CD4(+) T-cell reconstitution predicts survival outcomes after acute graft-versus-host-disease: A dual-center validation Journal Article
| Authors: | de Koning, C.; Prockop, S.; van Roessel, I.; Kernan, N.; Klein, E.; Langenhorst, J.; Szanto, C.; Belderbos, M.; Bierings, M.; Boulad, F.; Bresters, D.; Cancio, M.; Curran, K.; Kollen, W.; O'Reilly, R.; Scaradavou, A.; Spitzer, B.; Versluijs, B.; Huitema, A.; Lindemans, C.; Nierkens, S.; Boelens, J. J. |
| Article Title: | CD4(+) T-cell reconstitution predicts survival outcomes after acute graft-versus-host-disease: A dual-center validation |
| Abstract: | 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 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. Key Points: • Early CD4+ IR predicts OS and NRM after moderate to severe aGVHD. • Approaches to augment early and predictable CD4+ IR could improve survival in patients developing aGVHD. © 2021 American Society of Hematology |
| Journal Title: | Blood |
| Volume: | 137 |
| Issue: | 6 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2021-02-11 |
| Start Page: | 848 |
| End Page: | 855 |
| Language: | English |
| DOI: | 10.1182/blood.2020007905 |
| PUBMED: | 33150379 |
| PROVIDER: | scopus |
| PMCID: | PMC7986048 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 March 2021 -- Source: Scopus |
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