Neurological complications following pediatric allogeneic hematopoietic stem cell transplantation: Risk factors and outcome

Abstract

BackgroundAllogeneic hematopoietic stem cell transplantation (HSCT) is an efficient treatment for numerous malignant and nonmalignant conditions affecting children. This procedure can result in infectious and noninfectious neurological complications (NCs).ObjectiveThe objective of the study is to examine the incidence, risk factors, and outcomes of NCs in pediatric patients following allogeneic HSCT.MethodsWe performed a retrospective study of 746 children who underwent 943 allogeneic HSCTs in two large pediatric hospitals in Israel from January 2000 to December 2019.ResultsOf the pediatric patients 107 (14.3%) experienced 150 NCs. The median follow-up was 55 months. Noninfectious NCs were more common than infectious NCs (81.3% vs. 18.7%). Factors significantly associated with type of NC (infectious vs. noninfectious) were underlying disease (immunodeficiency vs. malignant and metabolic/hematologic disease) (p-value = 0.000), and use of immunosuppressive agent, either Campath or ATG (p-value = 0.041). Factors with a significant impact on developing neurological sequelae post-NC were number of HSCT >1 (p-value = 0.028), the use of alemtuzumab as an immunosuppressive agent (p-value = 0.003), and infectious type of NC (p-value = 0.046). The overall survival rate of whole NC-cohort was 44%; one-third of all mortality cases were attributed to the NC. The strongest prognostic factors associated with mortality were older age at HSCT (p-value = 0.000), the use of alemtuzumab as an immunosuppressive agent (p-value = 0.004), and the existence of neurological sequelae (p-value = 0.000). Abnormal central nervous system imaging (p-value = 0.013), the use of alemtuzumab as an immunosuppressive agent (p-value = 0.019), and neurological sequelae (p-value = 0.000) had statistically significant effects on neurological cause of death.ConclusionInfectious and noninfectious NCs are a significant cause of morbidity and mortality following allogeneic HSCT in children. Further research is required to better understand the risk factors for different NCs and their outcomes regarding sequelae and survival.

Viral meningoencephalitis in pediatric solid organ or hematopoietic cell transplant recipients: a diagnostic and therapeutic approach

“…Among HCT recipients who experience neurological complications, a lower incidence reported in the first year post-transplant compared to later time points ( 1 – 6 ). In an Israeli study spanning two decades and including more than 700 pediatric HCT recipients, non-infectious complications were found to be more common (81.3%) compared to infectious complications (18.7%) ( 7 ). Factors commonly associated with increased risk of neurological complications included receipt of myeloablative chemotherapy, use of alemtuzumab, delay in platelet engraftment, presence of acute graft-vs.-host disease (aGvHD), and underlying primary disease ( 7 – 9 ).…”

“…In an Israeli study spanning two decades and including more than 700 pediatric HCT recipients, non-infectious complications were found to be more common (81.3%) compared to infectious complications (18.7%) ( 7 ). Factors commonly associated with increased risk of neurological complications included receipt of myeloablative chemotherapy, use of alemtuzumab, delay in platelet engraftment, presence of acute graft-vs.-host disease (aGvHD), and underlying primary disease ( 7 – 9 ). Non-infectious neurologic sequalae were more common in patients with underlying metabolic or hematologic diseases whereas central nervous system (CNS) infections occurred more frequently in patients with an underlying immunodeficiency.…”