High day 28 ST2 levels predict for acute graft-versus-host disease and transplant-related mortality after cord blood transplantation

Doris M. Ponce, Patrick Hilden, Christen Mumaw, Sean M. Devlin, Marissa Lubin, Sergio Giralt, Jenna D. Goldberg, Alan Hanash, Katharine Hsu, Robert Jenq, Miguel Angel Perales, Craig Sauter, Marcel R M Van Den Brink, James W. Young, Renier Brentjens, Nancy A. Kernan, Susan E. Prockop, Richard J. O'Reilly, Andromachi Scaradavou, Sophie Paczesny & 1 others Juliet N. Barker

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Abstract

While cord blood transplantation (CBT) is an effective therapy for hematologic malignancies, acute graft-versus-host disease (aGVHD) is a leading cause of transplant-related mortality (TRM). We investigated if biomarkers could predict aGVHD and TRM after day28 in CBT recipients. Day 28 samples from 113 CBT patients were analyzed. Suppressor of tumorigenicity 2 (ST2) was the only biomarker associated with grades II-IV and III-IV aGVHD and TRM. Day 180 grade III-IV aGVHD in patients with high ST2 levels was 30% (95% confidence interval [CI], 18-43) vs 13% (95% CI, 5-23) in patients with low levels (P=.024). The adverse effect of elevated ST2 was independent of HLA match. Moreover, high day 28 ST2 levels were associated with increased TRM with day 180 estimates of 23%(95% CI, 13-35) vs 5% (95% CI, 1-13) if levels were low (P = .001). GVHD was the most common cause of death in high ST2 patients. High concentrations of tumor necrosis factor receptor-1, interleukin-8, and regenerating islet-derived protein 3-α were also associated with TRM. Our results are consistent with those of adult donor allografts and warrant further prospective evaluationt of acilitate future therapeutic intervention to ameliorate severe aGVHD and further improve survival after CBT.

Original languageEnglish
Pages (from-to)199-205
Number of pages7
JournalBlood
Volume125
Issue number1
DOIs
StatePublished - Jan 1 2015

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Transplantation (surgical)
Transplants
Graft vs Host Disease
Fetal Blood
Grafts
Blood
Transplantation
Mortality
Confidence Intervals
Biomarkers
Tumor Necrosis Factor Receptors
Hematologic Neoplasms
Interleukin-8
Allografts
Cause of Death
Tissue Donors
Survival
Therapeutics

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Ponce, D. M., Hilden, P., Mumaw, C., Devlin, S. M., Lubin, M., Giralt, S., ... Barker, J. N. (2015). High day 28 ST2 levels predict for acute graft-versus-host disease and transplant-related mortality after cord blood transplantation. Blood, 125(1), 199-205. https://doi.org/10.1182/blood-2014-06-584789

High day 28 ST2 levels predict for acute graft-versus-host disease and transplant-related mortality after cord blood transplantation. / Ponce, Doris M.; Hilden, Patrick; Mumaw, Christen; Devlin, Sean M.; Lubin, Marissa; Giralt, Sergio; Goldberg, Jenna D.; Hanash, Alan; Hsu, Katharine; Jenq, Robert; Perales, Miguel Angel; Sauter, Craig; Van Den Brink, Marcel R M; Young, James W.; Brentjens, Renier; Kernan, Nancy A.; Prockop, Susan E.; O'Reilly, Richard J.; Scaradavou, Andromachi; Paczesny, Sophie; Barker, Juliet N.

In: Blood, Vol. 125, No. 1, 01.01.2015, p. 199-205.

Research output: Contribution to journalArticle

Ponce, DM, Hilden, P, Mumaw, C, Devlin, SM, Lubin, M, Giralt, S, Goldberg, JD, Hanash, A, Hsu, K, Jenq, R, Perales, MA, Sauter, C, Van Den Brink, MRM, Young, JW, Brentjens, R, Kernan, NA, Prockop, SE, O'Reilly, RJ, Scaradavou, A, Paczesny, S & Barker, JN 2015, 'High day 28 ST2 levels predict for acute graft-versus-host disease and transplant-related mortality after cord blood transplantation', Blood, vol. 125, no. 1, pp. 199-205. https://doi.org/10.1182/blood-2014-06-584789
Ponce, Doris M. ; Hilden, Patrick ; Mumaw, Christen ; Devlin, Sean M. ; Lubin, Marissa ; Giralt, Sergio ; Goldberg, Jenna D. ; Hanash, Alan ; Hsu, Katharine ; Jenq, Robert ; Perales, Miguel Angel ; Sauter, Craig ; Van Den Brink, Marcel R M ; Young, James W. ; Brentjens, Renier ; Kernan, Nancy A. ; Prockop, Susan E. ; O'Reilly, Richard J. ; Scaradavou, Andromachi ; Paczesny, Sophie ; Barker, Juliet N. / High day 28 ST2 levels predict for acute graft-versus-host disease and transplant-related mortality after cord blood transplantation. In: Blood. 2015 ; Vol. 125, No. 1. pp. 199-205.
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AU - Devlin, Sean M.

AU - Lubin, Marissa

AU - Giralt, Sergio

AU - Goldberg, Jenna D.

AU - Hanash, Alan

AU - Hsu, Katharine

AU - Jenq, Robert

AU - Perales, Miguel Angel

AU - Sauter, Craig

AU - Van Den Brink, Marcel R M

AU - Young, James W.

AU - Brentjens, Renier

AU - Kernan, Nancy A.

AU - Prockop, Susan E.

AU - O'Reilly, Richard J.

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AU - Paczesny, Sophie

AU - Barker, Juliet N.

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N2 - While cord blood transplantation (CBT) is an effective therapy for hematologic malignancies, acute graft-versus-host disease (aGVHD) is a leading cause of transplant-related mortality (TRM). We investigated if biomarkers could predict aGVHD and TRM after day28 in CBT recipients. Day 28 samples from 113 CBT patients were analyzed. Suppressor of tumorigenicity 2 (ST2) was the only biomarker associated with grades II-IV and III-IV aGVHD and TRM. Day 180 grade III-IV aGVHD in patients with high ST2 levels was 30% (95% confidence interval [CI], 18-43) vs 13% (95% CI, 5-23) in patients with low levels (P=.024). The adverse effect of elevated ST2 was independent of HLA match. Moreover, high day 28 ST2 levels were associated with increased TRM with day 180 estimates of 23%(95% CI, 13-35) vs 5% (95% CI, 1-13) if levels were low (P = .001). GVHD was the most common cause of death in high ST2 patients. High concentrations of tumor necrosis factor receptor-1, interleukin-8, and regenerating islet-derived protein 3-α were also associated with TRM. Our results are consistent with those of adult donor allografts and warrant further prospective evaluationt of acilitate future therapeutic intervention to ameliorate severe aGVHD and further improve survival after CBT.

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