• Coco de Koning, Susan Prockop, Ichelle van Roessel, Nancy Kernan, Elizabeth Klein, Jurgen Langenhorst, Celina Szanto, Mirjam Belderbos, Marc Bierings, Farid Boulad, Dorine Bresters, Maria Cancio, Kevin Curran, Wouter Kollen, Richard O'Reilly, Andromachi Scaradavou, Barbara Spitzer, Birgitta Versluijs, Alwin Huitema, Caroline Lindemans, Stefan Nierkens, and Jaap Jan Boelens.
• Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
• Blood. 2021 Feb 11; 137 (6): 848-855.

AbstractAcute 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 immune reconstitution (IR; CD4+ IR) predicts survival after HCT. Here, we studied the relation between CD4+ IR and survival in patients developing aGVHD. Pediatric patients undergoing first allogeneic HCT at University Medical Center Utrecht (UMC)/Princess Máxima Center (PMC) or Memorial Sloan Kettering Cancer Center (MSK) were included. Primary outcomes were nonrelapse mortality (NRM) and overall survival (OS), stratified for aGVHD and CD4+ IR, defined as ≥50 CD4+ T cells per μL within 100 days after HCT or before aGVHD onset. Multivariate and time-to-event Cox proportional hazards models were applied, and 591 patients (UMC/PMC, n = 276; MSK, n = 315) were included. NRM in patients with grade 3 to 4 aGVHD with or without CD4+ IR within 100 days after HCT was 30% vs 80% (P = .02) at UMC/PMC and 5% vs 67% (P = .02) at MSK. This was associated with lower OS without CD4+ IR (UMC/PMC, 61% vs 20%; P = .04; MSK, 75% vs 33%; P = .12). Inadequate CD4+ IR before aGVHD onset was associated with significantly higher NRM (74% vs 12%; P < .001) and inferior OS (24% vs 78%; P < .001). In this retrospective analysis, we demonstrate that early CD4+ IR, a simple and robust marker predictive of outcomes after HCT, is associated with survival after moderate to severe aGVHD. This association must be confirmed prospectively but suggests strategies to improve T-cell recovery after HCT may influence survival in patients developing aGVHD.© 2021 by The American Society of Hematology.

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