T-cell receptor αβ+ and CD19+ cell-depleted haploidentical and mismatched hematopoietic stem cell transplantation in primary immune deficiency
T-cell receptor αβ+ and CD19+ cell-depleted haploidentical and mismatched hematopoietic stem cell transplantation in primary immune deficiency
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DOI：
10.1016/j.jaci.2017.07.008
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发表时间：
2018-04-01
影响因子：
14.2
通讯作者：
Slatter, Mary
中科院分区：
文献类型：
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作者：
Shah, Ravi M.;Elfeky, Reem;Slatter, Mary
背景：异基因造血干细胞移植（HSCT）被用作原发性免疫缺陷（PID）的治疗方法。最好的结果是用HLA匹配的供体实现的，但是当匹配的供体不可用时，单倍相合或不匹配的无关供体（mMUD）可能是有用的。各种策略被用来减轻移植物抗宿主病（GvHD）和与这种transplants.Objective相关的排斥反应的风险：我们试图评估从移植物中耗尽引起GvHD的T细胞受体（TCR）α β CD 3（+）细胞后的单倍体相合或mMUD HSCT的结果。在条件性（3例除外）PID患儿中给予去除CD 3（+）TCR α β（+）/CD 19（+）的移植物。Treosulfan（白消安1例），氟达拉滨，噻替派，抗胸腺细胞球蛋白或阿仑单抗调理中使用的77%的情况下，和所有，但4接受GvHD prophylaxies.Results：25例患者12种类型的PID收到26 HSCT。三个人接受了移植难治性GvHD后发展的第一个脐带移植。中位随访时间为20.8个月（范围：5个月至3.3年），25例患者中有21例存活并治愈了基础免疫缺陷。3年总生存率和无事件生存率分别为83.9%和80.4%。II至IV级急性GvHD的累积发生率为22% +/-8.7%。未观察到内脏或慢性GvHD病例。1年时移植失败、巨细胞病毒和/或腺病毒感染的累积发生率和移植相关死亡率分别为4.2% +/-4.1%、58.8% +/-9.8%和16.1% +/-7.4%。结论：去除CD 3（+）TCR α β（+）和CD 19（+）细胞的单倍体相合HSCT或mMUD HSCT是一种可行的治疗方案。
Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is used as a therapeutic approach for primary immunodeficiencies (PIDs). The best outcomes have been achieved with HLA-matched donors, but when a matched donor is not available, a haploidentical or mismatched unrelated donor (mMUD) can be useful. Various strategies are used to mitigate the risk of graft-versus-host disease (GvHD) and rejection associated with such transplants.Objective: We sought to evaluate the outcomes of haploidentical or mMUD HSCT after depleting GvHD-causing T-cell receptor (TCR) alpha beta CD3(+) cells from the graft.Methods: CD3(+)TCR alpha beta(+)/CD19(+) depleted grafts were given in conditioned (except 3) children with PIDs. Treosulfan (busulfan in 1 patient), fludarabine, thiotepa, and anti-thymocyte globulin or alemtuzumab conditioning were used in 77% of cases, and all but 4 received GvHD prophylaxis.Results: Twenty-five patients with 12 types of PIDs received 26 HSCTs. Three underwent transplantation for refractory GvHD that developed after the first cord transplantation. At a median follow-up of 20.8 months (range, 5 month-3.3 years), 21 of 25 patients survived and were cured of underlying immunodeficiency. Overall and event-free survival at 3 years were 83.9% and 80.4%, respectively. Cumulative incidence of grade II to IV acute GvHD was 22% +/- 8.7%. No case of visceral or chronic GvHD was seen. Cumulative incidences of graft failure, cytomegalovirus, and/or adenoviral infections and transplant-related mortality at 1 year were 4.2% +/- 4.1%, 58.8% +/- 9.8%, and 16.1% +/- 7.4%, respectively. Patients undergoing transplantation with systemic viral infections had poor survival in comparison with those with absent or resolved infections (33.3% vs 100%).Conclusion: CD3(+)TCR alpha beta(+) and CD19(+) cell-depleted haploidentical or mMUD HSCT is a practical and viable alternative for children with a range of PIDs.