Kids Cancer Centre, Sydney Children's Hospital, Randwick, New South Wales, Australia.
Australasian Bone Marrow Transplant Recipient Registry, Darlinghurst, New South Wales, Australia.
Biol Blood Marrow Transplant. 2020 Nov;26(11):2068-2074. doi: 10.1016/j.bbmt.2020.07.028. Epub 2020 Jul 28.
Total body irradiation (TBI)/cyclophosphamide (CY) is a standard-of-care conditioning regimen in allogeneic hematopoietic stem cell transplant (HSCT) for pediatric acute lymphoblastic leukemia (ALL). This study sought to identify whether the addition of thiotepa (TT) to TBI/CY improves HSCT outcomes for pediatric patients with ALL. A retrospective analysis was performed on 347 pediatric ALL patients who underwent HSCT between 1995 and 2015, with 242 receiving TBI/CY/TT and 105 patients receiving TBI/CY. There were no statistical differences in age, donor source, or complete remission status between the 2 groups. Comparison of the TBI/CY/TT versus TBI/CY groups demonstrated no difference in transplant-related mortality at 1 (11% versus 11%), 5 (13% versus 16%), or 10 years (16% versus 16%). There was lower relapse in the TBI/CY/TT group at 1 (14% versus 26%), 5 (24% versus 36%), 10 (26% versus 37%), and 15 years (26% versus 37%) (P= .02) but was not statistically significant on multivariate analysis. The TBI/CY/TT group showed a trend toward improved disease-free survival (DFS) at 5 (59% versus 47%), 10 (56% versus 46%), and 15 years (49% versus 40%) (P = .05) but was not statistically significant on multivariate analysis. Comparing overall survival at 5 (62% versus 53%), 10 (57% versus 50%), and 15 years (50% versus 44%) demonstrated no statistical difference between the 2 groups. The addition of thiotepa to TBI/CY demonstrated no increase in transplant-related mortality for pediatric ALL HSCT but was unable to demonstrate significant benefit in disease control. Minimal residual disease status remained the key risk factor impacting both relapse and DFS. More studies are warranted to better clarify the benefits of using thiotepa in conditioning for ALL HSCT.
全身照射(TBI)/环磷酰胺(CY)是异基因造血干细胞移植(HSCT)治疗儿科急性淋巴细胞白血病(ALL)的标准治疗方案。本研究旨在确定在 TBI/CY 中加入噻替哌(TT)是否能改善儿科 ALL 患者 HSCT 的结果。对 1995 年至 2015 年间接受 HSCT 的 347 例儿科 ALL 患者进行了回顾性分析,其中 242 例接受 TBI/CY/TT,105 例接受 TBI/CY。两组在年龄、供者来源或完全缓解状态方面无统计学差异。TBI/CY/TT 组与 TBI/CY 组比较,1 年(11%比 11%)、5 年(13%比 16%)和 10 年(16%比 16%)的移植相关死亡率无差异。TBI/CY/TT 组 1 年(14%比 26%)、5 年(24%比 36%)、10 年(26%比 37%)和 15 年(26%比 37%)的复发率较低(P=0.02),但多变量分析无统计学意义。TBI/CY/TT 组在 5 年(59%比 47%)、10 年(56%比 46%)和 15 年(49%比 40%)的无病生存(DFS)方面有改善趋势(P=0.05),但多变量分析无统计学意义。两组在 5 年(62%比 53%)、10 年(57%比 50%)和 15 年(50%比 44%)的总生存比较无统计学差异。TBI/CY 中加入噻替哌并未增加儿科 ALL HSCT 的移植相关死亡率,但未能证明在疾病控制方面有显著获益。微小残留病状态仍然是影响复发和 DFS 的关键危险因素。需要更多的研究来更好地阐明噻替哌在 ALL HSCT 中的应用的益处。