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High levels of ST2 associated with treatment resistance, death in GVHD
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Improvements in risk stratification to predict treatment-resistant acute graft-versus-host disease and mortality without relapse were observed when suppression of tumorigenicity 2 levels were measured at therapy initiation and within the first month after stem cell transplantation, according to recent study findings.
“The ability to identify high-risk patients with the use of suppression of tumorigenicity 2 soon after transplantation, before the development of acute graft-versus-host disease, may permit more stringent monitoring and preemptive interventions,” Sophie Paczesny, MD, PhD, of the department of pediatrics and the bone marrow and stem cell transplantation program at Indiana University Melvin and Bren Simon Cancer Center and Wells Center for Pediatric Research, and colleagues wrote.
Sophie Paczesny
No studies to date have identified a plasma biomarker associated with response of acute graft-versus-host disease (GVHD) to therapy after allogeneic hematopoietic stem-cell transplantation.
In the current study, Paczesny and colleagues compared 12 biomarkers in plasma obtained from two sets of patients. They obtained the first set about 16 days after initiation of therapy from 10 patients who achieved a complete response by day 28. They obtained the second set from 10 patients with progressive GVHD during therapy.
Researchers then measured the suppression of tumorigenicity 2 (ST2) at the beginning of treatment for GVHD in plasma from 381 patients and again during the first month after transplantation in three independent sets to determine the association of this biomarker with treatment-resistant GVHD and 6-month mortality after treatment or transplantation.
Patients with high levels of ST2 were 2.3 times more likely to have treatment-resistant GVHD (95% CI, 1.5-3.6) and 3.7 times more likely to die within 6 months after therapy (95% CI, 2.3 to 5.9) when compared with patients with low levels of ST2.
In addition, regardless of GVHD grade, those with lower levels of ST2 had a decreased incidence for mortality vs. those with higher levels of ST2 (11% vs. 31% among patients with grade 1 or 2 GVHD, and 14% vs. 67% among patients with grade 3 or 4 GVHD; P<.001 for both).
Plasma ST2 levels at 2 weeks after transplantation were associated with 6-month mortality without relapse, regardless of the intensity of the conditioning regimen, according to the researchers.
“This discovery will enable doctors to accurately predict the risk of deadly graft-versus-host disease in stem cell transplant recipients and personalize their treatment,” Paczesny told HemOnc Today. “For example, this blood test, which is currently available to clinicians, will make informed treatment possible as the clinicians will now be able to adjust therapy to the degree of risk rather than treating every patient the same way.”
Sophie Paczesny, MD, PhD, can be reached at sophpacz@iupui.edu.
Disclosure: The study was funded by the NIH.
Perspective
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Corey Cutler, MD, MPH, FRCP
This study provides us one of the first measurable prognostic markers that we can use to stratify patients at the onset of GVHD. By measuring ST2 at the onset of GVHD, we can determine which patients are likely to respond to therapy, and we can tailor our approach for those whose ST2 levels suggest a higher likelihood of treatment failure. This might be the beginning of personalized therapy for acute GVHD. Patients in whom ST2 levels suggest lack of response to corticosteroid therapy might be offered intensified immunosuppressive regimens, with a goal of increasing response rates, and hopefully reducing GVHD-associated mortality. Although encouraging, these data do need to be verified in a prospective analysis. More importantly, we must demonstrate that tailoring therapy based on ST2 level at the onset of GVHD is associated with an improvement in outcome.
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