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 in patients who developed aGvHD. Pediatric patients receiving their first allogeneic HCT at the UMC Utrecht / Princess Máxima Center (UMC/PMC) or Memorial Sloan Kettering Cancer Center (MSK), were included. 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 with or 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 associates with significantly higher NRM; 74% vs 12% (p<0.001), and inferior OS; 24% vs 78% (p<0.001). In this retrospective analysis we demonstratethat early CD4+ IR, a simple and robust markerpredictive of outcomes after HCT,associates with survival after moderate to severe aGvHD.These associations need to be confirmed in a prospective manner but suggest that strategies to improve T-cell recovery after HCT may influence survival in patients developing aGvHD.