CD3/CD19去除t细胞减少的异体移植:大部分是有效的,但不是稳健的。

Clinical Hematology International Pub Date : 2021-08-02 eCollection Date: 2021-09-01 DOI:10.2991/chi.k.210725.001
Eliza Wiercinska, Erhard Seifried, Halvard Bonig
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引用次数: 3

摘要

侵袭性t细胞耗竭,体外或体内,是单倍体干细胞移植存活的先决条件。经典的t细胞耗尽移植,免疫磁富集CD34+细胞,在移植物抗宿主反应性方面是非常安全的,但与移植相关和复发死亡率非常高,总体生存率仅为20%。因此,开发了T细胞和b细胞消耗方案,理由是移植大部分自然杀伤(NK)细胞和大量残留T细胞可能提高生存率,这在原则上得到了证实。经常不能达到充分的t细胞耗竭的轶事报告促使我们中心对移植质量的总体数据进行审查。第一个观察结果是,随着PTCy方案取得进展,CD3/CD19联合消耗过程相对较少,8年内有13次消耗。T细胞和b细胞log-depletion的中位数分别为-3.89和-1.92;相反,CD34+细胞回收率普遍较高(中位数为92%),nk细胞回收率也较高(中位数为52%)。然而,该过程未能在13种制剂中的两种中产生令人满意的T细胞和b细胞消耗,其中一种产品可以通过第二轮消耗来挽救,代价是CD34+细胞的恢复。因此,在我们的研究中,这一过程对于常规临床应用来说不够稳健。假设其他中心也有类似的观察结果,这可能解释了其他方案的实施,如TCRαβ/CD19去除或未经处理的移植物移植,随后在体内去除。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

CD3/CD19 Depletion for T-cell Reduction of Allogeneic Transplants: Mostly Efficient, but not Robust.

CD3/CD19 Depletion for T-cell Reduction of Allogeneic Transplants: Mostly Efficient, but not Robust.

Aggressive T-cell depletion, in vitro or in vivo, is a prerequisite for survival of haplo-identical stem cell transplantation. The classical T-cell-depleted transplant, immunomagnetically enriched CD34+ cells, is very safe with respect to graft-versus-host reactivity, but associated with very high transplant-related and relapse mortality with an overall probability of survival of only 20%. Protocols for T- and B-cell depletion were therefore developed, reasoning that transplantation of the majority of Natural Killer (NK) cells and the substantial dose of residual T-cells might improve survival, which was, in principle, confirmed. Anecdotal reports of frequent failure to achieve adequate T-cell depletion prompted review of the aggregate data for transplant quality at our center. The first observation is the relative paucity of combined CD3/CD19 depletion processes as PTCy protocols have made inroads, 13 depletions in 8 years. Median T- and B-cell log-depletion were -3.89 and -1.92, respectively; instead of, CD34+ cell recovery was generally high (median 92%), as was NK-cell recovery (median 52%). However, the process failed to yield satisfactory T- and B-cell depletion in two out of 13 preparations, of which one product could be rescued by a second round of depletion, at the expense of CD34+ cell recovery. In our hands, the process is thus insufficiently robust for routine clinical use. Assuming similar observations in other centers, this may explain implementation of alternative protocols, such as TCRαβ/CD19 depletion or transplantation of unmanipulated grafts with subsequent in vivo depletion.

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