Biology of Blood and Marrow Transplantation
Volume 14, Issue 6 , Pages 664-671 , June 2008

Reduced-Intensity Conditioning Allogeneic Transplantation from Unrelated Donors: Evaluation of Mycophenolate Mofetil Plus Cyclosporin A as Graft-versus-Host Disease Prophylaxis

  • Jose A. Pérez-Simón

      Affiliations

    • Servicio de Hematología, Hospital Clínico Universitario de Salamanca
    • Corresponding Author InformationCorrespondence and reprint requests: José A Pérez-Simón, MD, PhD, Servicio de Hematología, Hospital Clínico Universitario de Salamanca, Paseo de San Vicente 37007, Salamanca, Spain.
  • ,
  • Rodrigo Martino

      Affiliations

    • Hospital Santa Creu i Sant Pau, Barcelona, Spain
  • ,
  • Dolores Caballero

      Affiliations

    • Servicio de Hematología, Hospital Clínico Universitario de Salamanca
  • ,
  • David Valcarcel

      Affiliations

    • Hospital Santa Creu i Sant Pau, Barcelona, Spain
  • ,
  • Noemi Rebollo

      Affiliations

    • Servicio de Farmacia, Hospital Clínico Universitario de Salamanca, Spain
  • ,
  • Rafael de la Cámara

      Affiliations

    • Hospital de la Princesa, Madrid, Spain
  • ,
  • Javier Pérez de Oteiza

      Affiliations

    • Hospital Ramón y Cajal, Madrid, Spain
  • ,
  • Inmaculada Heras

      Affiliations

    • Hospital Morales Meseguer, Murcia, Spain
  • ,
  • Maria V. Calvo

      Affiliations

    • Servicio de Farmacia, Hospital Clínico Universitario de Salamanca, Spain
  • ,
  • Jordi Sierra

      Affiliations

    • Hospital Santa Creu i Sant Pau, Barcelona, Spain
  • ,
  • Jesús F. San Miguel

      Affiliations

    • Servicio de Hematología, Hospital Clínico Universitario de Salamanca
  • ,
  • Grupo Español de Trasplante Hematopoyético (GETH)

Received 21 February 2008 ,Accepted 19 March 2008.

References 

  1. Thomas E, Storb R, Clift R, et al. Bone marrow transplantation. N Eng J Med. 1975;292:832–843
  2. Lima M, Champlin R. Unrelated donor hematopoietic transplantation. Rev Clin Exp Hematol. 2001;5:100–134
  3. Hurley C, Lowe LA, Logan B, et al. National Marrow Donor Program HLA matching guidelines for unrelated marrow transplants. Biol Blood Marrow Transplant. 2003;9:610–615
  4. Dini G, Cancedda R, Locatelli F, et al. Unrelated donor marrow transplantation: an update of the experience of the Italian Bone Marrow Transplant Group (GITMO). Hematologica. 2001;86:15–20
  5. Castro-Malaspina H, Harris R, Gajewski J, et al. Unrelated donor marrow transplantation for myelodisplastic síndromes: outcome análisis in 510 transplants facilitated by the National Marrow Donor Program. Blood. 2002;99:1943–1951
  6. Flomemberg N, Baxter-Lowe LA, Confer DL, et al. Impact of class I and LL high resolution matching on outcomes of unrelated donor bone marrow transplantation: HLA-C mismatching is associated with a strong adverse effect on transplantation outcome. Blood. 2004;104:1923–1930
  7. Winston D, Maziarz R, Chandrasekar P, et al. Intravenous and oral itraconazole versus intravenous and oral fluconazole for long term antifungal prophylaxis in allogeneic hematopoietic stem cell transplant recipients. Ann Intern Med. 2003;138:705–713
  8. Slavin M, Osborne B, Adams R, et al. Efficacy and safety of fluconazol prophylaxis for fungal infections after marrow transplantation: a prospective, randomized, double blind study. J Infect Dis. 1995;171:1545–1554
  9. Xun CQ, Thompson JS, Jeyapalan S, et al. Effect of total body irradiation, busulphan-cyclophsophamide or cyclophosphamide conditioning on inflammatory cytokine release and development of acute and chronic graft versus host disease in H-2 incompatible transplanted SCID mice. Blood. 1994;83:2360–2367
  10. Ratanatharathorn V, Nash R, Przepiorka D, et al. Phase III study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for graft versus host disease prophylaxis after HLA identical sibling bone marrow transplantation. Blood. 1998;92:2303–2314
  11. Weisdorf D, Anasetti C, Antin J, et al. Allogeneic bone marrow transplantation for chronic myelogenous leukemia: comparative analysis of unrelated versus matched sibling donor transplantation. Blood. 2002;15:1971–1977
  12. Yakoub-Agha I, Mensil F, Kuentz M, et al. Allogeneic marrow stem cell transplantation from human leukocyte antigen identical sibling versus human leukocyte antigen matched unrelated donor (10/10) in patients with standard risk hematopoietic malignancy: a prospective study from the French Society of Bone Marrow Transplantation and Cell Therapy. J Clin Oncol. 2006;24:5695–5702
  13. Carreras E, Tomás JF, Sanz G, et al. Unrelated donor bone marrow transplantation as treatment for chronic myeloid leukemia: the Spanish experience. Hematologica. 2000;85:530–538
  14. McGlave P, Shu X, Wen W, et al. Unrelated donor marrow transplantation for chronic myelogenous leukemia: 9 years' experience of the National Marrow Donor Program. Blood. 2000;95:2219–2225
  15. Cornelissen J, Carston M, Kollman C, et al. Unrelated marrow transplantation for adult patients with poor risk acute lymphoblastic leukemia: strong graft versus leukemmia effect and risk factors determining ourcome. Blood. 2001;97:1572–1577
  16. Radich JP, Gooley T, Sanders JE, et al. Second allogeneic transplantation after failure of first autologous transplantation. Biol Blood Marrow Transplant. 2000;6:272–279
  17. Tsai T, Goodman S, Saez R, et al. Allogeneic bone marrow transplantation in patients who relapse after an autologous transplantation. Bone Marrow Transplant. 1997;20:859–863
  18. Pérez-Simón JA, Kottaridis P, Martino R, et al. Non-myeloablative transplants with or without CAMPATH-1H: comparison between two prospective studies in patients with lymphoproliferative disorders. Blood. 2002;100:3121–3127
  19. Kröger N, Shaw B, Iacobelli S, et al. Comparison between antithymocyte globulin and alemtuzumab and the possible impact of KIR-ligand mismatch after dose-reduced conditioning and unrelated stem cell transplantation in patients with multiple myeloma. Br J Hematol. 2005;129:631–643
  20. Slavin S, Nagler A, Naparstek E, et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with letal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood. 1998;91:756–763
  21. Giralt S, Estey E, Albitar M, et al. Engraftment of allogeneic hematopoietic progenitor cells wirrh purine analog-containing chemotherapy: harnessing graft versus leukemia without myeloablative therapy. Blood. 1997;89:4531–4536
  22. Wong R, Giralt S, Martín T, et al. Reduced intensity conditioning for unrelated donor hematopoietic transplantation as treatment for myeloid malignancies in patients older than 55 years. Blood. 2003;102:3052–3059
  23. Kröger N, Sayer HG, Schwerdtfeger R, et al. Unrelated stem cell transplantation in multiple myeloma after a reduced intensity conditioning with pretransplantation antithymmocyte globulin is highly effective with low transplantation related mortality. Blood. 2002;100:3919–3924
  24. Lim Z, Ho A, Ingram W, et al. Outcomes of alemtuzumab based reduced intensity conditioing stem cell transplantation using unrelated donors for myelodisplastic syndromes. Br J Hematol. 2006;135:201–209
  25. Delgado J, Thomson K, Russell N, et al. Results of alemtuzumab based reduced intensity allogeneic transplantation for chronic lymphocytic leukemia: a British Society of Blood and Marrow Transplantation study. Blood. 2006;107:1724–1730
  26. Morris E, Thomson K, Craddock C, et al. Outcomes after alemtuzumab containing reduced intensity allogeneic transplantation regimen for relapsed and refractory non-Hodgkin lymphoma. Blood. 2004;104:3865–3871
  27. Bolwell B, Sobecks R, Pohlman B, 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
  28. Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus conference on acute GVHD grading. Bone Marrow Transplant. 1995;15:825–828
  29. Sullivan KM, Shulman HM, Storb R, et al. Chronic graft-versus-host disease in 52 patients: adverse natural course and successful treatment with combination immunosuppression. Blood. 1981;57:267–276
  30. Rodriguez R, Parker P, Nademanee A, et al. Cyclosporine and mycophenolate mofetil prophylaxis with fludarabine and melphalan conditioning for unrelated donor transplantation: a prospective study of 22 patients with hematologic malignancies. Bone Marrow Transplant. 2004;33:1123–1129
  31. Maris M, Niederwieser D, Sandmaier B, et al. HLA matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies. Blood. 2003;102:2021–2030
  32. Pérez-Simón JA, Díez-Campelo M, Martino R, 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 Hematol. 2005;130:394–403
  33. Sorror M, Maris M, Storer B, et al. Comparing morbidity and mortality of HLA-matched unrelated donor hematopoietic stem cell tramsplantation after non-myeloablative and myeloablative conditioning: influence of pretransplantation comorbidities. Blood. 2004;104:961–968
  34. Kahl C, Storer BE, Sandmaier BM, Mielkarek M, et al. Relapse risk in patients with malignant diseases given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. Blood. 2007;110:2744–2748
  35. de Lima M, Anagnostopoulos A, Munsell M, et al. Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome: dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation. Blood. 2004;104:865–872
  36. Claxon D, Ehmann C, Rybka W, et al. Control of advanced and refractory acute myelogenous leukemia with sirolimus based non-myeloablative allogeneic stem cell transplantation. Br J Hematol. 2005;130:256–264
  37. Caballero D, García-Marco JA, Martino R, et al. Allogeneic transplant with reduced intensity conditioning regimens may overcome the poor prognosis of B-cell chronic lymphocytic leukemia with unmutated immunoglobulin variable heavy-chain gene and chromosomal abnormalities (11q- and 17p-). Clin Cancer Res. 2005;11:7757–7763
  38. Valcárcel D, Martino R, Caballero D, et al. Sustained remissions of high-risk acute myeloid leukemia and myelodysplastic syndrome after reduced-intensity conditioning allogeneic hematopoietic transplantation: chronic graft-versus-host disease is the strongest factor improving survival. J Clin Oncol. 2008;26:577–584
  39. Yakoub-Agha I, Mesnil F, Kuentz M, et al. Allogeneic marrow stem-cell transplantation from human leukocyte antigen-identical siblings versus human leukocyte antigen-allelic-matched unrelated donors (10/10) in patients with standard-risk hematologic malignancy: a prospective study from the French Society of Bone Marrow Transplantation and Cell Therapy. J Clin Oncol. 2006;24:5695–5702
  40. Weber LT, Shipkova M, Armstrong VW, et al. The pharmacokinetic-pharmacodynamic relationship for total and free mycophenolic acid in pediatric renal transplant recipients: a report of the German study group on mycophenolate mofetil therapy. J Am Soc Nephrol. 2002;13:759–768
  41. Giaccone L, McCune JS, Maris MB, et al. Pharmacodynamics of mycophenolate mofetil after nonmyeloablative conditioning and unrelated donor hematopoietic cell transplantation. Blood. 2005;106:4381–4388
  42. Jacobson J, Rogosheske J, Barker JN, et al. Relationship of mycophenolic acid exposure to clinical outcome after hematopoietic cell transplantation. Clin Pharmacol Ther. 2005;78:486–500
  43. Cox VC, Ensom HH. Mycophenolate mofetil for solid organ transplantation: does the evidence support the need for clinical pharmacokinetic monitoring?. Ther Drug Monit. 2003;25:137–157
  44. Van Hest RM, Mathot RA, Vulto AG, et al. Within-patient variability of mycophenolic acid exposure. Therapeutic drug monitoring from a clinical point of view. Ther Drug Monit. 2006;28:31–34

PII: S1083-8791(08)00116-X

doi: 10.1016/j.bbmt.2008.03.007

Biology of Blood and Marrow Transplantation
Volume 14, Issue 6 , Pages 664-671 , June 2008