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单倍型相合造血干细胞移植治疗血液系统恶性肿瘤:一种新型预处理方案,使用抗T淋巴细胞免疫球蛋白替代抗胸腺细胞球蛋白进行体内T细胞清除。

Haploidentical hematopoietic stem cell transplantation for hematologic malignancies: a novel conditioning regimen with anti-T lymphocyte immunoglobulin instead of anti-thymocyte globulin for in vivo T cell depletion.

作者信息

Huang Xiao-Bing, Yang Xi, Li Cheng-Long, Zhang Rong, Wang Wen, Huang Jia-Wen, Ye Xue-Mei, Wang Yu, Mao Yan, Pu Wen-Qi, Zhou Yang

机构信息

Department of Hematology, Sichuan Provincial People's Hospital, Affiliated Hospital of University of Electronic Science and Technology of China, Chengdu, China.

Sichuan Provincial Clinical Research Center for Hematologic Disease, Chengdu, China.

出版信息

Bone Marrow Transplant. 2025 Jan;60(1):39-46. doi: 10.1038/s41409-024-02433-w. Epub 2024 Oct 14.

Abstract

We evaluated the safety and efficacy of a novel protocol for haploidentical stem cell transplantation (haplo-SCT) in 312 patients with hematologic malignancies. The protocol evolved from the Beijing platform replacing ATG with ATLG; adding Fludarabine and removing cytarabine and Simustine. GVHD prophylaxis combined Basiliximab and low-dose cyclophosphamide post-transplant; overall, the conditioning duration was shortened. Median times to neutrophil and platelet recovery were both 11 days. Graft rejection occurred in 0.96% of patients. Cumulative incidences of grades II-IV and III-IV acute GVHD by day 200 were 35.3% and 8.9%, respectively. Probabilities of total and extensive chronic GVHD at 2 years were 40.7% and 14.7%. CMV viremia was observed in 35.6% of patients, with a 1.9% 100-day CMV pneumonia incidence and no CMV-related mortality. Cumulative incidences of non-relapse mortality at 100 days, 1 year, and 2 years were 2.9, 4.4, and 6.6%. The 4-year OS, RFS, and GRFS rates were 78.9, 70.7, and 47.3%. Older recipient age was associated with higher NRM, while positive pre-transplant MRD predicted worse OS, RFS, and higher relapse incidence. Our novel protocol for haplo-SCT is associated with low infection rates and acceptable risks of graft failure, severe GVHD, and mortality, representing a safe and effective haploidentical transplantation strategy.

摘要

我们评估了一种新型单倍体相合干细胞移植(haplo-SCT)方案在312例血液系统恶性肿瘤患者中的安全性和有效性。该方案源自北京方案,用ATLG替代ATG;添加氟达拉滨并去除阿糖胞苷和司莫司汀。移植物抗宿主病(GVHD)预防采用巴利昔单抗联合移植后低剂量环磷酰胺;总体而言,预处理时间缩短。中性粒细胞和血小板恢复的中位时间均为11天。0.96%的患者发生移植物排斥反应。至第200天,II-IV级和III-IV级急性GVHD的累积发生率分别为35.3%和8.9%。2年时全面慢性GVHD和广泛慢性GVHD的概率分别为40.7%和14.7%。35.6%的患者观察到巨细胞病毒(CMV)血症,100天CMV肺炎发病率为1.9%,且无CMV相关死亡。100天、1年和2年时非复发死亡率的累积发生率分别为2.9%、4.4%和6.6%。4年总生存(OS)率、无复发生存(RFS)率和粒细胞恢复无病生存(GRFS)率分别为78.9%、70.7%和47.3%。受者年龄较大与较高的非复发死亡率相关,而移植前微小残留病(MRD)阳性预示着较差的OS、RFS和较高的复发率。我们的新型haplo-SCT方案感染率低,移植物失败、严重GVHD和死亡风险可接受,是一种安全有效的单倍体相合移植策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b889/11726451/bcc498590629/41409_2024_2433_Fig1_HTML.jpg

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