Clinical significance of low-dose total body irradiation in HLA-mismatched reduced-intensity stem cell transplantation

Abstract

The significance of low-dose total body irradiation (TBI) in HLA-mismatched reduced-intensity conditioning stem cell transplantation (RICT) remains unknown. We, retrospectively, evaluated the impact of low-dose TBI in patients with hematological malignancies who received first RICT from ≥1 antigen-mismatched donors between 2004 and 2014. Of the 575 patients, 361 patients received low-dose TBI (2 or 4 Gy). There were no significant differences in neutrophil engraftment or platelet recovery between TBI and non-TBI groups. The benefit of low-dose TBI on neutrophil engraftment was not observed in any subgroups. Low-dose TBI was not associated with decreased secondary graft failure. Suppressed mixed chimerism and autologous hematopoiesis by low-dose TBI was observed. There were no significant differences in cumulative incidences of acute GVHD or nonrelapse mortality rates in either group; however, low-dose TBI improved overall survival (OS), especially in patients with high-risk disease, multi-HLA mismatch, and fludarabine/busulfan conditioning. Multivariate analysis demonstrated that low-dose TBI was an independent prognostic factor for OS. Compared with the non-TBI group, 4 Gy TBI, but not 2 Gy TBI, was associated with increased acute GVHD and reduced relapse. These findings suggest that low-dose TBI may be beneficial for patients at high risk for relapse in HLA-mismatched RICT.

Sirolimus with CSP and MMF as GVHD prophylaxis for allogeneic transplantation with HLA antigen–mismatched donors

“…Outcomes after HLA-mismatched donor HCT in the context of reduced-intensity conditioning have mainly been addressed in registry-based studies [14][15][16] ; observed ranges of grade 2 to 4 acute and chronic GVHD were similar to the current trial, but the incidence of grade 3 to 4 acute GVHD was higher, ranging from 13% to 27%, and resulting in NRM between 31.9% and 39% and overall survival rates between 30% and 48% at 3 years' posttransplantation. Parody et al 17 investigated the efficacy of sirolimus in combination with tacrolimus after reduced-intensity HCT in a prospective study in which a subpopulation of patients (n 5 20) was mismatched for a single HLA antigen.…”

The impacts of total body irradiation on umbilical cord blood hematopoietic stem cell transplantation

“…40 However, a study of the clinical significance of low-dose TBI in patients with hematologic malignancies undergoing HSCT found that low-dose TBI improved OS in patients with a high-risk disease and multi-HLA mismatch in comparing to Flu/Bu conditioning. 41 It seems that TBI dosage could play a crucial role in post-transplant outcomes. On the other side, it is well accepted that low-dose TBI is less toxic.…”