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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Przepiorka D, Weisdorf D, Martin P . Meeting report consensus conference on acute GVHD grading. Bone Marrow Transplant 1995; 15: 825–828.
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.
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.
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.
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.
Kaplan EL, Meier P . Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958, 457–481.
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.
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.
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.
Simmons WD, Rayhill SC, Sollinger HW . Preliminary risk-benefit assessment of mycophenolate mofetil in transplant rejection. Drug Safety 1997; 17: 75–92.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Acknowledgements
JL Piñana was supported by grants from the Instituto de Salud Carlos III (CM06/00139, Ministerio de Sanidad, Spain).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Rights and permissions
About this article
Cite this article
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
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/bmt.2009.362
Keywords
This article is cited by
-
Patterns of infection and infectious-related mortality in patients receiving post-transplant high dose cyclophosphamide as graft-versus-host-disease prophylaxis: impact of HLA donor matching
Bone Marrow Transplantation (2021)
-
Comparison of mycophenolate mofetil and calcineurin inhibitor versus calcineurin inhibitor-based graft-versus-host-disease prophylaxis for matched unrelated donor transplant in acute myeloid leukemia. A study from the ALWP of the EBMT
Bone Marrow Transplantation (2021)
-
A prospective single-center study on CNI-free GVHD prophylaxis with everolimus plus mycophenolate mofetil in allogeneic HCT
Annals of Hematology (2021)
-
Incorporating posttransplant cyclophosphamide-based prophylaxis as standard-of-care outside the haploidentical setting: challenges and review of the literature
Bone Marrow Transplantation (2020)
-
Pharmacokinetics of intravenous mycophenolate mofetil in allogeneic hematopoietic stem cell-transplanted Japanese patients
Cancer Chemotherapy and Pharmacology (2018)