Colombo Anna Amelia, Marchioni Enrico, Diamanti Luca, Di Matteo Angela Maria, Baldanti Fausto, Furione Milena, Cazzola Mario, Ferretti Virginia Valeria, Pascutto Cristiana, Alessandrino Emilio Paolo
1 Transplant Bone Marrow Unit, Department of Hematology Oncology Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. 2 Istituto Neurologico Nazionale, IRCCS "C. Mondino", Pavia, Italy. 3 Neuroscience Consortium, University of Pavia, Monza Policlinico and Pavia Mondino, Pavia, Italy; C. Mondino National Neurological Institute, Pavia, Italy. 4 Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. 5 Molecular Virology Unit, Virology and Microbiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. 6 Department of Hematology Oncology Diseases Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Transplantation. 2017 Mar;101(3):616-623. doi: 10.1097/TP.0000000000001257.
Neurological complications (NC) after hematopoietic stem cell transplantation (HSCT) are rare events. The evolution of transplant procedures has resulted in improved survival and has allowed elderly patients or those with comorbidity to receive an HSCT. The risk of NC in these patients has still not been well defined. Therefore, we carried out an observational study to estimate the occurrence and identify the risks associated with NC.
The study cohort included 452 adult-allogeneic HSCT recipients, transplanted from 1997 to 2012. The median follow up was 1.3 year (0-15.7). A myeloablative regimen was used in 307 patients. Two hundred patients were grafted from matched unrelated donor (MUD), of these, 129 (64.5%) received an in vivo T-cell depletion.
Out of 452 patients, 30 (6.6%) developed NC. Infections were the most frequent causes of NC (30%). Overall survival decreased in patients developing NC (P < 0.001). Univariate survival regression on the cumulative incidence of NC identified period of transplant, linear trend between 4-year periods (1997-2012) (P < 0.001), MUD (P < 0.001), and recipient's age (P = 0.034) as significant risk factors. In multivariate analysis, period of transplant (P < 0.001) and MUD (P = 0.004) remained significant independent risk factors. Matched unrelated donor recipients showed a 3.8-fold elevated risk of developing NC.
Analysis highlights a temporal trend of incidence of NC that progressively increased over time and confirms a strong association between donor type and risk of NC. Our observations suggest that, although relatively uncommon, NC after allo-HSCT, may become more frequent due to the improved overall survival in recent years.
造血干细胞移植（HSCT）后发生神经并发症（NC）是罕见事件。移植程序的发展提高了生存率，并使老年患者或合并症患者能够接受HSCT。这些患者发生NC的风险仍未得到明确界定。因此，我们开展了一项观察性研究，以评估NC的发生率并确定与之相关的风险因素。
研究队列包括1997年至2012年期间接受成人异基因HSCT的452例患者。中位随访时间为1.3年（0 - 15.7年）。307例患者采用了清髓性预处理方案。200例患者接受了来自匹配无关供者（MUD）的移植，其中129例（64.5%）接受了体内T细胞清除。
452例患者中，30例（6.6%）发生了NC。感染是NC最常见的原因（30%）。发生NC的患者总体生存率下降（P < 0.001）。对NC累积发生率进行单因素生存回归分析，确定移植时间、4年时间段（1997 - 2012年）之间的线性趋势（P < 0.001）、MUD（P < 0.001）以及受者年龄（P = 0.034）为显著风险因素。多因素分析中，移植时间（P < 0.001）和MUD（P = 0.004）仍然是显著的独立风险因素。匹配无关供者受者发生NC的风险升高了3.8倍。
分析突出了NC发生率随时间逐渐增加的时间趋势，并证实了供者类型与NC风险之间的密切关联。我们的观察结果表明，尽管异基因HSCT后NC相对不常见，但由于近年来总体生存率的提高，其可能会变得更加频繁。
