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双份脐血移植后不使用抗胸腺细胞球蛋白的严重感染风险和免疫恢复。

Serious infection risk and immune recovery after double-unit cord blood transplantation without antithymocyte globulin.

机构信息

Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.

出版信息

Biol Blood Marrow Transplant. 2011 Oct;17(10):1460-71. doi: 10.1016/j.bbmt.2011.02.001. Epub 2011 Mar 1.

Abstract

Factors contributing to infection risk after cord blood transplantation (CBT) include the use of anti-thymocyte globulin (ATG), prolonged neutropenia, and failure to transfer immunity. In the present study, we investigated the potential of double-unit CBT without ATG to reduce the risk of infection and evaluated the nature of serious infections in the first year after CBT using this approach. Seventy-two predominantly adult patients underwent CBT for hematologic malignancies; of these, 52 patients received myeloablative conditioning, and 20 received nonmyeloablative conditioning. The peak incidences of bacterial infections (32%), fungal infections (14%), and bacterial/fungal pneumonias (10%) occurred in the first 30 days posttransplantation. Three such infections contributed to early mortality. The peak incidence of viral infections was 31-60 days posttransplantation, affecting 30% of patients. Cytomegalovirus (CMV) was the most common viral infection. CMV infections occurring before day 120 (n = 23) had no relationship with graft-versus-host disease (GVHD), whereas CMV infections occurring after day 120 (n = 5), along with all cases of Epstein-Barr virus viremia (n = 5) and adenoviral enteritis (n = 2), occurred exclusively in the context of GVHD therapy or corticosteroid use for another indication. Viral infections had the highest lethality: 2 were a direct cause of death, and 3 contributed to death. Patients exhibited steady immune recovery, achieving a median CD3(+)4(+) T cell count >200 cells/μL by day 120 post-CBT, and no infection-related deaths occurred after day 120. Our results suggest that double-unit CBT without ATG is associated with prompt T cell recovery, and, unlike in CBT incorporating ATG, infection is rarely a primary cause of death. However, CBT without ATG is associated with a significant risk of GVHD, and serious infections remain a challenge, especially in the setting of GVHD. New strategies are needed to further reduce infectious complications after CBT; these will require earlier neutrophil recovery and more effective prevention of GVHD, ideally without the profound T cell depletion associated with ATG therapy.

摘要

导致脐血移植(CBT)后感染风险的因素包括使用抗胸腺细胞球蛋白(ATG)、中性粒细胞减少时间延长和免疫转移失败。在本研究中,我们研究了不使用 ATG 的双单位 CBT 降低感染风险的潜力,并使用这种方法评估了 CBT 后第一年严重感染的性质。72 例主要为成人的血液系统恶性肿瘤患者接受 CBT;其中 52 例患者接受了清髓性预处理,20 例患者接受了非清髓性预处理。细菌感染(32%)、真菌感染(14%)和细菌/真菌感染性肺炎(10%)的发生率峰值出现在移植后 30 天内。有 3 例此类感染导致早期死亡。病毒感染的发生率峰值为移植后 31-60 天,影响 30%的患者。巨细胞病毒(CMV)是最常见的病毒感染。发生在 120 天之前的 CMV 感染(n=23)与移植物抗宿主病(GVHD)无关,而发生在 120 天之后的 CMV 感染(n=5)以及所有 EBV 血症(n=5)和腺病毒肠炎(n=2)均仅发生在 GVHD 治疗或因其他原因使用皮质类固醇的情况下。病毒感染的致死率最高:2 例是直接死亡原因,3 例导致死亡。患者表现出稳定的免疫恢复,在 CBT 后 120 天达到中位数 CD3(+)4(+)T 细胞计数>200 个/μL,并且在 120 天之后没有因感染相关死亡。我们的结果表明,不使用 ATG 的双单位 CBT 与迅速的 T 细胞恢复有关,与包含 ATG 的 CBT 不同,感染很少成为死亡的主要原因。然而,不使用 ATG 的 CBT 与 GVHD 的显著风险相关,严重感染仍然是一个挑战,尤其是在 GVHD 的情况下。需要新的策略来进一步降低 CBT 后的感染并发症;这些策略将需要更早的中性粒细胞恢复和更有效的 GVHD 预防,理想情况下不需要与 ATG 治疗相关的严重 T 细胞耗竭。

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