A biomarker-guided,prospective, phase 2 trial of pre-emptive graft-versus-host disease therapy using anti-thymocyte globulin |
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| Affiliation: | 1. Cumming School of Medicine, University of Calgary, Calgary, Canada;2. Alberta Health Services, Calgary, Canada;3. Alberta Precision Laboratories, Calgary, Canada;1. Medical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, Burn and Combined Injury, Third Military Medical University (Army Medical University), Chongqing, China;2. Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, California, USA;3. Department of Cell Biology, College of Basic Medicine, Third Military Medical University (Army Medical University), Chongqing, China;1. Division of Hematology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada;2. Division of Rheumatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada;3. Division of Dermatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada;4. Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada;6. Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada;1. Division of Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Center for Definitive and Curative Medicine, Stanford School of Medicine, Stanford, California, USA;2. Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, California, USA |
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| Abstract: | Background aimsIntensified immunosuppressive prophylaxis for graft-versus-host disease (GVHD) may be toxic and therefore warranted only in patients at high risk of developing GVHD. In patients who underwent allogeneic hematopoietic cell transplant at the authors’ center, high serum soluble IL-2 receptor alpha (sIL-2Rα) and low IL-15 levels on day 7 post-transplant were found to predict a high risk of developing clinically significant GVHD (sGVHD), defined as grade 2–4 acute GVHD or moderate to severe chronic GVHD.MethodsThis was a prospective, phase 2 trial in which high-risk patients (serum sIL-2Rα >4500 ng/L or IL-15 <31 ng/L) received rabbit anti-thymocyte globulin (ATG) 3 mg/kg on day 8 post-transplant. Controls consisted of patients who had their sIL-2Rα/IL-15 levels measured but did not participate in the trial. A total of 68 trial patients and 143 controls were accrued to this study. The primary endpoint was incidence of sGVHD.ResultsThere was a reduction in sGVHD in high-risk trial patients (received day 8 ATG) compared with high-risk controls (did not receive day 8 ATG) (sub-hazard ratio [SHR] = 0.48, P < 0.05). There was no significant difference between the groups in overall survival or relapse; however, there was a greater incidence of non-GVHD-associated non-relapse mortality in high-risk trial patients (SHR = 3.73, P < 0.05), mostly related to infections. This may be due in part to the biomarkers ineffectively stratifying GVHD risk.ConclusionsPre-emptive ATG therapy is both feasible and effective at reducing sGVHD without increasing relapse. Further mitigation strategies are needed to reduce the risk of infection associated with intensified GVHD prophylaxis. This study was registered at ClinicalTrials.gov (NCT01994824). |
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