ST2 as a marker for risk of therapy-resistant graft-versus-host disease and death.
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<0.001 for both comparisons). Plasma ST2 values at day 14 after transplantation were associated with 6-month mortality without relapse, regardless of the intensity of the conditioning regimen.


CONCLUSIONS
ST2 levels measured at the initiation of therapy for GVHD and during the first month after transplantation improved risk stratification for treatment-resistant GVHD and death without relapse after transplantation. (Funded by the National Institutes of Health.)
Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
Mark T
MT
Vander Lugt
Thomas M
TM
Braun
Samir
S
Hanash
Jerome
J
Ritz
Vincent T
VT
Ho
Joseph H
JH
Antin
Qing
Q
Zhang
Chee-Hong
CH
Wong
Hong
H
Wang
Alice
A
Chin
Aurélie
A
Gomez
Andrew C
AC
Harris
John E
JE
Levine
Sung W
SW
Choi
Daniel
D
Couriel
Pavan
P
Reddy
James L M
JL
Ferrara
Sophie
S
Paczesny
D015415:Biomarkers / Q000097:blood; D006086:Graft vs Host Disease / Q000097:blood* / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000097:blood*; D012008:Recurrence; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D014184:Transplantation, Homologous
D015415:Biomarkers; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D011956:Receptors, Cell Surface