Comparison of Fresh Versus Frozen Allogenic Peripheral Blood Stem Cell Grafts in Hematopoietic Stem Cell Transplantation: A Meta-Analysis and Systematic Review

The COVID-19 pandemic led to the widespread adoption of cryopreserved peripheral blood stem cell (PBSC) grafts in allogeneic hematopoietic stem cell transplantation (HSCT), diverging from the traditional preference for fresh grafts. Although cryopreservation ensures graft availability during logistical disruptions, its impact on transplantation outcomes remains uncertain. Existing studies report mixed findings, and no consensus has been established regarding long-term outcomes. In the present study, we compared clinical outcomes of fresh versus cryopreserved allogeneic PBSC grafts in patients undergoing HSCT, with a focus on engraftment and survival outcomes, and evaluated the consistency of reported effects across studies, through a meta-analysis and systematic review of retrospective cohort studies published between 2005 and 2025. PubMed and Embase were searched through May 10, 2025. Primary outcomes included composite, primary, and secondary graft failure; secondary outcomes included engraftment times, overall survival (OS), and relapse-free survival (RFS). Random-effects and fixed-effects models were conducted using R, and Kaplan-Meier curves were digitized when necessary. Thirteen studies were included in the meta-analysis, and 19 studies were included in the systematic review. Fresh grafts were associated with significantly lower odds of composite graft failure (odds ratio [OR], 0.58), primary graft failure (OR, 0.60), and secondary graft failure (OR, 0.46), all with low heterogeneity. Neutrophil and platelet engraftment times were similar, although platelet engraftment showed a nonsignificant trend favoring fresh grafts (-1.34 days; P = .058). One-year and 2-year OS favored fresh grafts in fixed-effects models (OR, 1.15 and 1.16, respectively), but these associations were not significant under random-effects models owing to substantial heterogeneity. One-year RFS also favored fresh grafts in the fixed-effects model (OR, 1.25) but lost significance in the random-effects model. In contrast, 2-year RFS consistently favored fresh grafts across both models (OR, 1.21; 95% CI, 1.08 to 1.35; I² = 0%). Our findings indicate that fresh PBSC grafts are associated with significantly lower rates of graft failure and may confer long-term survival benefits compared to cryopreserved grafts. While survival outcomes varied by statistical model because of heterogeneity, no studies reported superior outcomes with cryopreserved products. These findings support the preferential use of fresh grafts when feasible. Preclinical and clinical studies are needed to further improve the cryopreservation process. Subgroup analyses also may help identify patient populations most likely to benefit from fresh grafts.