Long‐term brain status and cognitive impairment in children treated for high‐risk acute lymphoblastic leukemia with and without allogeneic hematopoietic stem cell transplantation: A single‐center study

Abstract

Aim The aim of the study was to assess long-term consequences of central nervous system (CNS) prophylaxis in patients with high-risk ALL (HR-ALL) treated according to ALL IC-BFM 2002 and to compare observed abnormalities in patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) with those who received only prophylactic CNS irradiation (12 Gy) and with control group. Patients and methods We studied 29 patients with HR-ALL in CR1 after treatment according to protocol ALL IC-BFM 2002 (14 with allo-HSCT conditioned with fractionated total body irradiation [FTBI] and 15 without HSCT) and 16 children with newly diagnosed ALL (control group). The median time from therapy completion to evaluation was 5 years. To assess brain status, volumetric T1-weighted sequences of magnetic resonance imaging were used. Neuropsychological assessment based on battery neuropsychological tests. Results Transplanted patients had significantly lower volumes of white and gray matter (P = .048 and P < .001) and also of subcortical structures, including the thalamus (P < .001), the hippocampus (P = .007), the putamen (P = .011), the globus pallidus (P = .001), and the accumbens (P < .001). In addition, these patients had generally lower cognitive performance, especially in vocabulary (P = .011), visuospatial ability (P = .047), executive functions and attention (P = .034; P = .002; P = .048), and processing speed (P = .049 and P = .037). The thalamus volume is correlated with neuropsychological performance in verbal functions (P < .001), executive functions (P < .001 and P = .024), and processing speed (P < .001). Conclusions In pediatric patients treated for ALL, FTBI-based preparative regimen preceding allo-HSCT causes reduction of subcortical structure volumes and decline in cognitive performance. The observed long-term structural and functional CNS sequelae are significantly more pronounced in transplanted HR-ALL patients than in those treated with prophylactic CNS- radiotherapy only.