General and Virus-Specific Immune Cell Reconstitution after Double Cord Blood Transplantation.

General and Virus-Specific Immune Cell Reconstitution after Double Cord Blood Transplantation.
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DOI:
10.1016/j.bbmt.2015.02.017
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发表时间:
2015-07
期刊:
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
影响因子:
--
通讯作者:
Shpall EJ
Shpall EJ
中科院分区:
其他
文献类型:
--
作者:
Saliba RM;Rezvani K;Leen A;Jorgensen J;Shah N;Hosing C;Parmar S;Oran B;Olson A;Rondon G;Chen J;Martinez C;Hamdi A;Mehta RS;Chemaly RF;Saunders IM;Bollard CM;Shpall EJ

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脐带血移植(CBT)对许多血液恶性肿瘤患者具有治愈性,但与人类白细胞抗原(HLA)匹配的骨髓或外周血祖细胞移植相比,其与延迟的免疫恢复和增加的病毒感染风险相关。在这项研究中,我们评估了125例连续的恶性血液病患者淋巴细胞恢复的意义,这些患者在我们的机构接受了含抗胸腺细胞球蛋白方案的双单位CBT(DUCBT)。前瞻性评估了65例患者的T、自然杀伤(NK)和B细胞恢复情况,并在46例患者中检查了针对腺病毒、EB病毒、巨细胞病毒、BK病毒、呼吸道合胞病毒和流感抗原的病毒特异性T细胞恢复情况。我们的研究结果表明,在DUCBT的接受者中,第30天的绝对淋巴细胞计数高度预测非复发死亡率(NRM)和总生存率(OS)。DUCBT后免疫恢复的特征是与B和NK细胞优先扩增相关的长期CD 8+和CD 4 + T淋巴细胞减少。我们还观察到CBT后第一年病毒特异性CD4+和CD8 + T细胞应答的定量和功能恢复严重延迟。总之,我们的数据支持旨在优化病毒特异性T细胞恢复以改善CBT后结果的努力。
Cord blood transplantation (CBT) is curative for many patients with hematologic malignancies but is associated with delayed immune recovery and an increased risk of viral infections compared to human leukocyte antigen (HLA) matched bone marrow or peripheral blood progenitor cell transplantation. In this study we evaluated the significance of lymphocyte recovery in 125 consecutive patients with hematologic malignancies who underwent double-unit CBT (DUCBT) with an anti-thymocyte globulin-containing regimen at our institution. A subset of 65 patients were prospectively evaluated for recovery of T, natural killer (NK) and B cells and in 46 patients we also examined viral-specific T cell recovery against Adenovirus, Epstein-Barr virus, cytomegalovirus, BK virus, respiratory syncytial virus and Influenza antigen. Our results indicate that in recipients of DUCBT, the day 30 absolute lymphocyte count is highly predictive of non-relapse mortality (NRM) and overall survival (OS). Immune recovery post-DUCBT was characterized by prolonged CD8+ and CD4+ T lymphopenia associated with preferential expansion of B and NK cells. We also observed profound delays in quantitative and functional recovery of viral-specific CD4+ and CD8+ T-cell responses for the first year post-CBT. Taken together, our data support efforts aimed at optimizing viral-specific T cell recovery to improve outcomes post-CBT.