Program DHC-Virtual
20 - 21 January 2021
Abstracts Immunology session 2
Abstract
CD4 T cell immune reconstitution predicts survival after aGvHD
20 January
11:54 12:06
C. de Koning
Paper


CD4+ T-cell reconstitution predicts Survival Outcomes after acute Graft-versus-Host-Disease; a dual center validation


Coco de Koning (1), Susan Prockop (2), Ichelle van Roessel (2), Nancy Kernan (2), Elizabeth Klein (2), Jurgen Langenhorst (1), Celina Szanto (1,3), Mirjam Belderbos (3), Marc Bierings (3), Farid Boulad (2), Dorine Bresters (3), Maria Cancio (2), Kevin Curran (2), Wouter Kollen (3), Richard O'Reilly (2), Andromachi Scaravadou (2), Barbara Spitzer (2), Birgitta Versluijs (3), Alwin Huitema (4,5), Caroline Lindemans (3), Stefan Nierkens (1,3), Jaap Jan Boelens (2,3)
(1) UMC Utrecht, Center for Translational Immunology, Utrecht, (2) MSKCC, Pediatric Stem Cell Transplant and Cellular Therapies, New York, (3) Princess Maxima Center for Pediatric Oncology, Pediatric Stem Cell Transplant, Utrecht, (4) UMC Utrecht, Department of Clinical Pharmacy, Utrecht, (5) Netherlands Cancer Institute, Department of Pharmacy & Pharmacology, Amsterdam
No potential conflicts of interest
Introduction

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.

Methods

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.

Results

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).

Conclusion

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.

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