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Allografting

Reduced-intensity allogeneic haemopoietic stem cell transplantation induces durable responses in patients with chronic B-lymphoproliferative disorders

Bone Marrow Transplantation volume 37, pages 923–928 (2006)Cite this article

Abstract

Thirty-six patients with chronic B-lymphoproliferative disorders (B-LPD) underwent reduced-intensity allogeneic transplantation (RIT) from HLA-identical related donors. Diagnoses included follicular (n=17), mantle cell (n=9) and small lymphocytic lymphoma (n=2), and chronic lymphocytic leukaemia (n=8). Median age at transplant was 51 years (range, 30–66) and time from diagnosis was 3.4 years (range, 0.3–9.5). At transplant, 28% were in CR, 36% were in PR and 36% were chemorefractory. Conditioning therapy included fludarabine and either cyclophosphamide (n=27) or melphalan (n=9). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin (CsA)/methotrexate (n=21), CsA/mycophenolate mofetil (n=13) or CsA alone (n=2). Eight patients died owing to acute GVHD (n=3), infection in association with chronic GVHD (n=4) and intra-abdominal bleeding (n=1). Treatment-related mortality was 8% at day 100, and 17 and 20% at one and two years, respectively. The cumulative incidence of grade II–IV acute GVHD was 58%, whereas limited and extensive chronic GVHD occurred in 25 and 56%, respectively. No patient has relapsed or progressed. At a median follow-up of 48 months, overall survival probability is 80% (95% CI, 67–93%). We confirm that RIT in chronic B-LPD can result in high and durable CR rates but with significant incidences of acute and chronic GVHD.

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References

  1. van Besien K, Sobocinski KA, Rowlings PA, Murphy SC, Armitage JO, Bishop MR et al. Allogeneic bone marrow transplantation for low grade lymphoma. Blood 1998; 92: 1832–1836.

    CAS  PubMed  Google Scholar 

  2. Peniket AJ, Ruiz DEM, Taghipour G, Cordonnier C, Gluckman E, de Witte T et al. An EBMT registry matched study of allogeneic stem cell transplants for lymphoma: allogeneic transplantation is associated with a lower relapse rate but a higher procedure-related mortality rate than autologous transplantation. Bone Marrow Transplant 2003; 31: 667–678.

    Article  CAS  PubMed  Google Scholar 

  3. Van Besien K, Loberiza FRJ, Bajorunaite R, Armitage JO, Bashey A, Burns LJ et al. Comparison of autologous and allogeneic hematopoietic stem cell transplantation for follicular lymphoma. Blood 2003; 102: 3521–3529.

    Article  CAS  PubMed  Google Scholar 

  4. Freytes CO, Loberiza FR, Rizzo JD, Bashey A, Bredeson CN, Cairo MS et al. Myeloablative allogeneic hematopoietic stem cell transplantation in patients who experience relapse after autologous stem cell transplantation for lymphoma: a report of the International Bone Marrow Transplant Registry. Blood 2004; 104: 3797–3803.

    Article  CAS  PubMed  Google Scholar 

  5. Diaconescu R, Flowers CR, Storer B, Sorror ML, Maris MB, Maloney DG et al. Morbidity and mortality with nonmyeloblative compared with myeloablative conditioning before hematopoietic cell transplantation from HLA-matched related donors. Blood 2004; 104: 1550–1558.

    Article  CAS  PubMed  Google Scholar 

  6. 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-host tumor effects. Blood 2001; 97: 3390–3400.

    Article  CAS  PubMed  Google Scholar 

  7. Corradini P, Tarella A, Olivieri A, Gianni AM, Voena C, Zallio F et al. Reduced-intensity conditioning followed by allografting of hematopoietic cells can produce clinical and molecular remissions in patients with poor-risk hematologic malignancies. Blood 2002; 99: 75–82.

    Article  CAS  PubMed  Google Scholar 

  8. 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 

  9. Alyea EP, Kim HT, Ho V, Cutler C, Gribben J, DeAngelo DJ 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.

    Article  CAS  PubMed  Google Scholar 

  10. Collins Jr RH, Shpilberg O, Drobyski WR, Porter DL, Giralt S, Champlin R et al. Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J Clin Oncol 1997; 15: 433–444.

    Article  PubMed  Google Scholar 

  11. Kolb HJ, Schattenberg A, Goldman JA, Hertenstein B, Jacobson N, Arcese W et al. Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. Blood 1995; 86: 2041–2050.

    CAS  PubMed  Google Scholar 

  12. van Besien KW, de Lima M, Giralt SA, Moore Jr DF, Khouri IF, Rondon G et al. Management of lymphoma recurrence after allogeneic transplantation: the relevance of graft-versus-lymphoma effect. Bone Marrow Transplant 1997; 19: 977–982.

    Article  CAS  PubMed  Google Scholar 

  13. Champlin R, Khouri I, Shimoni A, Gajewski J, Kornblau S, Molldrem J et al. Harnessing graft-versus-malignancy: non-myeloablative preparative regimens for allogeneic haematopoietic transplantation, an evolving strategy for adoptive immunotherapy. Br J Haematol 2000; 111: 18–29.

    Article  CAS  PubMed  Google Scholar 

  14. Slavin S, Nagler A, Naparstek E, Kapelushnik Y, Aker M, Cividalli G 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 non-malignant hematologic diseases. Blood 1998; 91: 756–763.

    CAS  PubMed  Google Scholar 

  15. Giralt S, Estey E, Albitar M, van Besien K, Rondon G, Anderlini P 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.

    CAS  PubMed  Google Scholar 

  16. Giralt S, Thall PF, Khouri I, Wang X, Braunschweig I, Ippolitti C et al. Melphalan and purine-analog-containing regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation. Blood 2001; 97: 631–637.

    Article  CAS  PubMed  Google Scholar 

  17. Robinson SP, Goldstone AH, Mackinnon S, Carella A, Russell N, Ruiz de Elvira C 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 

  18. Alessandrino EP, Bernasconi P, Colombo AA, Caldera D, Malcovati L, Troletti D 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.

    Article  CAS  PubMed  Google Scholar 

  19. Kottaridis PD, Milligan DW, Chopra R, Chakfaverty RK, Chakrabarti S, Robinson S et al. In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation. Blood 2000; 96: 2419–2425.

    CAS  PubMed  Google Scholar 

  20. Perez-Simon JA, Kottaridis PD, Martino R, Craddock C, Cabellero D, Chopra R et al. Nonmyeloablative transplantation with or without alemtuzumab: comparison between 2 prospective studies in patients with lymphoproliferative disorders. Blood 2002; 100: 3121–3127.

    Article  CAS  PubMed  Google Scholar 

  21. Morris E, Thomson K, Craddock C, Mahendra P, Milligan D, Cook G et al. Outcomes after alemtuzumab-containing reduced-intensity allogeneic transplantation regimen for relapsed and refractory non-Hodgkin lymphoma. Blood 2004; 104: 3865–3871.

    Article  CAS  PubMed  Google Scholar 

  22. Grigg A, Ritchie D . Graft-versus-lymphoma effects: clinical review, policy proposals, and immunobiology. Biol Blood Marrow Transplant 2004; 10: 579–590.

    Article  CAS  PubMed  Google Scholar 

  23. Escalon MP, Champlin R, Saliba RM, Acholonu SA, Hosing C, Fayad L et al. Nonmyeloablative allogeneic hematopoietic transplantation: a promising salvage therapy for patients with non-Hodgkin's lymphoma whose disease has failed a prior autologous transplantation. J Clin Oncol 2004; 22: 2419–2423.

    Article  PubMed  Google Scholar 

  24. Khouri IF, Saliba RM, Giralt S, Lee MS, Okoroji GJ, Hagemeister FB 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.

    Article  CAS  PubMed  Google Scholar 

  25. Tanimoto TE, Kusumi E, Hamaki T, Yuji K, Ueyama J, Miyakoshi S et al. High complete response rate after allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning regimens in advanced malignant lymphoma. Bone Marrow Transplant 2003; 32: 131–137.

    Article  CAS  PubMed  Google Scholar 

  26. Nagler A, Slavin S, Varadi G, Naparsetk E, Samuel S, Or R . Allogeneic peripheral blood stem cell transplantation using a fludarabine based low intensity conditioning regimen for malignant lymphomas. Bone Marrow Transplant 2000; 25: 1021–1028.

    Article  CAS  PubMed  Google Scholar 

  27. Corradini P, Dodero A, Bregni M, Olivieri A, Farina L, Rizzo E et al. Reduced-intensity conditioning (RIC) followed by allogeneic transplantation in relapsed lymphomas: evidence for graft-versus-lymphoma effect in low and high grade histologies, but not in Hodgkin disease. Blood 2004; 104: 230a (abstract).

    Google Scholar 

  28. Maris MB, Sandmaier B, 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 

  29. Bowell B, Sobecks R, Pohlman B, Andresen S, Rybicki L, Kuczkowski E et al. A prospective randomised 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  Google Scholar 

  30. 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 2025; 35: 1089–1093.

    Article  Google Scholar 

  31. Khouri IF, Lee MS, Saliba RM, Jun G, Fayad L, Younes A et al. Nonablative allogeneic stem-cell transplantation for advanced/recurrent mantle cell lymphoma. J Clin Oncol 2003; 21: 4407–4412.

    Article  CAS  PubMed  Google Scholar 

  32. Dreger P, Brand R, Milligan D, Corradini P, Finke J, Lambertenghi Deliliers G et al. Treatment-related mortality and graft-versus leukemia activity after allogeneic stem cell transplantation for chronic lymphocytic leukemia using reduced-intensity conditioning. Leukemia 203; 17: 841–848.

    Article  Google Scholar 

  33. Schetelig J, Thiede C, Bornhauser M, Schwerdtfeger R, Kiehl M, Beyer J et al. Evidence of a graft-versus-leukemia effect in chronic lymphocytic leukemia after reduced-intensity conditioning and allogeneic stem-cell transplantation. The Co-operative German Transplant Study Group. J Clin Oncol 2003; 21: 2747–2753.

    Article  CAS  PubMed  Google Scholar 

  34. Sorror ML, Maris MB, Sandmaier BM, Storer BE, Stuart MJ, Hegenbart U et al. Hematopoietic cell transplantation after nonmyeloablative conditioning for advanced chronic lymphocytic leukemia. J Clin Oncol 2005; 16: 3819–3829.

    Article  Google Scholar 

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Acknowledgements

We thank Karen Byth Wilson for statistical analysis.

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Authors and Affiliations

  1. Department of Haematology, BMT Service, Westmead Hospital, Westmead, New South Wales, Australia

    M Hertzberg, D Gottlieb, G Huang & K F Bradstock

  2. BMT Service, Royal Melbourne Hospital, Parkville, Victoria, Australia

    A Grigg, J Szer, A Roberts & R Hoyt

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  1. M Hertzberg
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Correspondence to M Hertzberg.

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Hertzberg, M., Grigg, A., Gottlieb, D. et al. Reduced-intensity allogeneic haemopoietic stem cell transplantation induces durable responses in patients with chronic B-lymphoproliferative disorders. Bone Marrow Transplant 37, 923–928 (2006). https://doi.org/10.1038/sj.bmt.1705357

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