Clinical characteristics and outcomes of cerebral venous sinus thrombosis in hematologic malignancy patients pre- and post-hematopoietic stem cell transplantation: A single-center retrospective study in China Free

Introduction:

Cerebral venous sinus thrombosis (CVST) is a rare but life-threatening complication in patients with hematologic malignancies, particularly following hematopoietic stem cell transplantation (HSCT). While HSCT offers curative potential for hematologic diseases, its associated prothrombotic risks—including conditioning regimens, immunosuppressive therapy (e.g., cyclosporine), and graft-versus-host disease (GVHD)—may exacerbate CVST susceptibility. This study aimed to evaluate risk factors, clinical features, potential sequelae, duration of anticoagulation, optimal timing for HSCT, transplantation strategies, and recurrence risks during and after transplantation, as well as their impact on posttransplantation survival in patients who developed CVST before or after HSCT.

Methods:

From 2013 to 2023, a total of 29 patients with hematologic malignancies who developed CVST during the course of their treatment were included in the study. The diagnoses comprised acute lymphoblastic leukemia (ALL, n=15; 51.72%; allo-HSCT=8), myelodysplastic syndrome (MDS, n=4; 13.79%; allo-HSCT=4), acute myeloid leukemia (AML, n=3; 10.34%; including APL=2, AML-MR=1, allo-HSCT=1), and other conditions. Subgroup analysis was conducted on six cases of pre-HSCT CVST (ALL, n=6) and three cases of post-HSCT CVST (MDS, n=2; AML-MR, n=1).

Results:

Six pre-HSCT CVST patients diagnosed with ALL (male: n=4; female: n=2) demonstrated a median age of 15 years (range: 7-31 years). Four cases (67%) occurred during the induction phase of leukemia treatment, and 2 cases (33%) occurred during the consolidation phase. All patients were receiving chemotherapy regimens containing pegaspargase at the time of CVST onset. Predominant clinical manifestations comprised headache (n=5), altered consciousness (n=3), and seizures (n=3) as neurologic presentations, accompanied by sensorimotor deficits (limb numbness/weakness, n=2), dysarthria (n=2), and gastrointestinal symptoms (vomiting, n=2). MRV findings demonstrated multiple sinus involvement in 4 patients (superior sagittal sinus=4, transverse=3, sigmoid=3), isolated superior sagittal sinus thrombosis in 1, with imaging unavailable for 1 patient. Intracranial hemorrhage was present in 4 cases (data missing in 1). The pre-HSCT CVST cohort (n=6) demonstrated heterogenous management: 1 spontaneous resolution without therapy (2-day symptom remission), 5 anticoagulation cases (>3 months duration) including 1 endovascular intervention. Thrombus resolution was radiologically confirmed pre-HSCT (median CVST-to-transplant interval:6.9 months). Longitudinal follow-up (median 3.88 years) revealed 1 mortality from post-second-HSCT sepsis, with others maintaining CR without thrombotic recurrence. Among the three post-HSCT CVST cases, one MDS patient developed CVST 2.5 months following HSCT, presenting with elevated cyclosporine levels, immune-mediated thrombocytosis, and grade II gastrointestinal aGVHD. The case achieved 3.64 years of thrombosis-free survival following a 12-month course of anticoagulation therapy. A second MDS patient presented with CVST at 14 months post-transplantation, concurrent with lower extremity deep vein thrombosis (DVT), consistent with chronic GVHD (cGVHD)-associated vasculopathy. This case maintained 2.67 years of disease-free survival after anticoagulation. The third patient had a history of MDS that transformed into AML-MR. Thirteen years after the initial HSCT, the patient exhibited clinical features of CVST. Radiological and clinical evaluations confirmed disease recurrence, and a salvage second HSCT was performed 3.6 months after diagnosis. No CVST recurrence was observed during the subsequent 0.67-year follow-up. All patients received guideline-concordant anticoagulation therapy and remained alive at the end of the follow-up period.

Conclusions:

Pegaspargase-based regimens significantly elevate CVST risk in ALL management. The post-HSCT CVST may be associated with calcineurin inhibitor toxicity (early phase), cGVHD pathophysiology (chronic phase), and disease relapse. Most patients demonstrate favorable outcomes with appropriate anticoagulation therapy. The administration of conventional HSCT conditioning regimens with standard GVHD prophylaxis enables the safe implementation of allogeneic transplantation at a median interval of 6.9 months post-CVST treatment, demonstrating neither thrombotic recurrence nor procedure-related mortality in our cohort.