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血缘脐带血移植中,对于 40-60 岁急性髓系白血病患者,降低强度预处理与清髓性预处理的比较——代表欧洲血液与骨髓移植学会(EBMT)的细胞治疗和免疫生物学工作组(CTIWP)和 Eurocord。

Reduced-Intensity versus Myeloablative Conditioning in Cord Blood Transplantation for Acute Myeloid Leukemia (40-60 years) across Highly Mismatched HLA Barriers-On Behalf of Eurocord and the Cellular Therapy & Immunobiology Working Party (CTIWP) of EBMT.

机构信息

Clinical Research Division, Program in Immunology, Fred Hutchison Cancer Research Centre, Seattle, Washington.

Eurocord, Hopital Saint Louis-EA3518, Paris, France.

出版信息

Biol Blood Marrow Transplant. 2020 Nov;26(11):2098-2104. doi: 10.1016/j.bbmt.2020.07.025. Epub 2020 Jul 26.

Abstract

The use of myeloablative conditioning (MAC) in umbilical cord blood transplantation (UCBT) has been associated with high nonrelapse mortality (NRM) in patients aged >40 years, especially those having a high HLA disparity, thus limiting wider applications. We hypothesized that the NRM advantage of reduced-intensity conditioning (RIC) and higher graft-versus-leukemia effect associated with greater HLA disparities would expand its use for patients (aged 40 to 60 years) without compromising efficacy and compared outcomes between RIC and MAC regimens. In total, 288 patients aged 40 to 60 years, with de novo acute myeloid leukemia, receiving UCBT with at least 2 HLA mismatches with RIC (n = 166) or MAC (n = 122) regimens were included. As compared to RIC, the MAC cohort included relatively younger patients, having received more single UCBT, with lower total nucleated cell counts and more in vivo T cell depletion. Median time to neutrophil engraftment, infections (bacterial, viral, and fungal), and grade II to IV acute and chronic graft-versus-host disease were similar in both groups. In the multivariate analysis, overall survival (hazard ratio [HR], 0.98; P = .9), NRM (HR, 0.68; P = .2), and relapse (HR, 1.24; P = .5) were not different between RIC and MAC. Refractory disease was associated with worse survival. Outcomes of UBCT for patients aged 40 to 60 years having ≥2 HLA mismatches are comparable after the RIC or MAC regimen.

摘要

在脐带血移植(UCBT)中使用清髓性条件(MAC)与 40 岁以上患者的高非复发死亡率(NRM)相关,尤其是那些 HLA 差异较大的患者,因此限制了更广泛的应用。我们假设,与 HLA 差异较大相关的降低强度条件(RIC)和更高的移植物抗白血病效应的 NRM 优势将扩大其在年龄在 40 至 60 岁之间的患者中的应用,而不会影响疗效,并比较 RIC 和 MAC 方案之间的结果。共有 288 名年龄在 40 至 60 岁、患有初发性急性髓系白血病的患者接受了至少 2 个 HLA 错配的 UCBT,采用 RIC(n=166)或 MAC(n=122)方案。与 RIC 相比,MAC 队列包括相对较年轻的患者,接受了更多的单次 UCBT,总核细胞计数较低,体内 T 细胞耗竭更多。两组患者的中性粒细胞植入中位时间、感染(细菌、病毒和真菌)、Ⅱ级至Ⅳ级急性和慢性移植物抗宿主病的发生率相似。多变量分析显示,RIC 和 MAC 组的总生存率(风险比[HR],0.98;P=0.9)、NRM(HR,0.68;P=0.2)和复发(HR,1.24;P=0.5)无差异。难治性疾病与较差的生存相关。对于具有≥2 个 HLA 错配的年龄在 40 至 60 岁之间的患者,接受 RIC 或 MAC 方案后的 UCBT 结果是可比的。

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