Abstract: BACKGROUND: Allogeneic hematopoietic stem cells may be transplanted with complications of the central nervous system that are not related to primary disease infiltration. There is no clear conclusion on the clinical symptoms, possible causes, and prognosis.
OBJECTIVE: To explore the clinical characteristics, risk factors, and prognosis of complications related to non-primary infiltration of central nervous system after allogeneic hematopoietic stem cell transplantation, in order to provide evidence-based basis for early clinical diagnosis, etiological intervention, and prognosis improvement.
METHODS: The clinical data, laboratory characteristics, and treatment process of 298 hematopathy patients with non-primary infiltration-related central nervous system complications after allogeneic hematopoietic stem cell transplantation from January 2015 to June 2024 were retrospectively analyzed. They were divided into the non-primary infiltration-related central nervous system complication group (n=19) and the control group (no non-primary infiltration-related central nervous system complications, n=279). The risk factor analysis was carried out through statistical methods. The clinical symptoms, possible causes of the disease, and prognosis of the patients were evaluated. 
RESULTS AND CONCLUSION: (1) Among the 298 patients undergoing allogeneic hematopoietic stem cell transplantation, 19 cases experienced central nervous system complications related to non-primary infiltration, with an incidence rate of 6.4%. (2) The median time of onset was 16 days after transplantation (2-45 days). Patients mainly use convulsions as the first symptom, accompanied by increased blood pressure, headache, vision loss, consciousness disorders, and mental behavior abnormalities. (3) Univariate analysis showed that the time of granule implantation, platelet implantation time, history of central nervous system leukemia before transplantation, and the occurrence of graft-versus-host disease in degree III-IV were significantly associated with the incidence of central nervous system complications related to non-primary infiltration. The results of specific etiology analysis show that 2 cases of calcitric acid inhibitor-related encephalopathy, 4 cases of central nervous system damage, 4 cases of central nervous system infection, 4 cases of transplant-related thrombotic microvascular disease, 1 case of graft-versus-host disease in the central nervous system, 2 cases of intracranial hemorrhage, 1 case of endocrine and metabolism-related encephalopathy, and 1 case of unknown cause. (4) As of the follow-up date, the cumulative mortality rate of 19 patients with non-primary infiltration-related central nervous system complications after allogeneic hematopoietic stem cell transplant was 47% (9/19), which was significantly higher than the cumulative mortality rate of 28.6% (80/279) in the control group. Further analysis showed that the expected overall survival rates of patients with the non-primary infiltration-related central nervous system complication group were significantly lower than those of the control group. In short, the central nervous system complications related to non-primary infiltration after allogeneic hematopoietic stem cell transplantation are a rare, difficult to diagnose and highly lethal acute central nervous system disease, which is caused by a variety of transplant-related factors. Timely identification of pathogenic factors and accurate diagnosis and treatment is crucial to improve the prognosis of patients with transplant-related non-primary infiltration of central nervous system complications.

Key words: allogeneic hematopoietic stem cell transplantation (Allo-HSCT), non-primary infiltrating central nervous system disease (NPI-CNS), graft-versus-host disease (GVHD), thrombotic microangiopathy (TMA), calcineurin inhibitor-associated encephalopathy, central nervous system infection, posterior reversible encephalopathy syndrome (PRES), central nervous system leukemia (CNSL)