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Nonmyeloablative Allogeneic Transplantation

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Allogeneic Stem Cell Transplantation

Part of the book series: Current Clinical Oncology ((CCO))

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Abstract

High doses of chemotherapy and radiation, combined with a new immune system generated by an allogeneic hematopoietic stem cell transplant, have significant potential benefits for the treatment of multiple types of illnesses, as outlined throughout this text. Unfortunately, the majority of patients are not candidates for this approach. This chapter will discuss a shift in the understanding of the requirements for successful allogeneic hematopoietic transplantation, allowing for less toxic preparative regimens while maintaining reliable donor engraft-ment. Successful exploitation of this approach will allow older, more debilitated patients to undergo allogeneic immunotherapy in the future. Further, if the risks are truly decreased, the cost—benefit ratio may be sufficiently shifted to allow new diseases to be targeted for therapy, such as patients with hemoglobinopathies, selected genetic deficits, or autoimmune illnesses.

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References

  1. Keil F, Kalhs P, Haas 0, et al. Relapse of Philadelphia chromosome positive acute lymphoblastic leukemia after marrow transplantation: sustained molecular remission after early and dose-escalating infusion of donor leukocytes. Br J Haematol 1997; 97: 161–164.

    Article  PubMed  CAS  Google Scholar 

  2. Gurman G, Arslan O, Koc H, et al. Donor leukocyte infusion for relapsed ANLL after allogeneic BMT and the use of interferon alpha to induce graft versus leukemia effect. Bone Marrow Transplant 1996; 18: 825, 826.

    Google Scholar 

  3. Odom L, August C, Githens J, et al. Remission of relapsed leukemia during a graft versus host reaction. Lancet 1978; 2: 537–540.

    Article  PubMed  CAS  Google Scholar 

  4. Drobyski W, Keever C, Roth M, et al. Salvage immunotherapy using donor leukocyte infusions as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation: effficacy and toxicity of a defined T cell dose. Blood 1993; 82: 2310–2318.

    PubMed  CAS  Google Scholar 

  5. Weiden P, Flournoy N, Thomas E, et al. Antileukemic effect of graft versus host disease in human recipients of allogeneic marrow grafts. NEngl JMed 1979; 300: 1068–1073.

    Article  CAS  Google Scholar 

  6. Sullivan K, Weiden P, 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.

    PubMed  CAS  Google Scholar 

  7. Horowitz M, Gale R, Sondel P, et al. Graft versus leukemia reactions after bone marrow transplantation. Blood 1990; 75: 555–562.

    PubMed  CAS  Google Scholar 

  8. Anichini A, Mortarini R, Maccalli C, et al. Cytotoxic T cells directed to tumor antigens not expressed on normal melanocytes dominate HLA-A2.1- restricted immune repertoire to melanoma. Jlmmunol 1996; 156: 208–217.

    CAS  Google Scholar 

  9. Dadmarz R, Sgagias N, Rosenberg S, et al. CD4+ T lymphocytes infiltrating human breast cancer recognise autologous tumor in an MHC class II restricted fashion. Cancer Immunol Immunother 1995; 40: 1–9.

    PubMed  CAS  Google Scholar 

  10. Rocha M, Umansky V, Lee KH, et al. Differences between graft-versus-leukemia and graft-versus-host reactivity. I. Interaction of donor immune T cells with tumor and/or host cells. Blood 1997; 89: 2189–2202.

    PubMed  CAS  Google Scholar 

  11. Eibl B, S chwaighoferH, Nachbaur D, et al. Petersen F, Niederwieser D. Evidence for a graft versus tumor effect in a patient treated with marrow ablative chemotherapy and allogeneic bone marrow transplantation for breast cancer. Blood 1996; 88: 1501–1508.

    PubMed  CAS  Google Scholar 

  12. Mehta J, Powles R, Treleaven J, et al. Long term follow up of patients undergoing allogeneic transplantation for acute myeloid leukemia in first remission after cyclophosphamide-total body irradiation and cyclosporine. Bone Marrow Transplant 1996;18:741–746,.

    Google Scholar 

  13. Bradley J, Reft C, Goldman S, Rubin C, Nachman J, Larson R, Hallahan DE. High energy total body irradiation as preparation for bone marrow transplantation in leukemia patients: treatment technique and related complication.s Int J Radiat Oncol Biol Phys 1998; 40: 391–396.

    Article  PubMed  CAS  Google Scholar 

  14. Reddy V, Pollock BH, Sharda A, et al. GVHD and CMV antigenemia after allogeneic peripheral blood stem cell transplantation: comparison between myeloablative and nonmyeloablative conditioning regimens. Blood 2000; 96 (Suppl 1): 817.

    Google Scholar 

  15. Storb R, Raff RF, Appelbaum FR, et al. Comparison of fractionated to single-dose total body irradiation in conditioning canine littermates for DLA-identical marrow grafts. Blood 1989; 74: 1139–1143.

    PubMed  CAS  Google Scholar 

  16. Yu C, Sandmaier BM, Deeg HJ, Storb R. What role for radiation in novel nonmyeloablative transplant regimen for DLA-identical marrow grafts: Immunosuppression versus `creation’ of marrow space?Blood 1997; 90 (Suppl 1): 1608.

    Google Scholar 

  17. Yu C, Storb R, Mathey B, et al. DLA identical bone marrow grafts after low dose total body irradiation effects of high dose corticosteroids and cyclosporine on engraftment. Blood 1995; 86: 4376–4381.

    PubMed  CAS  Google Scholar 

  18. Storb R, Yu Cong, Wagner J, et al. Stable mixed hematopoietic chimerism in DLA Identical littermate dogs given sublethal total body irradiation before pharmacological immunosuppression after marrow transplantation. Blood 1997; 89: 3048–3054.

    PubMed  CAS  Google Scholar 

  19. Yu C, Seidel K, Nash RA, et al. Synergism between mycophenylate mofetil and cyclosporine in preventing graft vrsus host disease among lethally irradiated dogs given DLA-non identical unrelated marrow grafts. Blood 1998; 91: 2581–2587.

    PubMed  CAS  Google Scholar 

  20. Stewart FM, Zhong S, Wuu J, et al. Lymphohematopoietic engraftment in minimally myeloablated hosts. Blood 1998; 91: 3681–3687.

    PubMed  CAS  Google Scholar 

  21. Giralt S, Estey E, Albitar M, et al. Engraftment of allogeneic porgenitor cells with purine analog-containing chemotherapy: harnessing graft versus leukemia without myeloablative therapy. Blood 1997; 89: 4531–4536.

    PubMed  CAS  Google Scholar 

  22. Maris MB, Sandmaier BM, Niederwieser D, et al. Comparisons of donor chimerism, graft rejection, and GVHD after hematopoietic stem cell transplants from HLA matched siblings and unrelated donors using conditioning with 2 Gy TBI with and without fludarabine. Blood 2000; 96 (Suppl 1): 2239.

    Google Scholar 

  23. Khouri I, Keating MJ, Przepiorka D, et al. Engraftment and induction of GVL with fludarabine (FAMP)-based non-ablative preparative regimen in patients with chronic lymphocytic leukemia (CLL) and lymphoma. Proc ASH Blood 1996; 301A: 1194.

    Google Scholar 

  24. Khouri IF, Keating M, Korbling M, et al. Transplant lite: induction of graft versus malignancy using fludarabinebased nonablative chemotherapy and allogeneic blood progenitor cell transplantation as treatment for lymphoid malignancies. J Clin Oncol 1998; 16: 2817 2824.

    Google Scholar 

  25. Giralt S, Weber D, Aleman A, et al. Non-myeloablative conditioning with fludarabine/melphalan for patients with multiple myeloma. Blood 1999; 94 (Suppl 1): 1549.

    Google Scholar 

  26. Alcindor T, Chan G, Al-Olama A, et al. Engraftment and immunologic effects of a novel less myeloablative allogeneic transplant conditioning regimen of continuous infusion pentostatin, photopheresis, and low dose TBI. Blood 2000; 96 (Suppl 1): 5160.

    Google Scholar 

  27. Molina A, Sahebi F, Maloney DG, et al. Nonmyeloablative peripheral blood stem cell allografts following cytoreductive autotransplants for the treatment of multiple myeloma. Blood 2000; 96 (Suppl 1): 2063.

    Google Scholar 

  28. 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 non-malignant hematologic diseases. Blood 1998; 91: 756–763.

    PubMed  CAS  Google Scholar 

  29. GarbanF, Attal M, Rossi JF, S otto JJ. High efficiency of non myeloablative allogeneic stem cell transplantation in poor prognosis myeloma patients. Blood 1999; 94 (Suppl 1): 1550.

    Google Scholar 

  30. Faucher C, Mohty M, Vey N, et al. Allogeneic BMT with nonmyeloablative regimen: early full donor chimer-ism and increased rate of infections. Blood 1999; 94 (Suppl 1): 654.

    Google Scholar 

  31. Carella AM, Corsetti MT, Lerma E, Cavaliere M. Auologous transplants followed by mini allografts for hodgkin’s disease and non hodgkin’s lymphoma. Blood 2000; 96 (Suppl 1): 1752.

    Google Scholar 

  32. Badros A, Tricot G, Morris C, et al. Significant graft versus myeloma effect after nonmyeloablative allogeneic transplantation in multiple myeloma. Blood 2000; 96 (Suppl 1): 5273.

    Google Scholar 

  33. Couriel D, Giralt S, De Lima M, et al. Graft versus host disease after non-myeloablative versus ablative conditioning regimens in fully matched sibling donorhematopoietic stem cell transplants. Blood2000; 96 (Suppl 1): 1758.

    Google Scholar 

  34. Schwaighofer H, Kernan NA, O’Reilly RJ, et al. Serum levels of cytokines and secondary messages after Tcell-depleted and non-T-cell-depleted bone marrow transplantation: influence of conditioning and hematopoietic reconstitution. Transplantation 1996; 62: 947–953.

    Article  PubMed  CAS  Google Scholar 

  35. Weiss L, Lubin I, Factorowich I, et al. Effective graft-versus-leukemia effects independent of graft-versus-host disease after T cell-depleted allogeneic bone marrow transplantation in a murine model of B cell leukemia/ lymphoma. Role of cell therapy and recombinant IL-2. J Immunol 1994; 153: 2562–2567, 1994.

    Google Scholar 

  36. Long GW, Laughlin MJ, Madan B, et al. Unrelated umbilical cord blood transplantation in adult patients. Blood 2001; accepted.

    Google Scholar 

  37. Laughlin MJ, Barker J, Bambach B, et al. Hematopoietic engraftment ans survival after unrelated donor umbilical cord blood transplant in adult recipients. N Engl J Med 2001;344(24): 1815–1822, 2001.

    Google Scholar 

  38. Spitzer TR, McAfee SL, Sackstein R, et al. Induction of mixed chimerism and potent anti-tumor responses following mon-myeloablative conditioning therapy and HLA-matched and mismatched donor bone marrow transplantation for refractory hematologic malignancies. Blood 1998; 92: 519a.

    Google Scholar 

  39. Osterborg A, Fassas A, Anagostopoulos A, et al. Humanized CD52 monoclonal antibody Campath-1H as frontline treatment in chronic lymphocytic leukemia. Br J Hematol 1996: 93; 151–153.

    Article  CAS  Google Scholar 

  40. Dyer M, Kelsey S, Mackey H, et al. In vivo `purging’ of residual disease in CLL with Campath-1H. Br J Heamtol 1997; 97: 669–672.

    Article  CAS  Google Scholar 

  41. Osterborg A, Dyer M, Bunjes D, et al. Phase II multicenter study of human CD52 antibody in previously treated chronic lymphocyte leukemia. J Clin Oncol 1997; 15: 1567–1574.

    PubMed  CAS  Google Scholar 

  42. Hale G, Waldmann H. Control of graft-versus-host disease and graft rejection by T-cell depletion of donor and recipient with Campath-1H antibodies. Results of matched sibling transplants for malignant diseases. Bone Marrow Transplant 1994; 13: 597–611.

    PubMed  CAS  Google Scholar 

  43. Hertenstein B, Arseniev L, Bötel V, Hale J. Abstract. 2d International Symposium on Allogeneic Peripheral Blood and Cord Blood Transplantation. Geneva, Switzerland. October 30-November 1997, p. 36.

    Google Scholar 

  44. Hale G, Waldmann H. CAMPATH User’ s Group. Risks of developing EBV-related lymphoproliferative disorders following T cell depleted marrow transplants. Blood 1998; 91: 3079–3083.

    Google Scholar 

  45. Hale G, Zhang MJ, Bunjes D, et al. Improving the outcome of bone marrow transplantation by using CD52 monoclonal antibodies to prevent graft versus host disease and graft rejection. Blood 1998; 92: 4581–4590.

    PubMed  CAS  Google Scholar 

  46. Reittie E, Gottlieb D, Heslop H, et al. Brenner MK. Endogenously generated activated killer cells circulate after autologous and allogeneic transplantation but not after chemotherapy. Blood 1989; 73: 1351–1358.

    PubMed  CAS  Google Scholar 

  47. Russell NH, Cull G, Byrne IL, et al. Evaluation of non-myeloablative conditioning combining BEAM with in vivo pre-transplant CAMPATH 1G for allogeneic transplantation in patients with lymphoma. Blood 1999; 94 (Suppl 1): 1554.

    Google Scholar 

  48. Craddock C, Hughes T, Johnston R, et al. Engraftment of T depleted allogeneic peripheral blood stem cells using a non myeloablative conditioning regimen. Blood 1999; 94 (Suppl 1): 1746.

    Google Scholar 

  49. Chakrabarti S, Steven N, Collingham K, et al. Viral reactivation and immune reconstitution following CAMPATH 1H and fludarabine based non-myeloablative conditioning for allogeneic stem cell transplantation compared to CAMPATH bsed T cell depletion regimens: a preliminary report. Blood 1999; 94 (Suppl 1): 668.

    Google Scholar 

  50. Rizzieri DA, Long GD, Vredenburgh J, et al. Chimerism mediated immunotherapy using CAMPATH T cell depleted peripheral blood ptogenitor cells with nonablative therapy provides reliable, durable, allogeneic engraftment. Blood 2000; 96 (Suppl 1): 2241.

    Google Scholar 

  51. Aversa F, Tabilio A, Velardi A, et al. Treatment of high risk acute leukemia with T cell depleted stem cells from related donors with one fully mismatched HLA haplotype. N Engl J Med 1998; 339: 1186–1193.

    Article  PubMed  CAS  Google Scholar 

  52. Bornhauser M, Neubauer A, Thiede C, et al. Allogeneic blood stem cell transplants from unrelated donors after nonablative conditioning therapy. Blood 1998; 92 (Suppl 1): 4530.

    Google Scholar 

  53. Schetelig J, Held T, Bornhauser M, et al. Nonmyeloablative allogeneic stem cell transplantation in chronic lymphocytic leukemia from related and unrelated donors. Blood 2000; 96 (Suppl 1): 857.

    Google Scholar 

  54. Peggs KS, Mahendra P, Milligan DW, et al. Non myeloablatvie transplantation using matche dunrelated donors-in vivo campath 1H limits graft versus host disease.

    Google Scholar 

  55. Nagler A, Or R, Varadig, Shapira M, Slavin S. Fludarabine based low intensity conditioning protocol for unrelated matched stem cell transplantation in chronic myelogenous leukemia. Blood 2000; 96 (Suppl 1): 5322.

    Google Scholar 

  56. Nagler A, Or R, Naparstek E, et al. A non-myeloablative regimen may suffice for engraftment of allogeneic mismatched related stem cell transplantation but not of unrelated bone marrow transplantation with a similar degree of HLA mismatch. Blood 1998; 92 (Suppl 1): 2815.

    Google Scholar 

  57. Rizzieri DA, Long GD, Vredenburgh JJ, et al. Successful allogeneic engraftment of mismatched unrelated cord blood following a non-myeloablative preparative regimen. Blood 2001; 98: 3486–3488.

    Article  PubMed  CAS  Google Scholar 

  58. Ueno N, Rondon G, Mirza N, et al. Allogeneic peripheral blood progenitor cell transplantation for poor risk patients with metastatic breast cancer. J Clin Oncol 1998; 16: 986–993.

    PubMed  CAS  Google Scholar 

  59. Childs RW, Clave E, Tisdale J, et al. Successful treatment of metastatic renal cell carcinoma with a nonmyeloablative allogeneic peripheral blood progenitor cell transplant: evidence for a graft versus tumor effect. J Clin Oncol 1999; 17: 2044–2049.

    PubMed  CAS  Google Scholar 

  60. Childs R, Bahceci E, Clave E, et al. Non-myeloablative peripheral blood stem cell transplants for malignant disease reduces transplant related mortality. Blood 1998; 92 (Supp 1): 552.

    Google Scholar 

  61. 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.

    Article  PubMed  CAS  Google Scholar 

  62. Seong C, Lee S, Im S, et al. HLA identical peripheral blood progrenitor cells transplantation for metastatic gastric carcinoma using non-myeloablative conditioning regimen. Blood 1998; 92 (Suppl 1): 4270.

    Google Scholar 

  63. Childs RW, Bradstock KF, Gottlieb D, et al. Non-myeloablative allogeneic stem cell transplantation as immunotherapy for metastatic melanoma: results of a pilot study. Blood 2000; 96 (Suppl 1): 5277.

    Google Scholar 

  64. Woolfrey A, Nash R, Frangoul H, et al. Non-myeloablative transplant regimen used for induction of multi lineage allogeneic hematopoietic mixed donor-host chimerism in patients with T cell immunodeficiency. Blood 1998; 92 (Suppl 1): 2135.

    Google Scholar 

  65. Walters MC, Patience M, Leisenring W, et al. Collaborative multicenter investigation of marrow transplantation for sickle cell disease: current results and future directions. Biol Blood Marrow Transplant 1997; 3: 310–315.

    PubMed  CAS  Google Scholar 

  66. Lucarelli G, Clift RA, Galimberti M, et al. Marrow transplantation for patients with thalassemia: results in class 3 patients. Blood 1996; 87: 2082–2088.

    PubMed  CAS  Google Scholar 

  67. Krishnamurti L, Blazer B, Grossi M, et al. Successful use of non-myeloablative therapy in the treatment of severe hemoglobinopathies: proof of principle. Blood 2000; 96 (Suppl 1): 3734.

    Google Scholar 

  68. Toh HC, Preffer F, Spitzer TR, et al. Characterization of phenotypic and functional lymphocyte reconstitution in adult patients with chemoradiorefractory hematologic malignancies receiving a non-myeloablative conditioning therapy and HLA matched and mismatched donor bone marrow transplantation. Blood 1998; 92 (Suppl 1): 2818.

    Google Scholar 

  69. Bahceci E, Epperson D, Patibandla A, et al. Rapid reconstitution of T cell compartment after non-myeloablative allogeneic stem cell transplantation. Blood 1999; 94 (Suppl 1): 590.

    Google Scholar 

  70. Childs R, Clave E, Contentin N, et al. Engraftment kinetics after nonmyeloablative allogeneic peripheral blood stem cell transplantation: full donor T cell chimerism preceded alloimmune responses. Blood 1999; 94: 3234–3241.

    PubMed  CAS  Google Scholar 

  71. KeilF, Kalhs P, Haas O, et al. Relapse of Philadelphia chromosome positive acute lymphoblastic leukemia after marrow transplantation: sustained molecular remission after early and dose-escalating infusion of donor leukocytes. Br J Haematol 1997; 97: 161–164.

    Article  PubMed  Google Scholar 

  72. Ruggeri L, Capanni M, Urbani E, et al. KIR epitope incompatibility in th eGvH direction predicts control of leukemia relapse after mismatched hematopoietic transplantation. Blood 2000; 96 (Suppl 1): 2059.

    Google Scholar 

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Authors
  1. David A. Rizzieri MD
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  2. Nelson J. Chao MD
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Editor information

Editors and Affiliations

  1. Allogeneic Transplant Program, Ireland Cancer Center, University Hospitals of Cleveland, Case Western Reserve University, Cleveland, OH, USA

    Mary J. Laughlin MD

  2. Blood and Marrow Transplant Program, Ireland Cancer Center, University Hospitals of Cleveland, Case Western Reserve University, Cleveland, OH, USA

    Hillard M. Lazarus MD

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Rizzieri, D.A., Chao, N.J. (2003). Nonmyeloablative Allogeneic Transplantation. In: Laughlin, M.J., Lazarus, H.M. (eds) Allogeneic Stem Cell Transplantation. Current Clinical Oncology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-333-0_13

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  • DOI: https://doi.org/10.1007/978-1-59259-333-0_13

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4757-4481-1

  • Online ISBN: 978-1-59259-333-0

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