Unveiling new horizons in severe aplastic anemia management: a two-decade study on intensive immunosuppressive therapy combined with unrelated cord blood efficacy

揭示重型再生障碍性贫血治疗的新前景:一项历时二十年的研究表明,强化免疫抑制疗法联合非亲缘脐带血疗法具有显著疗效。

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Abstract

BACKGROUND: In the absence of a human leukocyte antigen (HLA)-matched donor, intensive immunosuppressive therapy (IST) combined with unrelated cord blood (IIST-UCB) a salvage treatment option for patients with severe aplastic anemia (SAA) who had failed IST. With advancements in transplantation technology, outcomes of IIST-UCB have improved considerably in recent years. Here, we will focus on the differential effects of IIST-UCB on patient survival and GVHD risk and evaluate its therapeutic efficacy between SAA and VSAA patients. METHODS: Between August 2004 and May 2024, 115 SAA patients were screened at enrollment. The overall survival (OS) rates and failure-free survival (FFS) rates were evaluated and compared using Kaplan-Meier curves and log-rank tests. Cumulative incidences of cytomegalovirus (CMV), hematopoietic recovery, and Epstein-Barr virus (EBV) were estimated using a competing risk regression model. RESULTS: The median age was 16 years (range, 2-74). At 6 months, 27 patients (27%) achieved complete response (CR), and 44 patients (44%) achieved partial response (PR). The median period to neutrophil engraftment was 25 days, and to platelet engraftment was 44 days. The 250-day cumulative incidence of hemoglobin recovery was 87.8% (95% CI, 77.7%-93.6%). The 100-day cumulative incidence of neutrophil engraftment was 88.5% (95%CI, 80.6%-93.3%). The 400-day cumulative incidences of platelet engraftment was 86.7% (95%CI, 77.5%-92.4%). The 5-year overall survival was 86.1% ± 6.66%, and the 5-year failure-free survival was 72% ± 8.62% in the cohort. Transplantation-related mortality was 12.5% (95% CI, 7.2%-19.4%). No acute or chronic graft-versus-host disease (GVHD) was observed during the entire period. The cumulative incidences of CMV and EBV were 7.18% (95% CI, 3.34%-13%) and 16.8 (95% CI, 10.6%-24.3%), respectively. The majority of patients exhibited microchimerism and maintained hematopoiesis over the long term. Patients with SAA who received UCB treatment showed significantly higher hematopoietic reconstitution efficiency (P = 0.004, P = 0.001, P = 0.001) and overall survival compared with the VSAA group (P = 0.028). CONCLUSION: These data support IIST-UCB as an alternative therapeutic approach for patients with SAA.

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