Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Biol Blood Marrow Transplant. 2011 Oct;17(10):1460-71. doi: 10.1016/j.bbmt.2011.02.001. Epub 2011 Mar 1.
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.
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。