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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Citation Impact
MSK Authors
  1. Nancy Kernan
    496 Kernan
  2. Farid Boulad
    319 Boulad
  3. Susan E Prockop
    254 Prockop
  4. Kevin Joseph Curran
    105 Curran
  5. Richard O'Reilly
    710 O'Reilly
  6. Barbara Spitzer
    57 Spitzer
  7. Elizabeth Klein
    31 Klein
  8. Maria   Cancio
    33 Cancio
  9. Jaap Jan Boelens
    134 Boelens