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以噻替派为基础的预处理方案与全身照射作为异基因造血干细胞移植治疗急性淋巴细胞白血病的清髓性预处理方案的比较:来自欧洲血液和骨髓移植学会急性白血病工作组的匹配对分析。

Thiotepa-based conditioning versus total body irradiation as myeloablative conditioning prior to allogeneic stem cell transplantation for acute lymphoblastic leukemia: A matched-pair analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

机构信息

EBMT Office Paris, Hôpital Saint-Antoine, Paris, France.

Hematology Division, Chaim Sheba Medical Center, Tel Aviv University, Tel-Hashomer, Israel.

出版信息

Am J Hematol. 2017 Oct;92(10):997-1003. doi: 10.1002/ajh.24823. Epub 2017 Jul 19.

Abstract

The optimal conditioning regimen to employ before hematopoietic stem cell transplantation in acute lymphoblastic leukemia (ALL) is still undecided, and while cyclophosphamide/total body irradiation (Cy/TBI) is the most commonly used myeloablative regimen, there are concerns regarding long-term toxicity for patients conditioned with this regimen. Thiotepa-based conditioning is an emerging radiation-free regimen with recent publications indicative of comparable clinical outcomes to TBI-based conditioning. In this analysis of the acute leukemia working party of the EBMT, we performed a retrospective matched-pair analysis, evaluating the outcome of adult patients with ALL who received thiotepa-based conditioning (n = 180) with those receiving Cy/TBI conditioning (n = 540). The 2-year leukemia-free survival and overall survival (OS) rates of both conditioning regimens were comparable, 33% for thiotepa [95% confidence interval (CI): 26.4-42.8] versus 39% for Cy/TBI (95% CI: 34.8-44.5] (P = .33) and 46.5% [95% CI: 38.6-56.1] versus 48.8% [95% CI: 44.2-54] (P = .9), respectively. There was no significant difference between the two regimens in the incidence of either acute graft versus host disease (GVHD) or chronic GVHD. Multivariate analysis demonstrated increased relapse incidence for thiotepa conditioning compared to Cy/TBI (HR = 1.78, 95% CI, 1.07-2.95; P = .03) which did not affect OS. Our results indicate that thiotepa-based conditioning may not be inferior to Cy/TBI for adult patients with ALL.

摘要

在急性淋巴细胞白血病(ALL)患者进行造血干细胞移植前,采用何种最佳预处理方案仍未确定。环磷酰胺/全身照射(Cy/TBI)是最常用的清髓性预处理方案,但该方案存在长期毒性问题。以噻替哌为基础的预处理方案是一种新兴的无辐射预处理方案,最近的研究表明,其临床疗效与 TBI 预处理方案相当。在这项 EBMT 急性白血病工作组的分析中,我们进行了回顾性配对分析,评估了接受噻替哌预处理(n=180)和接受 Cy/TBI 预处理(n=540)的 ALL 成年患者的结果。两种预处理方案的 2 年无白血病生存率和总生存率(OS)相当,噻替哌组为 33%(95%置信区间[CI]:26.4-42.8),Cy/TBI 组为 39%(95% CI:34.8-44.5)(P=0.33),分别为 46.5%(95% CI:38.6-56.1)和 48.8%(95% CI:44.2-54.0)(P=0.9)。两种方案在急性移植物抗宿主病(GVHD)或慢性 GVHD 的发生率方面没有显著差异。多变量分析显示,与 Cy/TBI 相比,噻替哌预处理的复发率更高(HR=1.78,95% CI,1.07-2.95;P=0.03),但这并不影响 OS。我们的结果表明,对于 ALL 成年患者,噻替哌预处理方案可能并不逊于 Cy/TBI。

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