Summary
Fifty-seven patients undergoing bone marrow transplantation were randomly assigned to receive either cyclosporin A (CsA, n=26) or methotrexate, followed by rescue with folinic acid (MTX + FA, n=31) as prophylaxis for graft-versus-host disease (GVHD). All patients but one receiving CsA had evidence of sustained engraftment, and there was no difference between the two groups on the day in which marrow engraftment was documented. Oropharyngeal mucositis was of similar incidence and severity in the two groups. In contrast, patients receiving CsA showed higher renal and hepatic toxicity rates than those treated with MTX + FA. Severe-to-moderate acute GVHD (grades II–IV) was documented in 12 patients receiving CsA and in 12 treated with MTX + FA. The cumulative incidence of this complication was similar in both groups (46.1% and 38.7%). Similarly, there was no difference in the incidence of chronic GVHD. The leukemic relapse rates were also comparable, as well as the estimated probability of survival, which was 55% in patients treated with MTX + FA and 41% in those who were given CsA. We conclude that MTX + FA is as effective as CsA in the prevention of GVHD, with the additional advantage of reduced renal and hepatic toxicities.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Atkinson K, Biggs JC, Ting A, Concannon AJ, Dodds AJ, Pun A (1982) Cyclosporin A is associated with faster engraftment and less mucositis than methotrexate after allogenic bone marrow transplantation. Br J Haematol 53: 265–270
Bortin MM (1983) Pathogenesis of interstitial pneumonitis following allogenic bone marrow transplantation for acute leukemia. In: Gale RP (ed) Recent advances in bone marrow/transplantation. Allan R. Liss, New York, pp 445–460
Deeg HJ, Torok-Storb B, Storb R, Weiden PL (1980) Effect of cyclosporin A (CyA) on marrow engraftment in vivo and on hematopoiesis in vitro. Exp Hematol 8: 78 (abstract 138)
Deeg HJ, Storb R, Thomas ED, Kennedy MS, Fluornoy N, Buckner CD, Clift R, Doney K, Sale G, Sanders J, Witherspoon R (1983) Marrow transplantation for acute nonlymphoblastic leukemia in first remission: preliminary results of a randomized trial comparing cyclosporin and methotrexate for the prophylaxis of graft-versus-host disease. Transplant Proc 15: 1385–1389
Gale RP, Kay HEM, Rimm AA, Bortin MM (1982) Bonemarrow transplantation for acute leukemia in first remission. Lancet II: 1006–1009
Gratwohl A, Bull M, Graw R Jr, Norton L, Knutsen T (1978) Methotrexate and citrovorum factor after histoincompatible allogenic bone marrow transplants in dogs. Acta Hematol 60: 233–242
Hows JM, Kaffaf S, Palmer S, Harris R, Fairhead S, Gordon-Smith EC (1982) Regeneration of peripheral blood cells following allogenic bone marrow transplantation for severe aplastic anemia. Br J Haematol 52: 551–556
Jolivet J, Cowan K, Curt G, Clendeninn N, Chabner B (1983) The pharmacology and clinical use of methotrexate. N Engl J Med 309: 1094–1104
Lazarus HM, Coccia PF, Herzig RH, Graham-Pole J, Gross S, Strandjord S, Gordon E, Cheung NKV, Warkentin PI, Spitzer TR, Warm SE (1984) Incidence of acute graft-versus host disease with and without methotrexate prophylaxis in allogenic bone marrow transplant patients. Blood 64: 215–220
Martin PJ, Hansen JA, Buckner CD (1985) Effects of in vivo depletion of T cells in HLA-identical allogenic marrow grafts. Blood 66: 664–672
Powles RL, Clink HM, Spence D, Morgenstern G, Watson JG, Selby PJ, Woods M, Barrett A, Jameson B, Sloane J, Lawler SD, Kay Hem, Lawson D, McElwain TJ, Alexander P (1980) Cyclosporin A to prevent graft versus host disease in man after allogenic bone-marrow transplantation. Lancet I: 327–329
Prentice HG, Blacklock HA, Janossy G, Bradstock KJ, Skeggs D, Goldstein G, Hoffbrand AV (1982) Use of anti-T-cell monoclonal antibody OKT 3 to prevent acute graftversus-host disease in allogenic bone marrow transplantation for acute leukemia. Lancet I: 700–703
Ramsay NKC, Kersey JH, Robinson LL, McGlave PB, Woods WG, Krivit W, Kim TH, Goldman AI, Nesbit ME Jr (1982) A randomized study of the prevention of acute graft-versus-host disease. N Engl J Med 306: 392–397
Ringden O, Zwaan F, Hermans J, Gratwohl A (1987) European experience of bone marrow transplantation for leukemia. Transplant Proc 19: 2600–2604
Storb R (1984) Pathophysiology and prevention of graft-versus-host disease in: Mc Cullough J, Saudler SG (eds): Advances in Immunobiology: Blood Cell Antigens and Bone Marrow Transplantation. Allan R. Liss, New York, pp 337–366
Storb R, Graham T, Shiruba R, Thomas E (1970) Treatment of canine graft-versus-host disease with methotrexate and cyclophosphamide following bone marrow transplantation from histoincompatible donors. Transplantation 10: 165–169
Storb R, Rudolph R, Kolb H, Graham T, Mickelson E, Erickson V, Lerner K, Kolb H, Thomas E (1973) Marrow grafts between DLA-matched canine littermates. Transplantation 15: 92–100
Storb R, Thomas E, Buckner C, Clift R, Johnson F, Fefer A, Glucrsberg H, Giblett E, Lerner K, Neiman P (1974) Allogenic marrow grafting for treatment of aplastic anemia. Blood 43: 157–180
Storb R, Deeg HJ, Thomas ED, Appelbaum FR, Buckner CD, Cheever MA, Clift RA, Doney KC, Flournoy N, Kennedy MS, Loughran TP, Mc Guffin RW, Sale GR, Sanders JE, Singer JW, Stewart PS, Sullivan KM, Witherspoon RP (1985) Marrow transplantation for chronic myelocytic leukemia: a controlled trial of cyclosporin versus methotrexate for prophylaxis of graft-versus-host disease. Blood 66: 698–702
Storb R, Deeg HJ, Whitehead J, Appelbaum F, Beatty P, Bensinger W, Buckner CD, Clift R, Doney K, Farewell V, Hansen J, Hill R, Lum L, Martin P, McGuffin R, Sanders J, Stewart P, Sullivan K, Witherspoon R, Yee G, Thomas ED (1986) Methotrexate and cyclosporin compared with cyclosporin alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia. N Engl J Med 314: 729–735
Thomas ED, Storb R, Clift RA, Fefer A, Johnson FL, Neiman PE, Lerner KG, Glucksberg H, Buckner CD (1975) Bone marrow transplantation. N Engl J Med 292: 832–843
Tutschka PJ, Farmer E (1981) Therapy of acute graft-versus-host disease (GVHD — Baltimore experience. Exp Hematol [Suppl 9] 9: 126
Tutschka PJ, Beschorner WE, Hess AD, Santos GW (1983) Cyclosporin A to prevent graft versus host disease: a pilot study in 22 patients receiving allogenic marrow transplants. Blood 61: 318–325
Zwaan FE, Hermans J (1982) For the EBMT Leukemia Working Party Bone Marrow Transplantation for leukemia — European results in 264 cases. Exp Hematol [Suppl 10] 10: 64
Zwaan FE, Hermans J (1983) Report of the EBMT Leukemia Working party. Exp Hematol [Suppl 13] 11: 3
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Torres, A., Martinez, F., Gomez, P. et al. Cyclosporin A versus methotrexate, followed by rescue with folinic acid as prophylaxis of acute graft-versus-host disease after bone marrow transplantation. Blut 58, 63–68 (1989). https://doi.org/10.1007/BF00320650
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00320650