[en] BACKGROUND: It is unknown whether the duration of systemic immunosuppressive treatment after allogeneic nonmyeloablative hematopoietic cell transplantation (HCT) might influence the incidence, severity, timing, and/or corticosteroid-responsiveness of graft-versus-host disease (GVHD). METHODS: We retrospectively analyzed outcomes among 185 patients with hematologic malignancies who were given grafts from HLA-matched related donors following conditioning with 2 Gy total body irradiation alone or in combination with fludarabine between December 1998 and March 2003. Postgrafting immunosuppression consisted of mycophenolate mofetil (days 0-27) in combination with 3 different cyclosporine (CSP) regimens: taper from (A) days 35 to 56 (n=107), (B) days 56 to 77 (n=35), and (C) days 56 to 180 (n=43). RESULTS: The overall incidences of grades II-IV and III-IV acute GVHD, and extensive chronic GVHD were 52%, 13%, and 56%, respectively. The duration of CSP prophylaxis did not significantly influence the overall rate of acute GVHD (grade II-IV), extensive chronic GVHD, or non-relapse mortality. However, prolonged administration of CSP (group C) was associated with a significantly decreased hazard of grades III-IV acute GVHD (HR 0.2, 95% CI [0.04, 0.9]) and with an increased likelihood of discontinuing all systemic immunosuppression (HR 2.4, 95% CI [1.1, 5.2]) when compared to the shortest course of CSP (group A). CONCLUSION: Longer CSP duration decreased the risk of severe GVHD and increased the likelihood of discontinuing all systemic immunosuppression after nonmyeloablative HCT with HLA-matched related grafts.
Disciplines :
Hematology
Author, co-author :
Burroughs, Lauri
Mielcarek, Marco
Leisenring, Wendy
Sandmaier, Brenda M
Maloney, David G
Baron, Frédéric ; Université de Liège - ULiège > Département des sciences cliniques > GIGA-R : Hématologie - Département des sciences cliniques
Martin, Paul ; Université de Liège - ULiège > Département des sciences de la santé publique > Médecine légale - Criminalistique
Flowers, Mary E D
Forman, Stephen J
Chauncey, Thomas R
Bruno, Benedetto
Storb, Rainer
Language :
English
Title :
Extending postgrafting cyclosporine decreases the risk of severe graft-versus-host disease after nonmyeloablative hematopoietic cell transplantation
Publication date :
2006
Journal title :
Transplantation
ISSN :
0041-1337
eISSN :
1534-6080
Publisher :
Lippincott Williams & Wilkins, Hagerstown, United States - Maryland
Sorror ML, Maris MB, Storer B, et al. Comparing morbidity and mortality of HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative and myeloablative conditioning: influence of pretransplant comorbidities. Blood 2004; 104: 961-968.
Diaconescu R, Flowers CR, Storer B, et al. Morbidity and mortality with nonmyeloablative compared to myeloablative conditioning before hematopoietic cell transplantation from HLA matched related donors. Blood 2004; 104: 1550-1558.
Mielcarek M, Martin PJ, Leisenring W, et al. Graft-versus-host disease after nonmyeloablative versus conventional hematopoietic stem cell transplantation. Blood 2003; 102: 756-762.
Ramsay NKC, Kersey JH, Robison LL, et al. A randomized study of the prevention of acute graft-versus-host disease. N Engl J Med 1982; 306: 392-397.
Storb R, Deeg HJ, Pepe M, et al. Graft-versus-host disease prevention by methotrexate combined with cyclosporin compared to methotrexate alone in patients given marrow grafts for severe aplastic anaemia: Long-term follow-up of a controlled trial. Br J Haematol 1989; 72: 567-572.
Storb R, Deeg HJ, Whitehead J, et al. Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia. N Engl J Med 1986; 314: 729-735.
Storb R, Deeg HJ, Pepe M, et al. Methotrexate and cyclosporine versus cyclosporine alone for prophylaxis of graft-versus-host disease in patients given HLA-identical marrow grafts for leukemia: Long-term follow-up of a controlled trial. Blood 1989; 73: 1729-1734.
Forman SJ, Blume KG, Krance RA, et al. A prospective randomized study of acute graft-v-host disease in 107 patients with leukemia: Methotrexate/ prednisone v cyclosporine A/prednisone. Transplant Proc 1987; 19: 2605-2607.
Santos GW, Tutschka PJ, Brookmeyer R, et al. Cyclosporine plus methylprednisolone versus cyclophosphamide plus methylprednisolone as prophylaxis for graft-versus-host disease: A randomized double-blind study in patients undergoing allogeneic marrow transplantation. Clin Transplant 1987; 1: 21-28.
Storb R, Pepe M, Anasetti C, et al. What role for prednisone in prevention of acute graft-versus-host disease in patients undergoing marrow transplants? Blood 1990; 76: 1037-1045.
Chao NJ, Schmidt GM, Niland JC, et al. Cyclosporine, methotrexate, and prednisone compared with cyclosporine and prednisone for prophylaxis of acute graft-versus-host disease. N Engl J Med 1993; 329: 1225-1230.
Deeg HJ, Lin D, Leisenring W, et al. Cyclosporine or cyclosporine plus methylprednisolone for prophylaxis of graft-versus-host disease: a prospective, randomized trial. Blood 1997; 89: 3880-3887.
Ratanatharathorn V, Nash RA, Przepiorka D, et al. Phase III study comparing methotrexate and tacrolimus (Prograf, FK506) with methotrexate and cyclosporine for graft-versus-host-disease prophylaxis after HLA-identical sibling bone marrow transplantation. Blood 1998; 92: 2303-2314.
Ruutu T, Volin L, Parkkali T, et al. Cyclosporine, methotrexate, and methylprednisolone compared with cyclosporine and methotrexate for the prevention of graft-versus-host disease in bone marrow transplantation from HLA-identical sibling donor: a prospective randomized study. Blood 2000; 96: 2391-2398.
Locatelli F, Bruno B, Zecca M, et al. Cyclosporin A and short-term methotrexate versus cyclosporin A as graft versus host disease prophylaxis in patients with severe aplastic anemia given allogeneic bone marrow transplantation from an HLA-identical sibling: results of a GITMO/EBMT randomized trial. Blood 2000; 96: 1690-1697.
Nash RA, Antin JH, Karanes C, et al. Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors. Blood 2000; 96: 2062-2068.
Srinivasan R, Geller N, Chakrabarti S, et al. Evaluation of three different cyclosporine-based graft versus host disease (GVHD) prophylaxis regimens following nonmyeloablative hematopoietic stem cell transplantation (NST). Blood 2004; 104: 349a.
Storb R, Yu C, Wagner JL, et al. Stable mixed hematopoietic chimerism in DLA-identical littermate dogs given sublethal total body irradiation before and pharmacological immunosuppression after marrow transplantation. Blood 1997; 89: 3048-3054.
Maris MB, Niederwieser D, Sandmaier BM, et al. HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies. Blood 2003; 102: 2021-2030.
Niederwieser D, Maris M, Shizuru JA, et al. Low-dose total body irradiation (TBI) and fludarabine followed by hematopoietic cell transplantation (HCT) from HLA-matched or mismatched unrelated donors and postgrafting immunosuppression with cyclosporine and mycophenolate mofetil (MMF) can induce durable complete chimerism and sustained remissions in patients with hematological diseases. Blood 2003; 101: 1620-1629.
McSweeney PA, Niederwieser D, Shizuru JA, et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood 2001; 97: 3390-3400.
Sandmaier BM, Maloney DG, Gooley TA, et al. Low dose TBI conditioning for hematopoietic stem cell transplants (HSCT) from HLA-matched related donors for patients with hematologic malignancies: influence of fludarabine or cytoreductive autografts on outcome. Blood 2002; 100: 145a.
Sandmaier BM, Maris M, Maloney DG, et al. Low-dose total body irradiation (TBI) conditioning for hematopoietic cell transplants (HCT) from HLA-matched related (MRD) and unrelated (URD) donors for patients with hematologic malignancies: a five-year experience. Blood 2003; 102: 78a.
Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus conference on acute GVHD grading. Bone Marrow Transplant 1995; 15: 825-828.
Sullivan KM, Agura E, Anasetti C, et al. Chronic graft-versus-host disease and other late complications of bone marrow transplantation. Semin Hematol 1991; 28: 250-259.
Nash RA, Pepe MS, Storb R, et al. Acute graft-versus-host disease: analysis of risk factors after allogeneic marrow transplantation and prophylaxis with cyclosporine and methotrexate. Blood 1992; 80: 1838-1845.
Weiden PL, Flournoy N, Thomas ED, et al. Antileukemic effect of graft-versus-host disease in human recipients of allogeneic-marrow grafts. N Engl J Med 1979; 300: 1068-1073.
Storb R, Prentice RL, Buckner CD, et al. Graft-versus-host disease and survival in patients with aplastic anemia treated by marrow grafts from HLA-identical siblings. Beneficial effect of a protective environment. N Engl J Med 1983; 308: 302-307.
Glucksberg H, Storb R, Fefer A, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 1974; 18: 295-304.
Baron F, Maris MB, Sandmaier BM, et al. Graft-versus-tumor effects after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning. J Clin Oncol 2005; 23: 1993-2003.
Storb R, Leisenring W, Anasetti C, et al. Methotrexate and cyclosporine for graft-vs.-host disease prevention: what length of therapy with cyclosporine? Biol Blood and Marrow Transplantation 1997; 3: 194-201.
Kansu E, Gooley T, Flowers MED, et al. Administration of cyclosporine for 24 months compared with 6 months for prevention of chronic graft-versus-host disease: a prospective randomized clinical trial (Brief Report). Blood 2001; 98: 3868-3870.
Bacigalupo A, Maiolino A, Van Lint MT, et al. Cyclosporin A and chronic graft versus host disease. Bone Marrow Transplant 1990; 6: 341-344.
Mengarelli A, Iori AP, Romano A, et al. One-year cyclosporine prophylaxis reduces the risk of developing extensive chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplantation. Haematologica 2003; 88: 315-323.
