Çocuklarda Allojenik Hematopoetik Kök Hücre Nakli Sonrası Nörolojik Komplikasyonlar ve Risk Faktörleri

Abstract

AKSAK YİĞİT, G., Neurological Complications and Risk Factors After Allogeneic Hematopoietic Stem Cell Transplantation in Children. Hacettepe University Faculty of Medicine, Department of Pediatrics, Thesis in Pediatrics, Ankara 2024. Hematopoietic stem cell transplantation (HSCT) is a curative treatment method used in various diseases such as malignant diseases, hematologic diseases and immunodeficiencies. Although the success rate of HSCT has increased in recent years, it may still cause complications leading to mortality and morbidity. Among these, neurologic complications (NCs), which are known to occur with a frequency of 9.7-24%, account for 10-15% of HSCT-related mortality. In this study, we aimed to determine the incidence, types, outcomes and risk factors of NCs after allogeneic HSCT. For this purpose, the files of pediatric patients (0-18 years of age) who underwent HSCT between January 1, 2011 and June 1, 2021 at the Pediatric Bone Marrow Transplantation Unit, Hacettepe University Faculty of Medicine, were retrospectively reviewed. Patients who underwent more than one allogeneic HSCT during the study period, who underwent HSCT for neurometabolic disease, who had neurological findings or involvement for any reason and who developed peripheral NC after transplantation were not included in the study. One hunderd and fifty patients were included in the study. Patients were grouped according to the status of NC development. Transplant characteristics (gender, age, primary disease, donor characteristics, recipient-donor gender, stem cell source, preparation regimen and graft versus host disease prophylaxis) and transplant outcomes (engraftment, grade 2 and above (grade ≥ 2) and acute graft versus host disease (aGVHD), chronic GVHD, sinusoidal obstruction syndrome, cytomegalovirus (CMV) reactivation/infection, engraftment syndrome, and abnormal CNS imaging) effects on NC were investigated. NC types were divided into two subgroups: infectious and non-infectious. Transplant characteristics and outcomes on NC types were also examined. The incidence of NC in patients undergoing HSCT was 13.3%. Multivariate logistic regression analysis showed that the risk of developing NC increased six-fold in patients with ≥ grade 2 aGVHD and three-fold in patients with CMV reactivation/infection. Although there was no statistically significant difference in terms of whole body irradiation (TVI), the rate of TVI was found to be three times higher in patients who developed NC compared to patients who did not develop NC. No statistically significant relationship was detected between other variables and NC development. When NCs were grouped as infectious and noninfectious, no significant difference was found between transplant characteristics and transplant outcomes and NC type. Posterior reversible encephalopathy syndrome (PRES) was the most common NC. When NCs were examined in two groups as early (<100 days) and late (>100 days) complications according to their development time, no significant difference was found between the NC types. Mortality rates were significantly higher in patients who developed NC than in patients who did not. 3.3% of all transplanted patients died from NC-related causes. There was no death due to PRES. In conclusion, more attention should be paid in terms of aGVHD and CMV infection, which are risk factors for the prevention of NPCs that cause fatal outcomes after HSCT. This single-center study is one of the rare studies in pediatric patients examining NCs after HSCT. More prospective multicenter prospective studies are needed to better understand the risk factors, morbidity and mortality outcomes for different NCs.