Article

Acute graft-versus-host disease biomarkers measured during therapy can predict treatment outcomes: a Blood and Marrow Transplant Clinical Trials Network study.

University of Michigan Blood and Marrow Transplant Program, Ann Arbor, USA.
Blood (Impact Factor: 9.78). 03/2012; 119(16):3854-60. DOI: 10.1182/blood-2012-01-403063
Source: PubMed

ABSTRACT Acute graft-versus-host disease (GVHD) is the primary limitation of allogeneic hematopoietic cell transplantation, and once it develops, there are no reliable diagnostic tests to predict treatment outcomes. We hypothesized that 6 previously validated diagnostic biomarkers of GVHD (IL-2 receptor-α; tumor necrosis factor receptor-1; hepatocyte growth factor; IL-8; elafin, a skin-specific marker; and regenerating islet-derived 3-α, a gastrointestinal tract-specific marker) could discriminate between therapy responsive and nonresponsive patients and predict survival in patients receiving GVHD therapy. We measured GVHD biomarker concentrations from samples prospectively obtained at the initiation of treatment, day 14, and day 28, on a multicenter, randomized, 4-arm phase 2 clinical trial for newly diagnosed acute GVHD. We found that at each of 3 time points, GVHD onset, 2 weeks into treatment, and 4 weeks into treatment, a 6-protein biomarker panel predicted for the important clinical outcomes of day 28 posttherapy nonresponse and mortality at day 180 from onset. GVHD biomarker panels can be used for early identification of patients at high or low risk for treatment nonresponsiveness or death, and they may provide opportunities for early intervention and improved survival after hematopoietic cell transplantation. The study was registered in clinicaltrials.gov as NCT00224874.

1 Bookmark
 · 
120 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The initial evaluation of patients with suspected deep vein thrombosis includes the use of biomarkers reflecting activation of the coagulation system. However, the thromboembolic process and neighboring inflammatory responses also affect endothelial cells, and endothelial cell markers may therefore be altered by the disease. In the present population-based single-center study, we investigated the plasma levels of the endothelium-specific biomarkers soluble E-selectin and endocan in a consecutive and unselected group of 120 patients admitted to hospital for suspected deep vein thrombosis. Blood samples were collected when patients arrived at the hospital. DVT patients showed evidence for an acute phase reaction with increased serum C-reactive protein levels, but this was similar to many other patients admitted with suspected but not verified thrombosis. Plasma endocan and E-selectin levels did not differ between patients with thrombosis, healthy controls and the patients without verified thrombosis (i.e. patients with other causes of their symptoms, including various inflammatory and non-inflammatory conditions). However, the combined use of endothelial biomarkers, C-reactive protein and D-dimer could be used to identify patient subsets with different frequencies of venous thrombosis. Thus, analysis of plasma biomarker profiles including endothelial cell markers may be helpful in the initial evaluation of patients with deep vein thrombosis.
    SpringerPlus 01/2014; 3:571.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Five candidate plasma biomarkers (ST2, REG3α, elafin, TNFR1, sIL2Rα) were measured at specific time-points following cyclophosphamide/fludarabine-based nonmyeloablative allotransplantation (NMAT) in patients who did or did not develop acute graft-versus-host-disease (aGVHD). Plasma samples from 34 patients were analyzed at days +7, +14, +21 and +30. At a median follow-up of 358 days, 17 patients had experienced aGVHD with a median time to onset of day +36. Risk of aGVHD was associated with elevated plasma ST2 concentrations at day +7 (c-stat=0.72, p=0.03), day +14 (c-stat=0.74, p=0.04), and day +21 (c-stat=0.75, p=0.02); elevated plasma REG3α concentrations at day +14 (c-stat=0.73, p=0.03), day +21 (c-stat=0.76, p=0.01) and day +30 (c-stat=0.73, p=0.03); and elevated elafin at day +14 (c-stat=0.71, p=0.04). Plasma concentrations of TNFR1 and sIL2Rα were not associated with aGVHD risk at any of the time-points studied. This study identified ST2, REG3α and elafin as prognostic biomarkers to evaluate risk of aGVHD following Cy/Flu-based NMAT. These results need to be confirmed in an independent validation cohort.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 07/2014; 20(11). · 3.15 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Biomarkers have the potential to improve diagnosis and prognosis, facilitate targeted treatment, and reduce health care costs. Thus, there is great hope that biomarkers will be integrated in all clinical decisions in the near future. A decade ago, the biomarker field was launched with great enthusiasm because mass spectrometry revealed that blood contains a rich library of candidate biomarkers. However, biomarker research has not yet delivered on its promise due to several limitations: (i) improper sample handling and tracking as well as limited sample availability in the pediatric population, (ii) omission of appropriate controls in original study designs, (iii) lability and low abundance of interesting biomarkers in blood, and (iv) the inability to mechanistically tie biomarker presence to disease biology. These limitations as well as successful strategies to overcome them are discussed in this review. Several advances in biomarker discovery and validation have been made in hematopoietic stem cell transplantation, the current most effective tumor immunotherapy, and these could serve as examples for other conditions. This review provides fresh optimism that biomarkers clinically relevant in pediatrics are closer to being realized based on: (i) a uniform protocol for low-volume blood collection and preservation, (ii) inclusion of well-controlled independent cohorts, (iii) novel technologies and instrumentation with low analytical sensitivity, and (iv) integrated animal models for exploring potential biomarkers and targeted therapies.This article is protected by copyright. All rights reserved
    PROTEOMICS - CLINICAL APPLICATIONS 09/2014; 8(11-12). · 1.81 Impact Factor

Full-text

Download
28 Downloads
Available from
May 22, 2014