Published in Blood Science in 2025, the study led by Zichang Shen examines the impact of central nervous system leukemia (CNSL) on outcomes after umbilical cord blood transplantation (UCBT). CNSL remains a difficult manifestation of acute leukemia because leukemic cells within the CNS can evade systemic chemotherapy and drive relapse. Although allogeneic transplantation is the most effective curative approach for high-risk disease, the influence of prior CNS involvement on post-transplant outcomes has remained uncertain. Shen and colleagues therefore evaluated how a history of CNSL affects long-term prognosis following UCBT. Background and Objective
Prior CNS involvement may compromise post-transplant disease control because CNS-resident leukemic cells may persist despite conditioning and escape graft-versus-leukemia effects. Evidence regarding the impact of CNSL on UCBT outcomes remains limited. This study aimed to determine whether a history of CNS involvement independently affects relapse, CNS recurrence, engraftment, and survival in acute leukemia patients undergoing UCBT. The analysis compared 62 CNSL-positive patients with 124 matched CNSL-negative controls.
Methods
Patients undergoing UCBT between 2015 and 2022 were retrospectively analyzed. Matching was based on age, sex, and leukemia subtype. CNSL was confirmed by cerebrospinal fluid cytology or CNS imaging. Conditioning regimens included busulfan- or irradiation-based approaches with fludarabine and cyclophosphamide. Cyclosporine and mycophenolate mofetil were used for graft-versus-host prophylaxis. Outcomes were evaluated using competing-risk models and Kaplan–Meier estimates.
Engraftment and Early Outcomes
Hematopoietic recovery did not differ meaningfully between groups. Neutrophil engraftment by day 42 was high in both cohorts, occurring in 97.5% of CNSL-negative patients and 91.9% of CNSL-positive individuals, with nearly identical median engraftment times. Platelet recovery followed a similar pattern: by day 60, platelet engraftment reached 71.8% in the CNSL-negative group and 59.7% in the CNSL-positive group. These differences were not statistically significant. Early complications showed no major discrepancies. Rates of acute graft-versus-host disease and chronic graft-versus-host disease were comparable, indicating that prior CNS involvement does not impair the immediate post-transplant course.
（Blood Science. 7(3):e00237, September 2025.）
Results
Despite similar early outcomes, long-term disease control differed sharply. The 4-year cumulative relapse rate was 28.8% in CNSL-positive patients, significantly higher than the 16.8% seen in CNSL-negative patients. This suggests that leukemic persistence within the CNS may contribute to systemic recurrence after UCBT.
（Blood Science. 7(3):e00237, September 2025.）
CNS-specific recurrence showed even greater disparity. The 4-year cumulative incidence of CNS relapse was 14.7% in patients with a history of CNS involvement compared with only 3.7% in controls, representing nearly a fourfold increase. These findings confirm that CNSL is a major driver of post-transplant CNS recurrence.
Multivariate analysis identified three independent predictors of CNS relapse:
• Diagnosis of acute lymphoblastic leukemia (hazard ratio 14.77, p = 0.007)
• Partial or no remission at transplantation (hazard ratio 2.72, p = 0.024)
• History of CNS involvement (hazard ratio 5.71, p = 0.004)
Survival outcomes mirrored these differences. Leukemia-free survival at four years was 42.0% in the CNSL-positive group versus 66.2% in the CNSL-negative group. GVHD-free relapse-free survival was 23.1% compared with 52.0%. Overall survival was also significantly lower at 49.6% versus 69.9%, respectively. Importantly, transplant-related mortality did not differ significantly (24.2% vs 14.5%, p = 0.105), indicating that poorer outcomes in CNSL-positive patients stem primarily from relapse rather than toxicity.
Among post-transplant CNS relapse cases, nearly half involved isolated CNS recurrence, while the remainder showed combined CNS and systemic relapse—patterns associated with high mortality.
Conclusion
A history of CNS leukemia is a strong, independent predictor of inferior outcomes after umbilical cord blood transplantation. Although early engraftment and immediate post-transplant recovery are similar, prior CNS involvement significantly increases systemic relapse, elevates CNS recurrence, and reduces long-term survival. These findings highlight the need for improved CNS-directed conditioning strategies, enhanced prophylaxis, and more intensive monitoring in this high-risk group.
Click the link to view the original article：
https://journals.lww.com/bls/fulltext/2025/09000/a_prognostic_analysis_of_patients_with_acute.1.aspx
