Abstract
Aggressive NK-cell leukemia (ANKL) is a rare and highly malignant lymphoproliferative disorder associated with poor prognosis and high mortality rates. The disease is closely linked to Epstein-Barr virus (EBV) and predominantly affects populations in Asia and Latin America. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has emerged as a promising treatment strategy, yet its efficacy and prognosis in ANKL patients remain to be systematically evaluated. We conducted a systematic review and meta-analysis by searching PubMed, Embase, Web of Science, and the Cochrane Library for studies published up to April 2025. The objective was to evaluate the outcomes of allo-HSCT in patients with ANKL. Six studies met the inclusion criteria. The primary outcomes included overall survival (OS) and progression-free survival (PFS), reported as hazard ratios (HRs), as well as standardized mean differences (SMDs) and median follow-up times for survivors (reported in months with ranges). Depending on the degree of heterogeneity-assessed using the I(2) statistic-random-effects or fixed-effects models were applied. Sensitivity analyses were conducted by sequentially excluding individual studies, and publication bias was assessed using funnel plots. Based on the analysis, a total of six studies comprising 295 ANKL patients who underwent allo-HSCT were included. The SMD for the median follow-up duration among survivors was 1.21 (95% CI: 0.39-2.02), indicating notable variation in follow-up times across studies. Heterogeneity for this outcome was minimal, with an I(2) of 0% and a p-value of 0.6621. Regarding the effect of allo-HSCT on overall survival, the pooled HR was 0.47 (95% CI: 0.32-0.68), demonstrating a statistically significant survival benefit associated with the procedure. Heterogeneity in this analysis was also low (I(2) = 0.0%, p = 0.684), reflecting strong consistency across the included studies. For PFS, the pooled HR was 0.22 (95% CI: 0.12-0.40), again indicating a significant improvement in outcomes. However, moderate heterogeneity was observed in this analysis (I(2) = 68.4%, p = 0.032). Funnel plot analysis revealed no significant evidence of publication bias, suggesting that the included data were robust and not substantially affected by selective reporting. This meta-analysis demonstrates that allo-HSCT significantly improves survival outcomes in patients with ANKL. The pooled hazard ratio of 0.47 indicates a favorable impact on overall survival. Additionally, the median survival time among survivors is notably longer, further supporting the efficacy of allo-HSCT. These results highlight the potential of allo-HSCT as a promising therapeutic strategy for ANKL, emphasizing the need for continued research to refine treatment protocols and enhance patient outcomes.