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Published on: March 17, 2020
Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis
Javier Bolaños-Meade1, Mehdi Hamadani1, Juan Wu1
1From the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, and the Department of Oncology, Johns Hopkins University School of Medicine, Baltimore (J.B.-M., R.J.J.), Emmes, Rockville (J.W., K.A.), and the Division of Blood Diseases and Resources (N.L.D.) and the Office of Biostatistics Research (E.L.), National Heart, Lung, and Blood Institute, Bethesda - all in Maryland; the Blood and Marrow Transplant Program and Cellular Therapy Program (M.H.) and the Center for International Blood and Marrow Transplant Research (CIBMTR), Department of Medicine (M.H., M.M.H.), the CIBMTR Division of Biostatistics, Institute for Health and Equity (M.J.M.), and the Division of Hematology and Oncology, Department of Medicine (L.R.), Medical College of Wisconsin, Milwaukee, and the Division of Hematology and Oncology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison (A.C.H.) - both in Wisconsin; the Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University School of Medicine, Stanford (A.R.R.), the Department of Hematology and Hematopoietic Cell Transplantation, City of Hope (M.M.A.M.), and the Department of Pharmacy, City of Hope National Medical Center (J.M.Y.), Duarte, and the Division of Hematology, Departments of Medicine and Genetics, Stanford University, Palo Alto (A.S.B.) - all in California; the Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer and Research Institute, Tampa, FL (H.E.); the Department of Hematology and Oncology, Dana-Farber Cancer Institute (M.G., L.S.K.), and the Department of Pediatrics, Harvard Medical School, and the Division of Pediatric Hematology and Oncology, Boston Children's Hospital (L.S.K.) - all in Boston; the Ohio State University Comprehensive Cancer Center, Columbus (K.T.L., Y.A.E.); Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, and the Department of Medicine, Weill Cornell Medical College (B.C.S., M.-A.P.), and the Blood and Marrow Transplantation Program, Columbia University Irving Medical Center (R.R.) - all in New York; the Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis (N.E.J., S.G.H.); the Division of Hematology and Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia (A.W.L.); the Blood and Marrow Transplant Program at Northside Hospital, Atlanta (M.S.); the Department of Stem Cell Transplantation and Cellular Therapy, the University of Texas M.D. Anderson Cancer Center, Houston (A.M.A.); the Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham (O.H.J.); and the Division of Hematology-Oncology and Palliative Care, Department of Medicine, Virginia Commonwealth University, Richmond (W.C.).
A new prophylaxis regimen of cyclophosphamide, tacrolimus, and mycophenolate mofetil significantly improved graft-versus-host disease (GVHD)-free, relapse-free survival after allogeneic stem-cell transplantation compared to the standard tacrolimus and methotrexate regimen.
Area of Science:
- Hematology
- Immunology
- Transplantation Medicine
Background:
- Graft-versus-host disease (GVHD) prophylaxis after allogeneic hematopoietic stem-cell transplantation (HSCT) traditionally uses calcineurin inhibitors plus methotrexate.
- A phase 2 study suggested a post-transplantation regimen of cyclophosphamide, tacrolimus, and mycophenolate mofetil may be superior.
Purpose of the Study:
- To compare the efficacy of cyclophosphamide-tacrolimus-mycophenolate mofetil versus tacrolimus-methotrexate for GVHD prophylaxis in adults undergoing HSCT.
Main Methods:
- A phase 3 trial randomized 431 adults with hematologic cancers to receive either experimental (cyclophosphamide-tacrolimus-mycophenolate mofetil) or standard (tacrolimus-methotrexate) prophylaxis.
- Patients underwent HSCT from HLA-matched related or 7/8 mismatched unrelated donors after reduced-intensity conditioning.
- The primary endpoint was GVHD-free, relapse-free survival at 1 year.
Main Results:
- GVHD-free, relapse-free survival at 1 year was significantly higher in the experimental group (52.7%) compared to the standard group (34.9%).
- The experimental regimen showed a reduced hazard for acute or chronic GVHD, relapse, or death (HR, 0.64; P=0.001).
- Patients receiving experimental prophylaxis experienced less severe GVHD and higher rates of immunosuppression-free survival.
Conclusions:
- Cyclophosphamide-tacrolimus-mycophenolate mofetil is a superior prophylaxis strategy for GVHD in patients undergoing allogeneic HSCT with reduced-intensity conditioning.
- This regimen significantly improves GVHD-free, relapse-free survival compared to standard tacrolimus-methotrexate.
- The findings support the use of this novel regimen in clinical practice for HSCT recipients.
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