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

Abstract

Neurologic complications (NCs) may be a significant source of morbidity and mortality after hematopoietic cell transplantation (HCT). We performed a retrospective study of 263 consecutive patients undergoing allogeneic HCT for hematological malignancies to determine the incidence, risk factors and clinical impact of NCs in the first 5 years after HCT. We determined the incidence of central nervous system (CNS) infection, intracranial hemorrhage, ischemic stroke, metabolic encephalopathy, posterior reversal encephalopathy syndrome, seizure and peripheral neuropathy. In all, 50 patients experienced 63 NCs-37 early (⩽day +100), 21 late (day +101 to 2 years) and 5 very late (2 to 5 years). The 1- and 5-year cumulative incidences of all NCs were 15.6% and 19.2%, respectively, and of CNS complication (CNSC; all of the above complications except peripheral neuropathy) were 12.2 and 14.5%. Risk factors for CNSC were age (hazard ratio (HR)=1.06 per year, P=0.0034), development of acute GvHD grade III-IV (HR=2.78, P=0.041), transfusion-dependent thrombocytopenia (HR=3.07, P=0.025) and delayed platelet engraftment (>90th centile; HR=2.77, P=0.043). CNSCs negatively impacted progression-free survival (HR=2.29, P=0.0001), overall survival (HR=2.63, P<0.0001) and non-relapse mortality (HR=8.51, P<0.0001). NCs after HCT are associated with poor outcomes, and usually occur early after HCT.

Noninfectious Neurologic Complications after Allogeneic Hematopoietic Stem Cell Transplantation

“…The rate of NCs in our study (7.5% at 3 months and 13% at 5 years after allo-HSCT) is within the wide range reported previously [4,7,8,23,24]; however, comparisons across studies are difficult owing to the heterogeneity of patient and transplantation characteristics, definitions of neurologic events, and duration of follow-up. In this study, we only considered primary NCs occurring after allo-HSCT, excluding NCs due to CNS infection, as reported previously [6], and NCs due to relapse of the baseline disease.…”

“…Regarding the frequency of the different complications, we detected a higher incidence of PNS NCs (32% of all NCs) than in other studies [7,8], likely due to the delayed onset of PNS events and the longer duration of follow-up in our study.…”

“…We previously reported the incidence of (4.9% at 5 years) and risk factors for infectious central nervous system (CNS) NCs in the allo-HSCT setting, which include receiving an umbilical cord blood (UCB) transplantation and disease stage beyond first complete remission [6]. Although some studies have reported the incidence of and risk factors for noninfectious NCs [1,[7][8][9], data derived from the analysis of larger cohorts are missing.…”

Radiation causes tissue damage by dysregulating inflammasome–gasdermin D signaling in both host and transplanted cells

“…TBI followed by HSC transplantation is also recommended for the treatment of nonmalignant blood disorders, including hemoglobinopathies, aplastic anemia, and immune deficiencies [3,4]. Thus, TBI-containing conditioning regimens are widely used in the clinic, yet they cause life-threatening injuries and side effects in multiple organs, including the intestine, lungs, kidney, brain, and spleen [2,[4][5][6][7].…”

Recent Topics on The Mechanisms of Immunosuppressive Therapy-Related Neurotoxicities

“…Furthermore, the risk of neurological complications was shown to be 81% in patients during 18 years of follow-up. Common complications seen with all types of transplantation include alterations of consciousness, seizures, encephalopathy, and cerebrovascular events [9,10,11,12]. The etiologies of neurological complications are diverse, including immunosuppressant-related neurotoxicity [13,14], infections [15], metabolic disorders, hemorrhages [9], and primitive diseases prior to the transplant.…”