Impact of γδ T cells on clinical outcome of hematopoietic stem cell transplantation: systematic review and meta-analysis

Allogeneic hematopoietic stem cell transplantation (HSCT) using alpha beta T-/B-cell-depleted grafts recently emerged as a transplant strategy and highlighted the potential role of gamma delta T cells on HSCT outcomes. Our aim was to scrutinize available evidence of gamma delta T-cell impact on relapse, infections, survival, and acute graft-versus-host disease (aGVHD). We performed a systematic review and meta-analysis of studies assessing gamma delta T cells in HSCT. We searched PubMed, Web of Science, Scopus, and conference abstracts from inception to March 2019 for relevant studies. We included all studies that assessed gamma delta T cells associated with HSCT. Data were extracted independently by 2 investigators based on strict selection criteria. A random-effects model was used to pool outcomes across studies. Primary outcome was disease relapse. We also assessed infections, survival, and aGVHD incidence. The review was registered with PROSPERO (CRD42019133344). Our search returned 2412 studies, of which 11 (919 patients) were eligible for meta-analysis. Median follow-up was 30 months (interquartile range, 22-32). High gamma delta T-cell values after HSCT were associated with less disease relapse (risk ratio [RR], 0.58; 95% confidence interval [95% CI], 0.40-0.84; P = .004; I-2 = 0%), fewer viral infections (RR, 0.59; 95% CI, 0.43-0.82; P < .002; I-2 = 0%) and higher overall (HR, 0.28; 95% CI, 0.18-0.44; P < .00001; I-2 = 0%) and disease-free survivals (HR 0.29; 95% CI, 0.18-0.48; P < .00001; I-2 = 0%). We found no association between high gd T-cell values and aGVHD incidence (RR, 0.72; 95% CI, 0.41-1.27; P = .26; I-2 = 0%). In conclusion, high gd T cells after HSCT is associated with a favorable clinical outcome but not with aGVHD development, suggesting that gd T cells have a significant effect on the success of HSCT. This study was registered with PROSPERO as #CRD42019133344.