Impact of total body irradiation on successful neutrophil engraftment in unrelated bone marrow or cord blood transplantation

Abstract

Total body irradiation (TBI) has been thought to promote donor cell engraftment in allogeneic hematopoietic cell transplantation (HCT) from alternative donors. However, recent progress in HCT strategies may affect the clinical significance of TBI on neutrophil engraftment. With the use of a Japanese transplant registry database, we analyzed 3933 adult recipients (>15 y.o.) who underwent HCT between 2006 and 2013 from an 8/8 HLA-matched unrelated bone marrow donor (MUD, n = 1367), an HLA-mismatched unrelated bone marrow donor (MMUD, n = 1102), or unrelated cord blood (CBT, n = 1464). Conditioning regimens were divided into five groups: High-TBI-(>8Gy), Low-TBI- (≤8Gy), and no-TBI-myeloablative conditioning (MAC), and Low-TBI- and no-TBI-reduced-intensity conditioning (RIC). In both MUD and MMUD, neutrophil engraftment rate was >90% in each of the five conditioning groups, and TBI was not associated with prompt neutrophil engraftment in multivariate analyses. Conversely, in CBT, TBI regimens had a higher rate of day-30 neutrophil engraftment than no-TBI-regimens: 78% in High-TBI-MAC, 83% in Low-TBI-MAC, and 76% in Low-TBI-RIC versus 65% in No-TBI-MAC, and 68% in No-TBI-RIC (P < .001). Multivariate analyses in CBT demonstrated that TBI-regimens were significantly associated with a higher rate of neutrophil engraftment. Subsequently focusing on CBT patients alone, TBI-regimens were significantly associated with a higher rate of neutrophil engraftment in patients who received CBT with a 4/6 or less HLA allele-match, or who had anti-HLA antibodies. In summary, TBI-regimens had no impact on neutrophil engraftment in the current practice of unrelated bone marrow transplantation. However, in CBT, TBI is still necessary to enhance engraftment.

Better outcomes of modified myeloablative conditioning without antithymocyte globulin versus myeloablative conditioning in cord blood transplantation for hematological malignancies: A retrospective (development) and a prospective (validation) study

“…Similar to our results, some authors have reported that lower conditioning intensity is associated with delayed immune reconstitution and a higher incidence of GF 8, 9. Notably, conditioning type (TBI‐based or Bu‐based) was significantly different between the MAC group and MMAC group in the retrospective study, and TBI has always been a favorable factor in improving neutrophil engraftment in CBT 22, 23. To identify the relationship between conditioning type and neutrophil engraftment rate in this study, we did a univariate analysis, and there was no statistical difference ( p  = 0.77).…”

A prospective multicenter phase II study of intrabone marrow transplantation of unwashed cord blood using reduced‐intensity conditioning

“…In recent large‐scale studies of IV‐CBT using reduced‐intensity conditioning (RIC) with low‐dose total body irradiation (TBI), the full donor engraftment rate after transplantation was 65%‐83%, and the median time to neutrophil recovery (>0.5 × 10 9 /L) was 20‐21 days. On the other hand, the recovery of platelets varies from 40% to 70% at 100 days, and the median time to platelet recovery (>20 × 10 9 /L) ranges from 50 to 100 days .…”

“…The reason why our patients achieved a neutrophil recovery 5‐6 days faster remains to be determined, but the use of RIC and/or unwashed CB that we used may have contributed to faster donor engraftment. Regarding the effects of the intensity of conditioning treatment on neutrophil recovery after IV‐CBT, in the analysis of data from the Transplant Registry Unified Management Program system in Japan, which is the largest registry of the outcomes of Japanese transplant patients, the median time to neutrophil engraftment was better with low‐dose TBI‐RIC (21 days) than with high‐dose TBI‐MAC (23 days), although the difference was not significant …”

“…The expected proportion was based on the outcomes of an IBM-CBT study conducted by Frassoni et al, 16 who reported that the donor engraftment proportion was 81.0%, and the outcomes of IV-CBT studies, in which the donor engraftment proportion was reported as 65%-83%. [25][26][27] Continuous and categorical data are presented as medians with ranges (minimums-maximums) and as frequencies with percentages, respectively. The primary endpoint was analyzed with the use of a one-sided exact binomial test, being consistent with the sample size calculation method.…”

“…Assuming a dropout rate of about 10%, a total of 40 patients were required. The expected proportion was based on the outcomes of an IBM‐CBT study conducted by Frassoni et al, who reported that the donor engraftment proportion was 81.0%, and the outcomes of IV‐CBT studies, in which the donor engraftment proportion was reported as 65%‐83% …”