The Related Factors and the Prognosis of Nervous System Complications on the Pediatric Patients with Hematopoietic Stem Cell Transplantation

Objective: To investigate the incidence, clinical characteristics and prognosis of nervous system (NS) complications after hematopoietic stem cell transplantation (HSCT) in children.

Methods: Three hundred children who received HSCT from October 2010 to June 2018 were retrospectively analyzed to identify NS complications in our center. Factors which may be related to NS complications were figured out. Median follow-up time is 3.9 years (range, 0.2- 7.7 years).

Results: Among 300 cases with transplantation, 290 cases were allogeneic transplantation, 9 Autologous transplantation and one case with Isogenic transplantation. The median age was 8 years old (0.7-16 years old), and median weight was 25kg (7-88kg).47.33% of them were male(142/300). Of 290 allogeneic transplantation, 79 cases received sibling matched transplantation, 90 cases received non-relative cord blood transplantation, and 121 cases were haploididentical transplantation. Diseases distribution was as following: 48 cases with aplastic anemia (AA), 174 cases with acute leukemia(AL), 4 cases with chronic myelocytic leukemia (CML), 1 case with juvenile Myelomonocytic Leukemia (JMML),12 cases with myelodysplastic/myeloproliferative neoplasm(MDS/MPN), 28 cases with Wiskott-Aldrich syndrome(WAS), 5 cases with Fanconi anemia (FA), 6 cases with thalassemia, 5 cases with neuroblastoma, one case with neuroblastoma and acute myeloid leukemia, 16 cases with other congenital disorders. Twenty six children developed NS complications after HSCT which accounted for 8.67% (26/300). The diseases which developed NS complications from high to low were as following: FA (33.3%), MDS/MPN (19.2%), AL (7.3%), AA (7.0%), 3.1% in genetic immunodeficiency disease. The average age of children who developed NS complications was 8.3±3.8years old which was older than non- NS complications (6.5±4.0 years old) (p=0.02). Different types of NS complications included 23.1% of demyelinating encephalopathia, 30.8% of cerebral acute graft versus host disease(GVHD), 15.4% of hypertension encephalopathia,11.5% of cerebrovascular lesion, one case of transplantation associated thrombotic microangiopathy (TA-TMA),7.7% of drug therapy-related toxic encephacopathy,3.8% of metabolic encephalopathy,7.7% of peripheral neuropathy. The mortality of NS complications was 34.6%. Of 8 cases with cerebral GVHD, 5 cases died which had the highest mortality (62.5%). No patients with drug therapy-related toxic encephacopathy, metabolic encephalopathy, and peripheral neuropathy died. The overall survival in children with NS complications is lower than the children without NS complications after HSCT (65.4% vs 84.2%, p=0.015).

Conclusions: The incidence of NS complications after HSCT was correlated with primary diseases and children's age. Patients with drug therapy-related toxic encephacopathy, metabolic encephalopathy and peripheral neuropathy had better prognosis than cerebral GVHD and TA-TMA patients. Reduction of NS complications may improve long term survival of children after HSCT.