ST2 as a marker for risk of therapy-resistant graft-versus-host disease and death

Mark T. Vander Lugt, Thomas M. Braun, Samir Hanash, Jerome Ritz, Vincent T. Ho, Joseph H. Antin, Qing Zhang, Chee Hong Wong, Hong Wang, Alice Chin, Aurélie Gomez, Andrew C. Harris, John E. Levine, Sung W. Choi, Daniel Couriel, Pavan Reddy, James L M Ferrara, Sophie Paczesny

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Abstract

BACKGROUND: No plasma biomarkers are associated with the response of acute graft-versus-host disease (GVHD) to therapy after allogeneic hematopoietic stem-cell transplantation. METHODS: We compared 12 biomarkers in plasma obtained a median of 16 days after therapy initiation from 10 patients with a complete response by day 28 after therapy initiation and in plasma obtained from 10 patients with progressive GVHD during therapy. The lead biomarker, suppression of tumorigenicity 2 (ST2), was measured at the beginning of treatment for GVHD in plasma from 381 patients and during the first month after transplantation in three independent sets totaling 673 patients to determine the association of this biomarker with treatment-resistant GVHD and 6-month mortality after treatment or transplantation. RESULTS: Of the 12 markers, ST2 had the most significant association with resistance to GVHD therapy and subsequent death without relapse. As compared with patients with low ST2 values at therapy initiation, patients with high ST2 values were 2.3 times as likely to have treatment-resistant GVHD (95% confidence interval [CI], 1.5 to 3.6) and 3.7 times as likely to die within 6 months after therapy (95% CI, 2.3 to 5.9). Patients with low ST2 values had lower mortality without relapse than patients with high ST2 values, regardless of the GVHD grade (11% vs. 31% among patients with grade I or II GVHD and 14% vs. 67% among patients with grade III or IV GVHD, P

Original languageEnglish (US)
Pages (from-to)529-539
Number of pages11
JournalNew England Journal of Medicine
Volume369
Issue number6
DOIs
StatePublished - 2013
Externally publishedYes

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Graft vs Host Disease
Biomarkers
Therapeutics
Transplantation
Confidence Intervals
Recurrence
Mortality
Hematopoietic Stem Cell Transplantation

ASJC Scopus subject areas

  • Medicine(all)

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ST2 as a marker for risk of therapy-resistant graft-versus-host disease and death. / Vander Lugt, Mark T.; Braun, Thomas M.; Hanash, Samir; Ritz, Jerome; Ho, Vincent T.; Antin, Joseph H.; Zhang, Qing; Wong, Chee Hong; Wang, Hong; Chin, Alice; Gomez, Aurélie; Harris, Andrew C.; Levine, John E.; Choi, Sung W.; Couriel, Daniel; Reddy, Pavan; Ferrara, James L M; Paczesny, Sophie.

In: New England Journal of Medicine, Vol. 369, No. 6, 2013, p. 529-539.

Research output: Contribution to journalArticle

Vander Lugt, MT, Braun, TM, Hanash, S, Ritz, J, Ho, VT, Antin, JH, Zhang, Q, Wong, CH, Wang, H, Chin, A, Gomez, A, Harris, AC, Levine, JE, Choi, SW, Couriel, D, Reddy, P, Ferrara, JLM & Paczesny, S 2013, 'ST2 as a marker for risk of therapy-resistant graft-versus-host disease and death', New England Journal of Medicine, vol. 369, no. 6, pp. 529-539. https://doi.org/10.1056/NEJMoa1213299
Vander Lugt, Mark T. ; Braun, Thomas M. ; Hanash, Samir ; Ritz, Jerome ; Ho, Vincent T. ; Antin, Joseph H. ; Zhang, Qing ; Wong, Chee Hong ; Wang, Hong ; Chin, Alice ; Gomez, Aurélie ; Harris, Andrew C. ; Levine, John E. ; Choi, Sung W. ; Couriel, Daniel ; Reddy, Pavan ; Ferrara, James L M ; Paczesny, Sophie. / ST2 as a marker for risk of therapy-resistant graft-versus-host disease and death. In: New England Journal of Medicine. 2013 ; Vol. 369, No. 6. pp. 529-539.
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abstract = "BACKGROUND: No plasma biomarkers are associated with the response of acute graft-versus-host disease (GVHD) to therapy after allogeneic hematopoietic stem-cell transplantation. METHODS: We compared 12 biomarkers in plasma obtained a median of 16 days after therapy initiation from 10 patients with a complete response by day 28 after therapy initiation and in plasma obtained from 10 patients with progressive GVHD during therapy. The lead biomarker, suppression of tumorigenicity 2 (ST2), was measured at the beginning of treatment for GVHD in plasma from 381 patients and during the first month after transplantation in three independent sets totaling 673 patients to determine the association of this biomarker with treatment-resistant GVHD and 6-month mortality after treatment or transplantation. RESULTS: Of the 12 markers, ST2 had the most significant association with resistance to GVHD therapy and subsequent death without relapse. As compared with patients with low ST2 values at therapy initiation, patients with high ST2 values were 2.3 times as likely to have treatment-resistant GVHD (95{\%} confidence interval [CI], 1.5 to 3.6) and 3.7 times as likely to die within 6 months after therapy (95{\%} CI, 2.3 to 5.9). Patients with low ST2 values had lower mortality without relapse than patients with high ST2 values, regardless of the GVHD grade (11{\%} vs. 31{\%} among patients with grade I or II GVHD and 14{\%} vs. 67{\%} among patients with grade III or IV GVHD, P",
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AU - Vander Lugt, Mark T.

AU - Braun, Thomas M.

AU - Hanash, Samir

AU - Ritz, Jerome

AU - Ho, Vincent T.

AU - Antin, Joseph H.

AU - Zhang, Qing

AU - Wong, Chee Hong

AU - Wang, Hong

AU - Chin, Alice

AU - Gomez, Aurélie

AU - Harris, Andrew C.

AU - Levine, John E.

AU - Choi, Sung W.

AU - Couriel, Daniel

AU - Reddy, Pavan

AU - Ferrara, James L M

AU - Paczesny, Sophie

PY - 2013

Y1 - 2013

N2 - BACKGROUND: No plasma biomarkers are associated with the response of acute graft-versus-host disease (GVHD) to therapy after allogeneic hematopoietic stem-cell transplantation. METHODS: We compared 12 biomarkers in plasma obtained a median of 16 days after therapy initiation from 10 patients with a complete response by day 28 after therapy initiation and in plasma obtained from 10 patients with progressive GVHD during therapy. The lead biomarker, suppression of tumorigenicity 2 (ST2), was measured at the beginning of treatment for GVHD in plasma from 381 patients and during the first month after transplantation in three independent sets totaling 673 patients to determine the association of this biomarker with treatment-resistant GVHD and 6-month mortality after treatment or transplantation. RESULTS: Of the 12 markers, ST2 had the most significant association with resistance to GVHD therapy and subsequent death without relapse. As compared with patients with low ST2 values at therapy initiation, patients with high ST2 values were 2.3 times as likely to have treatment-resistant GVHD (95% confidence interval [CI], 1.5 to 3.6) and 3.7 times as likely to die within 6 months after therapy (95% CI, 2.3 to 5.9). Patients with low ST2 values had lower mortality without relapse than patients with high ST2 values, regardless of the GVHD grade (11% vs. 31% among patients with grade I or II GVHD and 14% vs. 67% among patients with grade III or IV GVHD, P

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