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Graft-Versus-Host Disease

MTX or mycophenolate mofetil with CsA as GVHD prophylaxis after reduced-intensity conditioning PBSCT from HLA-identical siblings

Abstract

Mycophenolate mofetil (MMF) in combination with CsA seems to lead to earlier post transplant hematological recovery and less mucositis than MTX, with a similar incidence of GVHD. In this study we analyzed the post transplant outcomes of two cohorts of patients who underwent an HLA-identical sibling reduced intensity conditioning transplantation (allo-RIC) with GVHD prophylaxis consisting of CsA in combination with either MMF or a short course of MTX. We included 145 consecutive allo-RIC transplants performed between April 2000 and August 2007. The median follow-up for survivors was 41 months (4–105 months). The study group included 91 males. Median age was 55 years (range 18–71 years). Diagnoses included myeloid (n=65) and lymphoid (n=80) malignancies. GVHD prophylaxis consisted of CsA/MMF in 52 and CsA/MTX in 93 patients. The conditioning regimen was based on fludarabine in combination with BU (n=59) or melphalan (n=86). The occurrence of grade 2–4 mucositis was higher in the CsA/MTX group than in the CsA/MMF group (57 vs 23%, P=0.001). The cumulative incidence of acute and chronic GVHD was similar, 48 vs 50% and 71 vs 68%, respectively (P>0.7). The 2-year relapse and OS were similar in the CsA/MTX and CsA/MMF groups (29 vs 21%, P=0.3 and 52 vs 51%, P=0.7, respectively). Our results support further prospective studies comparing the use of the CsA/MMF combination with CsA/MTX as GVHD prophylaxis in HLA-identical sibling donor allo-RIC recipients.

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References

  1. Valcarcel D, Martino R, Sureda A, Canals C, Altés A, Briones J et al. Conventional versus reduced-intensity conditioning regimen for allogeneic stem cell transplantation in patients with hematological malignancies. Eur J Haematol 2005; 74: 144–151.

    Article  CAS  PubMed  Google Scholar 

  2. Mielcarek M, Martin PJ, Leisenring W, Flowers M, Maloney D, Sandmaier B et al. Graft-versus-host disease after nonmyeloablative versus conventional hematopoietic stem cell transplantation. Blood 2003; 102: 756–762.

    Article  CAS  PubMed  Google Scholar 

  3. Storb R, Deeg HJ, Whitehead J, Appelbaum F, Beatty P, Bensinger W 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.

    Article  CAS  PubMed  Google Scholar 

  4. Storb R, Deeg HJ, Pepe M, Appelbaum F, Anasetti C, Beatty P 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.

    CAS  PubMed  Google Scholar 

  5. Neumann F, Graef T, Tapprich C, Vaupel M, Steidl U, Germing U et al. Cyclosporine A and mycophenolate mofetil vs cyclosporine A and methotrexate for graft-versus-host disease prophylaxis after stem cell transplantation from HLA-identical siblings. Bone Marrow Transplant 2005; 35: 1089–1093.

    Article  CAS  PubMed  Google Scholar 

  6. Cutler C, Li S, Kim HT, Laglenne P, Szeto K, Hoffmeister L et al. Mucositis after allogeneic hematopoietic stem cell transplantation: a cohort study of methotrexate-and non-methotrexate-containing graft-versus-host disease prophylaxis regimens. Biol Blood Marrow Transplant 2005; 11: 383–388.

    Article  CAS  PubMed  Google Scholar 

  7. Ho VT, Weller E, Lee SJ, Edwin P, Alyea E, Antin JH, Soiffer R et al. Prognostic factors for early severe pulmonary complications after hematopoietic stem cell transplantation. Biol Blood and Marrow Transplant 2001; 7: 223–229.

    Article  CAS  Google Scholar 

  8. Piñana JL, Valcárcel D, Martino R, Barba P, Moreno E, Sureda A et al. Study of kidney function impairment after reduced intensity conditioning allogeneic hematopoietic stem cell transplantation A single centre experience. Biol Blood Marrow Transplant 2009; 15: 21–29.

    Article  PubMed  Google Scholar 

  9. McSweeney PA, Niederwieser D, Shizuru JA, Sandmaier BM, Molina AJ, Maloney DG 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.

    Article  CAS  PubMed  Google Scholar 

  10. Bolwell B, Sobecks R, Pohlman B, Andresen S, Rybicki L, Kuczkowski E et al. A prospective randomized trial comparing cyclosporine and short course methotrexate with cyclosporine and mycophenolate mofetil for GVHD prophylaxis in myeloablative allogeneic bone marrow transplantation. Bone Marrow Transplant 2004; 34: 621–625.

    Article  CAS  PubMed  Google Scholar 

  11. Bornhauser M, Schuller U, Pörksen G, Geissler G, Thiede C, Schwerdtfeger R et al. Mycophenolate mofetil and cyclosporine as graft-versus-host disease prophylaxis after allogeneic blood stem cell transplantation. Transplantation 1999; 67: 499.

    Article  CAS  PubMed  Google Scholar 

  12. Martino R, Caballero MD, Canals C, Simón JA, Solano C, Urbano-Ispízua A et al. Allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning: results of a prospective multicentre study. Br J Haematol 2001; 115: 653–659.

    Article  CAS  PubMed  Google Scholar 

  13. Pérez-Simón JA, Díez-Campelo M, Martino R, Brunet S, Urbano A, Caballero MD et al. Influence of the intensity of the conditioning regimen on the characteristics of acute and chronic graft-versus-host disease after allogeneic transplantation. Br J Haematol 2005; 130: 394–403.

    Article  PubMed  Google Scholar 

  14. Przepiorka D, Weisdorf D, Martin P . Meeting report consensus conference on acute GVHD grading. Bone Marrow Transplant 1995; 15: 825–828.

    CAS  PubMed  Google Scholar 

  15. Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ et al. National institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: i. Diagnosis and staging working group report. Biol Blood Marrow Transplant 2005; 11: 945–956.

    Article  PubMed  Google Scholar 

  16. Valcarcel D, Martino R, Caballero D, Mateos MV, Pérez-Simón JA, Canals C et al. Chimerism analysis following allogeneic peripheral blood stem cell transplantation with reducedintensity conditioning. Bone Marrow Transplant 2003; 31: 387–392.

    Article  CAS  PubMed  Google Scholar 

  17. Klein JP, Rizzo JD, Zhang MJ, Keiding N . Statistical methods for the analysis and presentation of the results of bone marrow transplants. Part I: Unadjusted analysis. Bone Marrow Transplant 2001; 28: 909–915.

    Article  CAS  PubMed  Google Scholar 

  18. Klein JP, Rizzo JD, Zhang MJ, Keiding N . Statistical methods for the analysis and presentation of the results of bone marrow transplants. Part 2: Regression modeling. Bone Marrow Transplant 2001; 28: 1001–1011.

    Article  CAS  PubMed  Google Scholar 

  19. Kaplan EL, Meier P . Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958, 457–481.

    Article  Google Scholar 

  20. Baron F, Maris MB, Sandmaier BM, Storer BE, Sorror M, Diaconescu R et al. Graft-versus-tumor effects after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning. J Clin Oncol 2005; 23: 1993–2003.

    Article  PubMed  Google Scholar 

  21. Kiehl MG, Schäfer-Eckart K, Kröger M, Bornhäuser M, Basara N, Blau IW et al. Mycophenolate mofetil for the prophylaxis of acute graft-versus-host disease in stem cell transplant recipients. Transplant Proc 2002; 34: 2922–2924.

    Article  CAS  PubMed  Google Scholar 

  22. Van Leeuwen L, Guiffre AK, Sewell WA, Vos BJ, Rainer S, Atkinson K et al. Administration of mycophenolate mofetil in a murine model of acute graft-versus-host disease after bone marrow transplantation. Transplantation 1997; 64: 1001–1097.

    Article  Google Scholar 

  23. Simmons WD, Rayhill SC, Sollinger HW . Preliminary risk-benefit assessment of mycophenolate mofetil in transplant rejection. Drug Safety 1997; 17: 75–92.

    Article  CAS  PubMed  Google Scholar 

  24. Flynn CM, Hirsch B, Defor T, Barker JN, Miller JS, Wagner JE et al. Reduced intensity compared with high dose conditioning for allotransplantation in acute myeloid leukemia and myelodysplastic syndrome: a comparative clinical analysis. Am J Hematol 2007; 82: 867–872.

    Article  PubMed  Google Scholar 

  25. Bensinger WI, Martin PJ, Storer B, Clift R, Forman SJ, Negrin R et al. Transplantation of bone marrow as compared with peripheral-blood cells from HLA-identical relatives in patients with hematologic cancers. N Engl J Med 2001; 344: 175–181.

    Article  CAS  PubMed  Google Scholar 

  26. Champlin RE, Schmitz N, Horowitz MM, Chapuis B, Chopra R, Cornelissen JJ et al. Blood stem cells compared with bone marrow as a source of hematopoietic cells for allogeneic transplantation. Blood 2000; 95: 3702–3709.

    CAS  PubMed  Google Scholar 

  27. Van Gelder T, Klupp J, Barten MJ, Christians U, Morris RE . Comparison of the effects of tacrolimus and cyclosporine on the pharmacokinetics of mycophenolic acid. Ther Drug Monit 2001; 23: 119–128.

    Article  CAS  PubMed  Google Scholar 

  28. Lange S, Mueller SC, Altmann S, Dahlhaus M, Drewelow B, Freund M et al. Pharmacokinetics of oral mycophenolate mofetil in combination with CsA in dogs after nonmyeloablative allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2007; 41: 667–674.

    Article  PubMed  Google Scholar 

  29. Pérez-Simón JA, Martino R, Caballero D, Valcarcel D, Rebollo N, de la Cámara R et al. Grupo español de trasplante hematopoyético GETH. Reduced-intensity conditioning allogeneic transplantation from unrelated donors: evaluation of mycophenolate mofetil plus cyclosporin a as graft-versus-host disease prophylaxis. Biol Blood Marrow Transplant 2008; 14: 664–671.

    Article  PubMed  Google Scholar 

  30. Giaccone L, McCune JS, Maris MB, Gooley TA, Sandmaier BM, Slattery JT et al. Pharmacodynamics of mycophenolate mofetil after nonmyeloablative conditioning and unrelated donor hematopoietic cell transplantation. Blood 2005; 106: 4381.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Storb R, Yu C, Wagner JL, Deeg HJ, Nash RA, Kiem HP 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.

    CAS  PubMed  Google Scholar 

  32. Gómez-Núñez M, Martino R, Caballero MD, Pérez-Simón JA, Canals C, Mateos MV et al. Elderly age and prior autologous transplantation have a deleterious effect on survival following allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning: results from the Spanish multicenter prospective trial. Bone Marrow Transplant 2004; 33: 477–482.

    Article  PubMed  Google Scholar 

  33. Michallet M, Le QH, Mohty M, Prébet T, Nicolini F, Boiron JM et al. Predictive factors for outcomes after reduced intensity conditioning hematopoietic stem cell transplantation for hematological malignancies: a 10-year retrospective analysis from the Société FranÇaise de Greffe de Moelle et de Thérapie Cellulaire. Exp Hematol 2008; 36: 535–544.

    Article  PubMed  Google Scholar 

  34. Van Besien KW, Mehra RC, Giralt SA, Kantarjian HM, Pugh WC, Khouri IF et al. Allogeneic bone marrow transplantation for poor-prognosis lymphoma: response, toxicity and survival depend on disease histology. Am J Med 1996; 100: 299–307.

    Article  CAS  PubMed  Google Scholar 

  35. Bearman SI, Appelbaum FR, Back A, Petersen FB, Buckner CD, Sullivan KM et al. Regimen-related toxicity and early posttransplant survival in patients undergoing marrow transplantation for lymphoma. J Clin Oncol 1989; 7: 1288–1294.

    Article  CAS  PubMed  Google Scholar 

  36. Mohty M, Fegueux N, Exbrayat C, Lu ZY, Legouffe E, Quittet P et al. Reduced intensity conditioning: enhanced graft-versus-tumor effect following dose-reduced conditioning and allogeneic transplantation for refractory lymphoid malignancies after high-dose therapy. Bone Marrow Transplant 2001; 28: 335–339.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

JL Piñana was supported by grants from the Instituto de Salud Carlos III (CM06/00139, Ministerio de Sanidad, Spain).

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Piñana, J., Valcárcel, D., Fernández-Avilés, F. et al. MTX or mycophenolate mofetil with CsA as GVHD prophylaxis after reduced-intensity conditioning PBSCT from HLA-identical siblings. Bone Marrow Transplant 45, 1449–1456 (2010). https://doi.org/10.1038/bmt.2009.362

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