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Graft-Versus-Host Disease

Ultra-short course sirolimus contributes to effective GVHD prophylaxis after reduced-intensity allogeneic hematopoietic cell transplantation

Bone Marrow Transplantation volume 47, pages 1552–1557 (2012)Cite this article

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Abstract

Reduced-intensity conditioning (RIC) allo-SCT is a potentially curative treatment approach for patients with relapsed Hodgkin’s or non-Hodgkin’s lymphoma. In the present study, 37 patients underwent RIC allo-SCT after induction treatment with EPOCH-F(R) using a novel form of dual-agent immunosuppression for GVHD prophylaxis with CsA and sirolimus. With a median follow-up of 28 months among survivors, the probability for OS at 3 and 5 years was 56%. Treatment-related mortality was 16% at day +100 and 30% after 1 year of transplant. Acute GVHD grades II–IV developed in 38% of patients, suggesting that the regimen consisting of CsA and an ultra-short course of sirolimus is effective in the prevention of acute GVHD.

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References

  1. Pinana JL, Martino R, Gayoso J, Sureda A, de la Serna J, Díez-Martín JL et al. GELTAMO Group. Reduced intensity conditioning HLA identical sibling donor allogeneic stem cell transplantation for patients with follicular lymphoma: long-term follow-up from two prospective multicenter trials. Haematologica 2010; 95: 1176–1182.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Cook G, Smith GM, Kirkland K, Lee J, Pearce R, Thomson K et al. Clinical Trials Committee (CTC) of the British Society for Blood and Marrow Transplantation (BSBMT). Outcome following Reduced-Intensity Allogeneic Stem Cell Transplantation (RIC AlloSCT) for relapsed and refractory mantle cell lymphoma (MCL): a study of the British Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant 2010; 16: 1419–1427.

    Article  PubMed  Google Scholar 

  3. Weigert O, Unterhalt M, Hiddemann W, Dreyling M . Mantle cell lymphoma: state-of-the-art management and future perspective. Leuk Lymphoma 2009; 50: 1937–1950.

    Article  CAS  PubMed  Google Scholar 

  4. van Kampen RJ, Canals C, Schouten HC, Nagler A, Thomson KJ, Vernant JP et al. Allogeneic Stem-Cell Transplantation As Salvage Therapy for Patients With Diffuse Large B-Cell Non-Hodgkin's Lymphoma Relapsing After an Autologous Stem-Cell Transplantation: An Analysis of the European Group for Blood and Marrow Transplantation Registry. J Clin Oncol 2011; 29: 1342–1348.

    Article  PubMed  Google Scholar 

  5. Claviez A, Canals C, Dierickx D, Stein J, Badell I, Pession A et al. Allogeneic hematopoietic stem cell transplantation in children and adolescents with recurrent and refractory Hodgkin lymphoma: an analysis of the European Group for Blood and Marrow Transplantation. Blood 2009; 114: 2060–2067.

    Article  CAS  PubMed  Google Scholar 

  6. Robinson SP, Goldstone AH, Mackinnon S, Carella A, Russell N, de Elvira CR et al. Chemoresistant or aggressive lymphoma predicts for a poor outcome following reduced-intensity allogeneic progenitor cell transplantation: an analysis from the Lymphoma Working Party of the European Group for Blood and Bone Marrow Transplantation. Blood 2002; 100: 4310–4316.

    Article  CAS  PubMed  Google Scholar 

  7. Vigouroux S, Michallet M, Porcher R, Attal M, Ades L, Bernard M et al. Long-term outcomes after reduced-intensity conditioning allogeneic stem cell transplantation for low-grade lymphoma: a survey by the French Society of Bone Marrow Graft Transplantation and Cellular Therapy (SFGM-TC). Haematologica 2007; 92: 627–634.

    Article  PubMed  Google Scholar 

  8. Bishop MR, Hou JW, Wilson WH, Steinberg SM, Odom J, Castro K et al. Establishment of early donor engraftment after reduced-intensity allogeneic hematopoietic stem cell transplantation to potentiate the graft-versus-lymphoma effect against refractory lymphomas. Biol Blood Marrow Transplant 2003; 9: 162–169.

    Article  PubMed  Google Scholar 

  9. Cutler C, Li S, Ho VT, Koreth J, Alyea E, Soiffer RJ et al. Extended follow-up of methotrexate-free immunosuppression using sirolimus and tacrolimus in related and unrelated donor peripheral blood stem cell transplantation. Blood 2007; 109: 3108–3114.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Kuypers DR, Herelixka A, Vanrenterghem Y . Clinical use of rapamycin in renal allograft recipients identifies its relevant toxicity profile and raises unsolved questions: a single-center experience. Transplant Proc 2003; 35(3 Suppl): 138S–142SS.

    Article  CAS  PubMed  Google Scholar 

  11. Cutler C, Henry NL, Magee C, Li S, Kim HT, Alyea E et al. Sirolimus and thrombotic microangiopathy after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2005; 11: 551–557.

    Article  CAS  PubMed  Google Scholar 

  12. Weiner SM, Sellin L, Vonend O, Schenker P, Buchner NJ, Flecken M et al. Pneumonitis associated with sirolimus: clinical characteristics, risk factors and outcome--a single-centre experience and review of the literature. Nephrol Dial Transplant 2007; 22: 3631–3637.

    Article  CAS  PubMed  Google Scholar 

  13. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant 1995; 15: 825–828.

    CAS  PubMed  Google Scholar 

  14. 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 

  15. Sorror ML . Comorbidities and hematopoietic cell transplantation outcomes. Hematol Am Soc Hematol Educ Program 2010; 2010: 237–247.

    Article  Google Scholar 

  16. Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood 2005; 106: 2912–2919.

    Article  CAS  PubMed  PubMed Central  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. Dean RM, Fowler DH, Wilson WH, Odom J, Steinberg SM, Chow C et al. Efficacy of reduced-intensity allogeneic stem cell transplantation in chemotherapy-refractory non-hodgkin lymphoma. Biol Blood Marrow Transplant 2005; 11: 593–599.

    Article  PubMed  Google Scholar 

  19. Jamshed S, Fowler DH, Neelapu SS, Dean RM, Steinberg SM, Odom J et al. EPOCH-F: a novel salvage regimen for multiple myeloma before reduced-intensity allogeneic hematopoietic SCT. Bone Marrow Transplant 2011; 46: 676–681.

    Article  CAS  PubMed  Google Scholar 

  20. Keil F, Kalhs P, Chen X, Haas OA, Fritsch G, Chott A et al. Hematopoietic donor chimerism and graft-versus-myeloma effect in relapse of multiple myeloma after allogeneic bone marrow transplantation. Ann Hematol 1999; 78: 376–379.

    Article  CAS  PubMed  Google Scholar 

  21. Chakraverty R, Mackinnon S . Allogeneic transplantation for lymphoma. J Clin Oncol 2011; 29: 1855–1863.

    Article  PubMed  Google Scholar 

  22. Kolb HJ. . Graft-versus-leukemia effects of transplantation and donor lymphocytes. Blood 2008; 112: 4371–4383.

    Article  CAS  PubMed  Google Scholar 

  23. Maris MB, Sandmaier BM, Storer BE, Chauncey T, Stuart MJ, Maziarz RT et al. Allogeneic hematopoietic cell transplantation after fludarabine and 2 Gy total body irradiation for relapsed and refractory mantle cell lymphoma. Blood 2004; 104: 3535–3542.

    Article  CAS  PubMed  Google Scholar 

  24. Hari P, Carreras J, Zhang MJ, Gale RP, Bolwell BJ, Bredeson CN et al. Allogeneic transplants in follicular lymphoma: higher risk of disease progression after reduced-intensity compared to myeloablative conditioning. Biol Blood Marrow Transplant 2008; 14: 236–245.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Rezvani AR, Norasetthada L, Gooley T, Sorror M, Bouvier ME, Sahebi F et al. Non-myeloablative allogeneic haematopoietic cell transplantation for relapsed diffuse large B-cell lymphoma: a multicentre experience. Br J Haematol 2008; 143: 395–403.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Corradini P, Dodero A, Zallio F, Caracciolo D, Casini M, Bregni M et al. Graft-versus-lymphoma effect in relapsed peripheral T-cell non-Hodgkin's lymphomas after reduced-intensity conditioning followed by allogeneic transplantation of hematopoietic cells. J Clin Oncol 2004; 22: 2172–2176.

    Article  PubMed  Google Scholar 

  27. Cutler C, Antin JH . Sirolimus immunosuppression for graft-versus-host disease prophylaxis and therapy: an update. Curr Opin Hematol 2010; 17: 500–504.

    Article  CAS  PubMed  Google Scholar 

  28. De Serres SA, Sayegh MH, Najafian N . Immunosuppressive drugs and Tregs: a critical evaluation!. Clin J Am Soc Nephrol 2009; 4: 1661–1669.

    Article  CAS  PubMed  Google Scholar 

  29. Fowler DH, Odom J, Steinberg SM, Chow CK, Foley J, Kogan Y et al. Phase I clinical trial of costimulated, IL-4 polarized donor CD4+ T cells as augmentation of allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2006; 12: 1150–1160.

    Article  CAS  PubMed  Google Scholar 

  30. Norlin AC, Sairafi D, Mattsson J, Ljungman P, Ringden O, Remberger M . Allogeneic stem cell transplantation: low immunoglobulin levels associated with decreased survival. Bone Marrow Transplant 2008; 41: 267–273.

    Article  CAS  PubMed  Google Scholar 

  31. Kuzmina Z, Greinix HT, Weigl R, Körmöczi U, Rottal A, Frantal S et al. Significant differences in B-cell subpopulations characterize patients with chronic graft-versus-host disease-associated dysgammaglobulinemia. Blood 2011; 117: 2265–2274.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Hematology, Oslo University Hospital, Oslo, Norway

    Y Fløisand, L Brinch, T Gedde-Dahl, G E Tjønnfjord, I Dybedal & D Heldal

  2. Institute of Clinical Medicine, University of Oslo, Oslo, Norway

    G E Tjønnfjord

  3. Department of Oncology, Oslo University Hospital, Oslo, Norway

    H Holte, D Torfoss, E Aurlien, G F Lauritzsen, A Fosså, G Lehne, E Baggerød & A Kolstad

  4. Department of Cellular Therapy, Oslo University Hospital, Oslo, Norway

    G Kvalheim

  5. Institute of Immunology, Oslo University Hospital, Oslo, Norway

    T Egeland

  6. Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

    M R Bishop & D H Fowler

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Correspondence to Y Fløisand.

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Fløisand, Y., Brinch, L., Gedde-Dahl, T. et al. Ultra-short course sirolimus contributes to effective GVHD prophylaxis after reduced-intensity allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 47, 1552–1557 (2012). https://doi.org/10.1038/bmt.2012.63

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