Key Takeaways & Executive Findings
- •• The incidence of non-primary infiltration-related central nervous system diseases after allogeneic hematopoietic stem cell transplantation was 6.4% (19/298), with a median onset time of 16 days post-transplant. • Key risk factors included delayed granulocyte and platelet engraftment, prior central nervous system leukemia, and grade III-IV graft-versus-host disease. • The cumulative mortality in affected patients was 47%, significantly higher than 28.6% in controls, and overall survival at 1 and 2 years was markedly lower. • Etiologies included calcineurin inhibitor-related encephalopathy, infections, thrombotic microangiopathy, and intracranial hemorrhage, emphasizing the need for early etiological diagnosis and targeted intervention.
Abstract
BACKGROUND: Allogeneic hematopoietic stem cell transplantation may be complicated by central nervous system diseases 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 non-primary infiltration-related central nervous system diseases after allogeneic hematopoietic stem cell transplantation, in order to provide evidence-based basis for early clinical diagnosis, etiological intervention, and prognosis improvement. METHODS: A retrospective analysis was conducted on clinical data, laboratory characteristics, and treatment processes of 298 patients with hematological diseases who developed non-primary infiltration-related central nervous system diseases after allogeneic hematopoietic stem cell transplantation from January 2015 to June 2024. They were divided into a non-primary infiltration-related central nervous system disease group (n=19) and a control group (without such diseases, n=279). Risk factors were analyzed statistically, and clinical symptoms, possible causes, and prognosis were evaluated. RESULTS AND CONCLUSION: (1) Among 298 patients, 19 developed non-primary infiltration-related central nervous system diseases, with an incidence of 6.4%. (2) The median onset time was 16 days (2-45 days) after transplantation. The main initial symptom was convulsions, accompanied by elevated blood pressure, headache, visual decline, consciousness disorders, and psychiatric behavioral abnormalities. (3) Univariate analysis showed significant associations between the occurrence of these diseases and granulocyte engraftment time, platelet engraftment time, history of central nervous system leukemia before transplantation, and grade III-IV graft-versus-host disease. Etiological analysis revealed: calcineurin inhibitor-related encephalopathy (2 cases), central nervous system injury (4 cases), central nervous system infection (4 cases), transplantation-associated thrombotic microangiopathy (4 cases), central nervous system graft-versus-host disease (1 case), intracranial hemorrhage (2 cases), endocrine metabolic encephalopathy (1 case), and unknown cause (1 case). (4) As of the follow-up date, the cumulative mortality in the disease group was 47% (9/19), significantly higher than 28.6% (80/279) in the control group. Further analysis showed that the estimated overall survival rates at 1 and 2 years after transplantation were significantly lower in the disease group than in the control group. In conclusion, non-primary infiltration-related central nervous system diseases after allogeneic hematopoietic stem cell transplantation are caused by multiple transplantation-related factors. Timely identification of pathogenic factors and precise diagnosis and treatment are crucial for improving the prognosis of patients with these complications.
1. Introduction
Allogeneic hematopoietic stem cell transplantation has become an important curative treatment for malignant and non-malignant hematological diseases, such as leukemia and aplastic anemia. With the popularization of haploidentical transplantation technology, the scale of allogeneic hematopoietic stem cell transplantation in China has expanded year by year, and clinical efficacy has significantly improved [1]. However, transplantation-related complications remain a key issue restricting long-term survival. Among them, non-primary infiltration-related central nervous system diseases (NPI-CNS) are complex in etiology, difficult to diagnose, and highly lethal, warranting in-depth investigation.
The pathogenesis of NPI-CNS involves multiple factors, including drug toxicity (e.g., calcineurin inhibitors, chemotherapeutic agents), infections (bacterial/fungal/viral), transplantation-associated thrombotic microangiopathy, and metabolic abnormalities. Studies have shown that approximately 90% of autopsies of patients who died after hematopoietic stem cell transplantation have evidence of central nervous system involvement, and delayed platelet engraftment is an independent risk factor for poor prognosis. However, systematic research on the clinical characteristics, risk factors, and intervention strategies for NPI-CNS remains scarce [2-3]. Therefore, precise identification of pathogenic factors and targeted diagnostic and therapeutic measures are of great significance for improving the prognosis of patients with transplantation-related NPI-CNS complications.
This study retrospectively analyzed clinical data from 298 patients who underwent allogeneic hematopoietic stem cell transplantation, systematically reporting the incidence (6.4%), median onset time (16 days post-transplant), and high mortality (47%) of NPI-CNS, and identifying key risk factors such as delayed granulocyte/platelet engraftment and prior central nervous system leukemia. The aim is to provide evidence-based evidence for early clinical identification, precise intervention, and prognosis improvement.
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Chen Shiyu, Zhang Xiaohan, Li Xiaoqing, Du Xin (2026). Retrospective analysis of central nervous system diseases related to non-primary infiltration after allogeneic hematopoietic stem cell transplantation. Chinese Journal of Tissue Engineering Research. https://doi.org/10.12307/2026.21340
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Frequently Asked Questions
What is the incidence of non-primary infiltration-related central nervous system diseases after allogeneic hematopoietic stem cell transplantation?
In this retrospective study of 298 patients, 19 developed non-primary infiltration-related central nervous system diseases, yielding an incidence of 6.4%.
What are the common symptoms of these central nervous system complications?
The most common initial symptom is convulsions, often accompanied by elevated blood pressure, headache, visual decline, consciousness disorders, and psychiatric behavioral abnormalities.
What are the main risk factors for developing these complications?
Key risk factors include delayed granulocyte engraftment (>4 weeks), delayed platelet engraftment (>12 weeks), a history of central nervous system leukemia before transplantation, and grade III-IV graft-versus-host disease.
What is the prognosis for patients who develop these complications?
The cumulative mortality in affected patients was 47% (9/19), significantly higher than 28.6% (80/279) in controls. Overall survival at 1 and 2 years post-transplant was significantly lower in the affected group.
What are the possible etiologies of these central nervous system diseases?
Etiologies include calcineurin inhibitor-related encephalopathy, central nervous system infections, transplantation-associated thrombotic microangiopathy, intracranial hemorrhage, central nervous system graft-versus-host disease, and endocrine metabolic encephalopathy, among others.
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