Impact of Low-Dose TBI on Outcome of Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation from HLA Identical Sibling for Acute Myeloid Leukemia

Abstract

▪IntroductionIn recent year, reduced-intensity conditioning (RIC) is increasingly used in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia (AML) patients considered unfit for myeloablative conditioning. Several RIC regimens include low-dose total body irradiation (TBI). However, it is unknown whether addition of low-dose TBI to RIC is beneficial. Therefore, we conducted retrospective analysis to elucidate the clinical impact of low-dose TBI in RIC on outcome of allo-HSCT from HLA identical sibling for AML patients.Patients and methodsClinical data of patients with AML aged over 15 years, who received RIC and underwent allo-HSCT from HLA identical sibling for the first time between January 2000 and December 2012, were extracted from the database the Japan Society for Hematopoietic Cell Transplantation. Low-dose TBI was defined as 2-4Gy of TBI. Overall survival (OS), relapse, Non relapse mortality (NRM) and engraftment were compared between patients who received low-dose TBI (TBI group) and patients who did not receive TBI (Non-TBI group) using log-rank test and Gray’s test respectively. To evaluate the association of patient characteristics with low-dose TBI, Cox proportional hazards model and Fine and Gray proportional hazards model were used for multivariate analyses.ResultsThere were 409 patients with AML who received RIC and underwent allo-HSCT from HLA identical sibling. Of those, 108 patients were TBI group and 301 patients were Non-TBI group. In term of graft source, a higher proportion of TBI group received bone marrow (BM) than non-TBI group (54.6% vs. 31.2% [P<0.001]). Age, gender, disease status, performance status (PS), cytogenetic risk category were comparable between both groups. The probability of 5-years OS (36.0% vs. 32.8% [P=0.656]), relapse (37.3% vs. 38.8% [P=0.933]), and NRM (23.9% vs. 25.2% P=[0.686]) were comparable between both groups. Although, the median time to engraftment of neutrophil and platelet were shorter in non-TBI group in whole patients (17d vs. 15d [P=0.031], 22.5d vs. 19d [P=0.024]), subgroup analysis according to donor source showed the median time to engraftment of neutrophil and platelet were similar between both groups in BM recipients (17d vs. 16.5d [P=0.395], 25.0d vs. 23.5d [P=0.392]) and peripheral blood recipients (14d vs. 15d [P=0.213], 20d vs. 17d [P=0.174]). In multivariate analysis, low-dose TBI was not associated with OS, relapse, NRM, and engraftment after adjusting graft source, age, gender, disease status, PS, and cytogenetic risk category.ConclusionThis study showed that adding low-dose TBI to RIC did not affect clinical outcome of allo-HSCT from HLA identical sibling for AML patients. These results suggested RIC regimen without low-dose TBI is valid option for older or medically infirm AML patients who receive allo-HSCT from HLA identical sibling. DisclosuresNo relevant conflicts of interest to declare.