Experimental Hematology
Volume 36, Issue 5 , Pages 535-544 , May 2008

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

  • Mauricette Michallet

      Affiliations

    • Service d'Hématologie, Hôpital Edouard Herriot, Lyon, France
    • Drs. Michallet and Mohty contributed equally to this study.
  • ,
  • Quoc-Hung Le

      Affiliations

    • Service d'Hématologie, Hôpital Edouard Herriot, Lyon, France
  • ,
  • Mohamad Mohty

      Affiliations

    • Hôpital Hôtel-Dieu, CHU de Nantes, Nantes, France
    • Drs. Michallet and Mohty contributed equally to this study.
    • Corresponding Author InformationOffprint requests to: Mohamad. Mohty, M.D., Ph.D., Hématologie Clinique, Université de Nantes-INSERM UMR U601, CHU Hôtel-Dieu, Place Alexis Ricordeau, F-44093 Nantes Cedex 01, France
  • ,
  • Thomas Prébet

      Affiliations

    • Service d'Hématologie, Hôpital Edouard Herriot, Lyon, France
    • Dr. Prébet is currently at the Département d'Hématologie, Institut Paoli-Calmettes, Marseille, France.
  • ,
  • Franck Nicolini

      Affiliations

    • Service d'Hématologie, Hôpital Edouard Herriot, Lyon, France
  • ,
  • Jean Michel Boiron

      Affiliations

    • Service d'Hématologie Hôpital Pessac, Bordeaux, France
    • Dr. Boiron is currently at EFS de Bordeaux, Bordeaux, France.
  • ,
  • Hélène Esperou

      Affiliations

    • Unité de Greffe de Moelle Osseuse, Hôpital St Louis, Paris, France
  • ,
  • Michel Attal

      Affiliations

    • Service d'Hématologie, Hôpital Purpan, Toulouse, France
  • ,
  • Noel Milpied

      Affiliations

    • Hôpital Hôtel-Dieu, CHU de Nantes, Nantes, France
    • Dr. Milpied is currently at Service d'Hématologie Hôpital Pessac, Bordeaux, France.
  • ,
  • Bruno Lioure

      Affiliations

    • Service d'Hématologie, Hôpital Hautepierre, Strasbourg, France
  • ,
  • Pierre Bordigoni

      Affiliations

    • Service d'Hématologie, Hôpital Nancy, Nancy, France
  • ,
  • Ibrahim Yakoub-Agha

      Affiliations

    • Service d'Hématologie, Hôpital Huriez, Lille, France
  • ,
  • Jean-Henri Bourhis

      Affiliations

    • Service d'Hématologie, Institut Gustave Roussy, Villejuif, France
  • ,
  • Bernard Rio

      Affiliations

    • Service d'Hématologie, Hôpital Hotel Dieu, Paris, France
  • ,
  • Eric Deconinck

      Affiliations

    • Service d'Hématologie, Hôpital Besançon, Besançon, France
  • ,
  • Marc Renaud

      Affiliations

    • Service d'Hématologie, Hôpital Poitiers, Poitiers, France
  • ,
  • Zina Chir

      Affiliations

    • Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC), Agence de Biomédecine, Paris, France
  • ,
  • Didier Blaise

      Affiliations

    • Institut Paoli-Calmettes, Marseille, France

Received 8 September 2007 ,Revised 3 January 2008 ,Accepted 11 January 2008.

References 

  1. Sullivan KM, Weiden PL, Storb R, et al. Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia. Blood. 1989;73:1720–1728
  2. Ringden O, Horowitz MM, Gale RP, et al. Outcome after allogeneic bone marrow transplant for leukemia in older adults. JAMA. 993;270:57–60.
  3. Weiden PL, Sullivan KM, Flournoy N, Storb R, Thomas ED. Antileukemic effect of chronic graft-versus-host disease: contribution to improved survival after allogeneic marrow transplantation. N Engl J Med. 1981;304:1529–1533
  4. Weiden PL, Flournoy N, Thomas ED, et al. Antileukemic effect of graft-versus-host disease in human recipients of allogeneic-marrow grafts. N Engl J Med. 1979;300:1068–1073
  5. Horowitz MM, Gale RP, Sondel PM, et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood. 1990;75:555–562
  6. Giralt S, Estey E, Albitar M, et al. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood. 1997;89:4531–4536
  7. Khouri IF, Keating M, Korbling M, et al. Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies. J Clin Oncol. 1998;16:2817–2824
  8. Slavin S, Nagler A, Naparstek E, et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood. 1998;91:756–763
  9. Sykes M, Preffer F, McAfee S, et al. Mixed lymphohaemopoietic chimerism and graft-versus-lymphoma effects after non-myeloablative therapy and HLA-mismatched bone-marrow transplantation. Lancet. 1999;353:1755–1759
  10. Carella AM, Cavaliere M, Lerma E, et al. Autografting followed by nonmyeloablative immunosuppressive chemotherapy and allogeneic peripheral-blood hematopoietic stem-cell transplantation as treatment of resistant Hodgkin's disease and non-Hodgkin's lymphoma. J Clin Oncol. 2000;18:3918–3924
  11. McSweeney PA, Niederwieser D, Shizuru JA, 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
  12. Giralt S, Thall PF, Khouri I, et al. Melphalan and purine analog-containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation. Blood. 2001;97:631–637
  13. Childs R, Chernoff A, Contentin N, et al. Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation. N Engl J Med. 2000;343:750–758
  14. Michallet M, Bilger K, Garban F, et al. Allogeneic hematopoietic stem-cell transplantation after nonmyeloablative preparative regimens: impact of pretransplantation and posttransplantation factors on outcome. J Clin Oncol. 2001;19:3340–3349
  15. Martino R, Caballero MD, Simon JA, et al. Evidence for a graft-versus-leukemia effect after allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning in acute myelogenous leukemia and myelodysplastic syndromes. Blood. 2002;100:2243–2245
  16. Mohty M, Bay JO, Faucher C, et al. Graft-versus-host disease following allogeneic transplantation from HLA-identical sibling with antithymocyte globulin-based reduced-intensity preparative regimen. Blood. 2003;102:470–476
  17. Hegenbart U, Niederwieser D, Sandmaier BM, et al. Treatment for acute myelogenous leukemia by low-dose, total-body, irradiation-based conditioning and hematopoietic cell transplantation from related and unrelated donors. J Clin Oncol. 2006;24:444–453
  18. Gail M. A review and critique of some models used in competing risk analysis. Biometrics. 1975;31:209–222
  19. Peto R, Pike MC, Armitage P, et al. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. Analysis and examples. Br J Cancer. 1977;35:1–39
  20. Martino R, Perez-Simon JA, Moreno E, et al. Reduced-intensity conditioning allogeneic blood stem cell transplantation with fludarabine and oral busulfan with or without pharmacokinetically targeted busulfan dosing in patients with myeloid leukemia ineligible for conventional conditioning. Biol Blood Marrow Transplant. 2005;11:437–447
  21. Barrett J. Improving outcome of allogeneic stem cell transplantation by immunomodulation of the early post-transplant environment. Curr Opin Immunol. 2006;18:592–598
  22. Nagler A, Aker M, Or R, et al. Low-intensity conditioning is sufficient to ensure engraftment in matched unrelated bone marrow transplantation. Exp Hematol. 2001;29:362–370
  23. Mohty M. Mechanisms of action of antithymocyte globulin: T-cell depletion and beyond. Leukemia. 2007;21:1387–1394
  24. Nakai K, Mineishi S, Kami M, et al. Antithymocyte globulin affects the occurrence of acute and chronic graft-versus-host disease after a reduced-intensity conditioning regimen by modulating mixed chimerism induction and immune reconstitution. Transplantation. 2003;75:2135–2143
  25. Bacigalupo A. Antithymocyte globulin for prevention of graft-versus-host disease. Curr Opin Hematol. 2005;12:457–462
  26. Alessandrino EP, Bernasconi P, Colombo AA, et al. Reduced-intensity conditioning regimen with thiotepa and fludarabine followed by allogeneic blood stem cell transplantation in haematological malignancies. Bone Marrow Transplant. 2004;34:1039–1045
  27. Bacigalupo A. Third EBMT/AMGEN Workshop on reduced-intensity conditioning allogeneic haemopoietic stem cell transplants (RIC-HSCT), and panel consensus. Bone Marrow Transplant. 2004;33:691–696
  28. Farag SS, Elder PJ, Marcucci G, et al. Radiation-free regimens result in similar outcomes of allogeneic hematopoietic progenitor cell transplantation in patients aged > or = 50 years compared to younger adults with low-risk disease. Bone Marrow Transplant. 2003;31:87–93
  29. Slavin S. Reduced intensity versus truly nonmyeloablative conditioning for stem-cell transplant recipients. Transplantation. 2004;78:964–965
  30. Alyea EP, Kim HT, Ho V, et al. Comparative outcome of nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation for patients older than 50 years of age. Blood. 2005;105:1810–1814
  31. Le Blanc K, Remberger M, Uzunel M, Mattsson J, Barkholt L, Ringden O. A comparison of nonmyeloablative and reduced-intensity conditioning for allogeneic stem-cell transplantation. Transplantation. 2004;78:1014–1020
  32. Valcarcel D, Martino R, Sureda A, 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
  33. Blaise D, Vey N, Faucher C, Mohty M. Current status of reduced intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia. Haematologica. 2007;92:533–541
  34. Khouri IF, Saliba RM, Giralt SA, et al. Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality. Blood. 2001;98:3595–3599
  35. Dreger P, Brand R, Hansz J, et al. Treatment-related mortality and graft-versus-leukemia activity after allogeneic stem cell transplantation for chronic lymphocytic leukemia using intensity-reduced conditioning. Leukemia. 2003;17:841–848
  36. Schetelig J, Thiede C, Bornhauser M, et al. Evidence of a graft-versus-leukemia effect in chronic lymphocytic leukemia after reduced-intensity conditioning and allogeneic stem-cell transplantation: the Cooperative German Transplant Study Group. J Clin Oncol. 2003;21:2747–2753
  37. Corradini P, Dodero A, Zallio F, 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
  38. Sureda A, Schmitz N. Allogeneic stem cell transplantation after reduced-intensity conditioning in lymphoid malignancies. Ann Hematol. 2003;82:1–13
  39. Atkinson K, Horowitz MM, Gale RP, et al. Risk factors for chronic graft-versus-host disease after HLA-identical sibling bone marrow transplantation. Blood. 1990;75:2459–2464
  40. Brown RA, Adkins D, Khoury H, et al. Long-term follow-up of high-risk allogeneic peripheral-blood stem-cell transplant recipients: graft-versus-host disease and transplant-related mortality. J Clin Oncol. 1999;17:806–812
  41. Perez-Simon JA, Diez-Campelo M, Martino R, et al. Impact of CD34+ cell dose on the outcome of patients undergoing reduced-intensity-conditioning allogeneic peripheral blood stem cell transplantation. Blood. 2003;102:1108–1113
  42. Mohty M, Bagattini S, Chabannon C, et al. CD8+ T cell dose affects development of acute graft-vs-host disease following reduced-intensity conditioning allogeneic peripheral blood stem cell transplantation. Exp Hematol. 2004;32:1097–1102
  43. Worel N, Kalhs P, Keil F, et al. ABO mismatch increases transplant-related morbidity and mortality in patients given nonmyeloablative allogeneic HPC transplantation. Transfusion. 2003;43:1153–1161
  44. Seebach JD, Stussi G, Passweg JR, et al. ABO blood group barrier in allogeneic bone marrow transplantation revisited. Biol Blood Marrow Transplant. 2005;11:1006–1013

PII: S0301-472X(08)00053-2

doi: 10.1016/j.exphem.2008.01.017

Experimental Hematology
Volume 36, Issue 5 , Pages 535-544 , May 2008