangiopathy: Incidence, prognostic factors, morbidity, and mortality in allogeneic hematopoietic cell transplantation

“…In addition to the present larger study, we had also found a univariate association between TA‐TMA and TBI‐based conditioning in a smaller study of TA‐TMA in our population . It should be noted that TBI‐based conditioning has shown excellent results of survival and safety in our center, especially in patients younger than 40 years of age, as previously described . Other clinical predictors under consideration are infections.…”

A New Era in Endothelial Injury Syndromes: Toxicity of CAR-T Cells and the Role of Immunity

“…SOS/VOD disease of the liver has been traditionally considered a severe complication of allogeneic HCT, particularly in patients with known risk factors [42]. Although it manifests as a rare HCT complication thanks to advances in transplant modalities [43,44], calicheamicin-conjugated antibodies, gemtuzumab and inotuzumab ozogamicin, have led to renewed interest in this syndrome [45,46]. Our group along with others has shown that changes in coagulation and fibrinolysis are predictive of SOS/VOD [47].…”

New Approaches to Allogeneic Haematopoietic Cell Transplantation

“…100 In patients younger than 40 years, TBI provides better 5-year OS (55.1%, p=0.023) and disease-free survival (DFS) (48.6%, p=0.020) outcomes than busulfan-based conditioning regimens. 101 The EBMT Acute Leukaemia Working Party showed that the combination of TBI with etoposide is as effective as combination with cyclophosphamide (HR 0.62, p=0.04). 102 In a retrospective analysis from Japan, intravenous busulfan + cyclophosphamide had comparable outcomes with TBI-based regimens in ALL.…”