Neurologic Complications after Allogeneic Hematopoietic Stem Cell Transplantation in Children: Analysis of Prognostic Factors

Abstract

Neurologic complications are serious complications after hematopoietic stem cell transplantation (HSCT) and significantly contribute to morbidity and mortality. The purpose of this study was to investigate the clinical features and prognosis in pediatric patients who had neurologic complications after allogeneic HSCT. We retrospectively reviewed the medical records of children and adolescents (19 years old or younger) who underwent allogeneic HSCT at our institution from 2000 to 2012. A total of 383 patients underwent 430 allogeneic transplantations. Among them, 73 episodes of neurologic complications occurred in 70 patients. The cumulative incidence of neurologic complications at day 400 was 20.0%. Almost two thirds of the episodes (63.0%, 46 of 73) occurred within 100 days after transplantation. Calcineurin inhibitor-related neurotoxicity was observed as the most common cause of neurotoxicity (47.9%, 35 of 73) and was significantly associated with earlier onset neurologic complications, seizure, and tremor. It also showed a significant association with lower probability of headache, abnormality of cranial nerve, and neurologic sequelae. In a multivariate analysis, days to neutrophil engraftment after HSCT, extensive chronic graft-versus-host disease (GVHD) and the existence of neurologic sequelae were identified as risk factors for mortality in patients who had neurologic complications (hazard ratio [HR], 1.08; 95% confidence interval [CI], 1.02 to 1.15; P = .011; HR, 5.98; 95% CI, 1.71 to 20.90; P = .005; and HR, 4.37; 95% CI, 1.12 to 17.05; P = .034, respectively). However, there was no significant difference in the 5-year overall survival between the patients who had neurologic complications without sequelae and the patients who did not have any neurologic complications (57.3% versus 61.8%, P = .906). In conclusion, we found that the major significant risk factors for mortality in pediatric recipients with neurologic complications were the existence of neurologic sequelae and extensive chronic GVHD.

Neurologic complications after allogeneic hematopoietic stem cell transplantation: risk factors and impact

“…Our cumulative incidence of CNSC of 12.2% at 1 year and 14.5% at 5 years is lower than the majority of prior reports. [34][35][36][37][38][39][40][41][42][43][44][45][46][47][48] This finding is consistent with the overall trend of reduced morbidity and mortality associated with HCT over time. 64 Despite a relatively low overall incidence of NCs we still found that development of a CNSC portends a poor prognosis and was associated with decreased PFS and OS, and increased NRM, consistent with previous studies.…”

“…Several studies have sought to define the incidence and characteristics of NCs associated with HCT, with estimates of incidence varying considerably, from~8 to 65% depending on the study design, types of NCs included, patient population and transplantation setting. [34][35][36][37][38][39][40][41][42][43][44][45][46][47][48] Autopsy studies have uncovered neuropathological findings in as high as 90% of patients who have died following HCT. [49][50][51] Many of these studies have found unfavorable survival among patients who develop central nervous system (CNS) complications (CNSCs).…”

A randomized clinical trial of a parent-focused social-cognitive processing intervention for caregivers of children undergoing hematopoetic stem cell transplantation.

“…Short-term medical complications include severe mucositis, hepatic toxicities, septicemia, and acute GvHD, and/or an unsuccessful engraftment (Eduardo et al, 2015; Peters et al, 2015). Long-term medical complications can include infections (Ferry et al, 2007), pulmonary disease (Srinivasan et al, 2014), chronic GvHD (Alousi, Bolaños-Meade, & Lee, 2013), endocrine disease (Ferry et al, 2007), neurological problems (Kang et al, in press), as well as second malignancies and disease recurrence (Arico et al, 2010). Despite improved survival statistics, pediatric HSCT remains a risky procedure.…”

The confused oncologic patient: a rational clinical approach

“…55,56 Most neurologic complications occur within 100 days of transplant and manifest as seizure and encephalopathy. Seizures are most common immediately after the stem cell infusion and may be related to dimethyl sulfoxide used for cryopreservation.…”