LAUSR

Graft-versus-host disease (GVHD) is a well-known complication of hematopoietic cell transplantation (HCT) [1, 2]. GVHD can be classified into acute GVHD (aGVHD) and chronic GVHD (cGVHD), initially based at the day +100 mark, but corroborated more recently based on clinical features [1, 3], with varying incidences and disease patterns. Additionally, HCT also increases the risk of developing certain neurological complications (NCs). Each NC possesses unique risk factors which can indicate a higher likelihood that such will develop. However, while both GVHD and NCs are common complications of HCT and have been well studied, the association of GVHD with postHCT NCs remains to be elucidated. Herein, we conducted a systematic electronic search regarding the occurrence of noninfectious NCs and GVHD in HCT recipients, gauging the concurrence of GVHD with each complication to establish a possible association. The study was conducted as per the PICO criteria [4]. Studies meeting the inclusion criteria consisted of case reports, case series, clinical trials, and retrospective studies; those excluded were systematic reviews, meta-analyses, review articles, and preclinical studies. The NCs that were included in the systematic review were comprised of the following: (a) Seizures, (b) Posterior Reversible Encephalopathy Syndrome (PRES), (c) Myasthenia Gravis (MG), (d) Stroke, and (e) Peripheral Neuropathy (PN). Medline and other databases were searched as per standard protocol, with the retrieval of articles from 1983 to 2017. As per a preliminary ruleset, wherein any eligible study reporting the frequency of GVHD in the patients affected by the NC under consideration were considered, data from 84 articles were extracted. Then, where available, data on the concurrent reporting of GVHD occurrence in patients both with and without the complication of interest were retrieved, to analyze a post-HCT GVHD occurrence more viable for measures of statistical association, as shown in Table 1. From our preliminary analysis, aGVHD frequency per complication were found to be as follows: Seizures (173/ 267; 64.79%); PRES (65/116; 56.03%); MG (8/10; 80%); Stroke (26/59; 44.06%); PN (60/123; 48.78%). The cGVHD frequencies were found to be as follows: Seizures: 21/29 (72.41%); PRES: 15/69 (21.74%); MG: 15/ 17 (88.24%); Stroke: 21/59 (35.59%); and PN: 74/103 (71.84%). Secondary analysis then of the subset of articles wherein there was concurrent reporting of GVHD in both NCpositive and NC-negative patients revealed a statistically significant association between the following: concurrence of aGVHD and seizures (P < 0.00001); cGVHD and seizures (P= 0.00024); aGVHD and PRES (P= 0.0002); and cGVHD and stroke (P < 0.00001). A lack of adequate data precluded analysis of the concurrence of GVHD with PN and of aGVHD with MG. aGVHD and cGVHD is prevalent amongst HCT recipients, with notable differences in frequencies amongst patients experiencing each NC studied [5]. The complex association of GVHD within the pathophysiologic framework of the NCs listed above has been described in the literature. For example, the development of hemorrhagic stroke, which is far more common in patients with GVHD, can occur due to cerebral microvascular injury leading to a * Shahrukh K. Hashmi [email protected]