de Pagter P J Anne, Schuurman Rob, Visscher Henk, de Vos Machiel, Bierings Marc, van Loon Anton M, Uiterwaal Cuno S P M, van Baarle Debbie, Sanders Elisabeth A M, Boelens JaapJan
Department of Immunology/Haematology and BMT, University Medical Center Utrecht, Utrecht, The Netherlands.
Biol Blood Marrow Transplant. 2008 Jul;14(7):831-9. doi: 10.1016/j.bbmt.2008.04.016.
Human herpes virus 6 (HHV6) is known to reactivate after hematopoietic stem cell transplantation (HSCT), and has been suggested to be associated with severe clinical manifestations in adults. The clinical significance in children remains unclear. We investigated the incidence of HHV6 reactivation in relation to HSCT-associated morbidity and mortality in children. Between January 2004 and May 2006, 58 pediatric patients, median age 7.6 years (range: 0.1-18.1 years), received their first allogeneic HSCT. After HSCT, HHV6, Epstein Barr Virus (EBV), cytomegalovirus (CMV), and adenovirus (AdV)-plasma loads were weekly measured by quantitative PCR. Clinical features, engraftment, graft-versus-host disease (GVHD), and HSCT-associated mortality and morbidity were monitored. HHV6 reactivations were classified in group I (no reactivation), group II (loads <1000 cp/mL) and group III (loads >1000 cp/mL). CMV, EBV, Herpes Simpex Virus, Varicella Zoster Virus, and AdV-reactivations were treated according to local guidelines. HHV6 was treated only when there was clinical suspicion of disease. Thirty-six HLA-identical and 22 HLA nonidentical grafts were transplanted of which 43 were bone marrow or peripheral blood stem cells grafts and 15 were cord blood (CB) grafts. Median follow-up of the patients was 15.5 (1-35) months. HHV6 reactivation occurred in 39 of 58 (67%) patients with 31 of 39 (80%) occurring within the first 30 days post-HSCT. In 26 of 58 (45%) patients (group III), HHV 6 reactivation was significantly associated with higher nonrelapse mortality (P = .02), using multivariate Cox proportional hazard models and grade 2-4 acute GVHD (P = .03) and chronic GVHD (P = .05) in a multivariate logistic regression analysis. HHV6 reactivation is very common after HSCT in children and is associated with serious transplantation-related morbidity and mortality. Although the exact role of HHV6 reactivation after HSCT has to be elucidated, early detection and initiation of therapy might be of benefit.
已知人类疱疹病毒6型（HHV6）在造血干细胞移植（HSCT）后会重新激活，并且有人提出它与成人的严重临床表现有关。其在儿童中的临床意义仍不明确。我们调查了HHV6重新激活的发生率与儿童HSCT相关的发病率和死亡率之间的关系。在2004年1月至2006年5月期间，58名儿科患者（中位年龄7.6岁，范围：0.1 - 18.1岁）接受了首次异基因HSCT。HSCT后，通过定量PCR每周测量HHV6、爱泼斯坦 - 巴尔病毒（EBV）、巨细胞病毒（CMV）和腺病毒（AdV）的血浆载量。监测临床特征、植入情况、移植物抗宿主病（GVHD）以及HSCT相关的死亡率和发病率。HHV6重新激活分为I组（无重新激活）、II组（载量<1000 cp/mL）和III组（载量>1000 cp/mL）。CMV、EBV、单纯疱疹病毒、水痘带状疱疹病毒和AdV的重新激活根据当地指南进行治疗。仅在临床怀疑有疾病时才对HHV6进行治疗。共移植了36个HLA相同和22个HLA不同的移植物，其中43个是骨髓或外周血干细胞移植物，15个是脐血（CB）移植物。患者的中位随访时间为15.5（1 - 35）个月。58名患者中有39名（67%）发生了HHV6重新激活，其中39名中的31名（80%）在HSCT后的前30天内发生。在58名患者中的26名（45%）患者（III组）中，使用多变量Cox比例风险模型，HHV6重新激活与较高的非复发死亡率显著相关（P = 0.02），在多变量逻辑回归分析中与2 - 4级急性GVHD（P = 0.03）和慢性GVHD（P = 0.05）相关。HHV6重新激活在儿童HSCT后非常常见，并且与严重的移植相关发病率和死亡率有关。尽管HSCT后HHV6重新激活的确切作用有待阐明，但早期检测和开始治疗可能有益。
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