Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.
Am J Hematol. 2017 Feb;92(2):171-178. doi: 10.1002/ajh.24613.
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.
全身照射(TBI)曾被认为可促进异基因造血细胞移植(HCT)中来自替代供体的供体细胞植入。然而,HCT 策略的最新进展可能会影响 TBI 对中性粒细胞植入的临床意义。利用日本移植登记数据库,我们分析了 2006 年至 2013 年间 3933 例接受 HCT 的成年患者(>15 岁),这些患者来自 8/8 HLA 匹配的无关供体骨髓(MUD,n=1367)、HLA 不匹配的无关供体骨髓(MMUD,n=1102)或无关脐带血(CBT,n=1464)。预处理方案分为五组:高 TBI(>8Gy)、低 TBI(≤8Gy)和无 TBI-清髓性预处理(MAC)以及低 TBI-和无 TBI-减轻强度预处理(RIC)。在 MUD 和 MMUD 中,五种预处理方案中的每一种方案的中性粒细胞植入率均>90%,并且在多变量分析中 TBI 与迅速中性粒细胞植入无关。相反,在 CBT 中,TBI 方案比无 TBI 方案的第 30 天中性粒细胞植入率更高:高 TBI-MAC 组为 78%,低 TBI-MAC 组为 83%,低 TBI-RIC 组为 76%,无 TBI-MAC 组为 65%,无 TBI-RIC 组为 68%(P<.001)。CBT 的多变量分析表明,TBI 方案与更高的中性粒细胞植入率显著相关。随后,仅关注 CBT 患者,TBI 方案与 HLA 等位基因匹配为 4/6 或更少或具有抗 HLA 抗体的 CBT 患者的更高中性粒细胞植入率显著相关。总之,在当前无关骨髓移植的实践中,TBI 方案对中性粒细胞植入没有影响。然而,在 CBT 中,仍需要 TBI 来增强植入。