486 Plasma-Derived Proteomic Biomarkers Have Prognostic Utility in Patients Treated with Post-Transplantation Cyclophosphamide As Single-Agent Graft-Versus-Host Disease Prophylaxis for HLA-Matched Allogeneic Bone Marrow Transplantation

Track: Poster Abstracts
Saturday, February 14, 2015, 6:45 PM-7:45 PM
Grand Hall CD (Manchester Grand Hyatt)
Christopher G. Kanakry, MD , Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD
Susan M. Perkins, PhD , School of Medicine, Indiana University, Indianapolis, IN
Etienne Daguindau, MD , School of Medicine, Indiana University, Indianapolis, IN
Ante Vulic, MD , Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD
Taylor Olmsted, MD , School of Medicine, Indiana University, Indianapolis, IN
Christen Mumaw, MS , School of Medicine, Indiana University, Indianapolis, IN
Shannon R. McCurdy, MD , Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD
Heather J. Symons, MD, MHS , Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD
Andrea M. Towlerton, BS , Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
Edus H. Warren, MD, PhD , Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
Paul V. O'Donnell, MD, PhD, FACP , Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
Sophie Paczesny, MD, PhD , School of Medicine, Indiana University, Indianapolis, IN
Leo Luznik, MD , Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD
Presentation recording not available for download or distribution as requested by the presenting author.
Introduction:  High-dose, post-transplantation cyclophosphamide  (PTCy) is effective as single-agent graft-versus-host disease (GVHD) prophylaxis after myeloablative conditioning (MAC) and human leukocyte antigen (HLA)-matched-related or –unrelated allogeneic bone marrow transplantation (alloBMT), producing grade III-IV acute GVHD and chronic GVHD rates of approximately 10-15% each.  However, it is unknown whether plasma-derived proteomic biomarkers previously established using other transplantation platforms are applicable to PTCy-treated patients.

Methods:  Plasma was obtained from the peripheral blood of 100 adult patients, 70 of whom received busulfan/fludarabine MAC and 30 of whom received busulfan/cyclophosphamide MAC, at month 1 and month 2-3 post-transplant.  Twelve healthy controls were used as a comparative group.   Plasma was analyzed using ELISA for interleukin-2 receptor alpha (IL-2rα), IL-6, tumor necrosis factor receptor-1 (TNFR-1), elafin, regenerating islet-derived 3-alpha (REG3α), suppression of tumorigenicity 2 (ST2), and chemokine (C-X-C motif) ligand 9 (CXCL9).

Results:  Plasma levels of 6 of the 7 putative biomarkers were significantly elevated (p<0.0001) in patients at 1 month post-transplant compared with healthy controls; only elafin levels were similar between patients and controls.  Plasma levels of IL-2rα (p=0.038), CXCL9 (p=0.0003), and IL-6 (p=0.032) at 1 month post-transplant were elevated in patients who would subsequently develop grade II-IV acute GVHD.  There also was a tendency of a relationship (p=0.06) between elevated elafin levels at 1 month post-transplant and grade II-IV acute GVHD development.  None of the 7 biomarkers at post-transplant month 1 was prognostic of chronic GVHD development.  However, elevated REG3α levels at month 2-3 were prognostic of the subsequent development of chronic GVHD (p=0.027).  Elevations in 4 of the 7 biomarkers (IL-2rα, p=0.014; IL-6, p=0.024; TNFR-1, p=0.033; and ST-2, p=0.0032) were predictive of non-relapse mortality (NRM).  Levels of the 7 biomarkers at month 1 were not predictive of permanent cessation of immunosuppressive therapy for GVHD by 1 year post-transplant.

Conclusion:  Levels of all 7 tested biomarkers at month 1 or month 2-3 post-transplant were prognostic for the occurrence of acute GVHD, chronic GVHD, and/or NRM in patients treated with PTCy as single-agent GVHD prophylaxis after MAC and HLA-matched-related or –unrelated alloBMT.  Testing of these biomarkers at earlier post-transplant time periods or at patient-specific time points such as initiation of treatment for GVHD may have added clinical utility in the care of PTCy-treated patients.

Disclosures:
Nothing To Disclose
See more of: Poster Session 2: GVH/GVL
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