CD4+ T-cell reconstitution predicts Survival Outcomes after acute Graft-versus-Host-Disease; a dual center validation
Acute Graft-versus-Host-Disease (aGvHD) is a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). We previously showed that early CD4+ T-cell reconstitution (CD4+ IR) predicts survival after HCT. Here, we studied the relation between CD4+ IR and survival outcomes in patients who developed aGvHD.
Pediatric patients receiving their first allogeneic HCT at the UMC Utrecht / Princess Máxima Center (UMC/PMC) and at Memorial Sloan Kettering Cancer Center (MSK), New York were included. The primary outcomes were non-relapse mortality (NRM) and overall survival (OS), stratified for aGvHD and CD4+ IR; defined as ³50 CD4+ T-cells/uL within 100 days after HCT, or prior to aGvHD onset. Multivariate and time-to-event Cox Proportional Hazard models were applied.
591 Patients (N= 276 UMC/PMC; N= 315 MSK) were included. NRM in patients with aGvHD grade III-IV in patients with and without CD4+ IR within 100 days after HCT was 30% vs 80% (p=0.02) at UMC/PMC and 5% vs 67% (p=0.02) at MSK. This associated with lower OS without CD4+ IR; 61% vs. 20% (p=0.04) at UMC/PMC, and 75% vs. 33% (p=0.12) at MSK. Inadequate CD4+ IR prior to aGvHD onset associated with a significantly increased risk of NRM; 74% vs 12% (p<0.001), and inferior OS; 24% vs 78% (p<0.001).
In conclusion, we have now demonstrated in a retrospective analysis of two independent cohorts, that early CD4+ IR, a simple and robust biomarker predictive of outcomes after HCT, is also associated with survival after moderate to severe aGvHD. While these findings need to be confirmed in a prospective manner, they suggest that strategies to improve T-cell recovery after HCT may influence survival chances in patients suffering from aGvHD.