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单倍体相合移植后人类疱疹病毒6型感染:免疫恢复与结局

Human Herpesvirus 6 Infection Following Haploidentical Transplantation: Immune Recovery and Outcome.

作者信息

Greco Raffaella, Crucitti Lara, Noviello Maddalena, Racca Sara, Mannina Daniele, Forcina Alessandra, Lorentino Francesca, Valtolina Veronica, Rolla Serena, Dvir Roee, Morelli Mara, Giglio Fabio, Barbanti Maria Chiara, Lupo Stanghellini Maria Teresa, Oltolini Chiara, Vago Luca, Scarpellini Paolo, Assanelli Andrea, Carrabba Matteo G, Marktel Sarah, Bernardi Massimo, Corti Consuelo, Clementi Massimo, Peccatori Jacopo, Bonini Chiara, Ciceri Fabio

机构信息

Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy.

University of Milan, Milan, Italy.

出版信息

Biol Blood Marrow Transplant. 2016 Dec;22(12):2250-2255. doi: 10.1016/j.bbmt.2016.09.018. Epub 2016 Sep 30.

Abstract

Human herpesvirus 6 (HHV-6) is increasingly recognized as a potentially life-threatening pathogen in allogeneic hematopoietic stem cell transplantation (alloSCT). We retrospectively evaluated 54 adult patients who developed positivity to HHV-6 after alloSCT. The median time from alloSCT to HHV-6 reactivation was 34 days. HHV-6 was present in plasma samples from 31 patients, in bone marrow (BM) of 9 patients, in bronchoalveolar lavage fluid and liver or gut biopsy specimens from 33 patients, and in cerebrospinal fluid of 7 patients. Twenty-nine patients developed acute graft-versus-host disease (GVHD), mainly grade III-IV, and 15 had concomitant cytomegalovirus reactivation. The median absolute CD3 lymphocyte count was 207 cells/µL. We reported the following clinical manifestations: fever in 43 patients, skin rash in 22, hepatitis in 19, diarrhea in 24, encephalitis in 10, BM suppression in 18, and delayed engraftment in 11. Antiviral pharmacologic treatment was administered to 37 patients; nonetheless, the mortality rate was relatively high in this population (overall survival [OS] at 1 year, 38% ± 7%). A better OS was significantly associated with a CD3 cell count ≥200/µL at the time of HHV-6 reactivation (P = .0002). OS was also positively affected by the absence of acute GVHD grade III-IV (P = .03) and by complete disease remission (P = .03), but was not significantly influenced by steroid administration, time after alloSCT, type of antiviral prophylaxis, plasma viral load, or organ involvement. Although HHV-6 detection typically occurred early after alloSCT, better T cell immune reconstitution seems to have the potential to improve clinical outcomes. Our findings provide new insight into the interplay between HHV-6 and the transplanted immune system.

摘要

人类疱疹病毒6型(HHV-6)在异基因造血干细胞移植(alloSCT)中越来越被认为是一种潜在的危及生命的病原体。我们回顾性评估了54例alloSCT后HHV-6检测呈阳性的成年患者。从alloSCT到HHV-6激活的中位时间为34天。31例患者的血浆样本中存在HHV-6,9例患者的骨髓(BM)中存在HHV-6,33例患者的支气管肺泡灌洗液、肝脏或肠道活检标本中存在HHV-6,7例患者的脑脊液中存在HHV-6。29例患者发生了急性移植物抗宿主病(GVHD),主要为III-IV级,15例患者同时发生了巨细胞病毒激活。绝对CD3淋巴细胞计数的中位数为207个细胞/µL。我们报告了以下临床表现:43例患者发热,22例患者出现皮疹,19例患者出现肝炎,24例患者出现腹泻,10例患者出现脑炎,18例患者出现BM抑制,11例患者出现植入延迟。37例患者接受了抗病毒药物治疗;尽管如此,该人群的死亡率相对较高(1年总生存率[OS]为38%±7%)。HHV-6激活时CD3细胞计数≥200/µL与更好的OS显著相关(P = 0.0002)。OS也受到无III-IV级急性GVHD(P = 0.03)和完全疾病缓解(P = 0.03)的积极影响,但不受类固醇给药、alloSCT后的时间、抗病毒预防类型、血浆病毒载量或器官受累情况的显著影响。尽管HHV-6检测通常在alloSCT后早期出现,但更好的T细胞免疫重建似乎有可能改善临床结局。我们的研究结果为HHV-6与移植免疫系统之间的相互作用提供了新的见解。

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