Advertisement

International Journal of Hematology

, Volume 78, Issue 3, pp 195–207 | Cite as

Graft-versus-Host Disease, the Graft-versus-Leukemia Effect, and Mixed Chimerism following Nonmyeloablative Stem Cell Transplantation

  • Shimon Slavin
Progress in Hematology

Abstract

Allogeneic bone marrow or blood stem cell transplantation represents an important therapeutic tool for the treatment of otherwise incurable cancer and a large spectrum of nonmalignant diseases. Until recently, bone marrow transplantation was used primarily to eliminate malignant, genetically abnormal, or otherwise deficient stem cells; hence, highly toxic myeloablative regimens were considered mandatory for the eradication of undesirable cells of host origin. Recent data suggest that high-dose chemoradiotherapy may be successively replaced by nonmyeloablative stem cell transplantation (NST), which represents a safer biologic tool that involves the induction of host-versus-graft transplantation tolerance. NST thus provides allogeneic donor lymphocytes with the capacity to induce immune-mediated graft-versus-malignancy effects, either against mismatched minor or major histocompatibility alloantigens or against tumor-specific or tumor-associated antigens expressed by tumor or other hematologic cells of host origin. The future goals of the wider and safer clinical application of NST for the treatment of a larger number of indications and larger numbers of patients in need depend, on the one hand, on the development of more effective and safer modalities for maximizing the antitumor potential of donor lymphocytes (T-cells as well as natural killer and natural killer T-cells). On the other hand, these goals depend on using more selective approaches for targeting anticancer effector cells to their target cells. Such changes will thus set the stage for smarter rather than stronger modalities for the treatment of malignant and life-threatening nonmalignant diseases.Int J Hematol. 2003;78:195-207.

Key words

Stem cell transplantation Graft-versus-host disease Graft-versus-leukemia effects Graft-versus-tumor effects Nonmyeloablative stem cell transplantation Donor lymphocyte infusion Transplantation tolerance Mixed chimerism 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Thomas ED. Marrow transplantation for malignant diseases.J Clin Oncol. 1983;1:517–531.CrossRefPubMedGoogle Scholar
  2. 2.
    Gratwohl A, Hermans J, Goldman JM, et al. Risk assessment for patients with chronic myeloid leukaemia before allogeneic blood or marrow transplantation: Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation.Lancet. 1998;352:1087–1092.CrossRefPubMedCentralPubMedGoogle Scholar
  3. 3.
    Passweg JR, Rowlings PA, Armitage JO, et al. Report from the International Bone Marrow Transplant Registry and Autologous Blood and Marrow Transplant Registry: North America. In: Cecka JM, Teraskaki PI, eds.Clinical Transplants, 1995. Los Angeles, Calif: UCLA Tissue Typing Laboratory; 1996:117–127.Google Scholar
  4. 4.
    Bast CR. Principles of cancer biology: tumour immunology. In: DeVitta VT, Hellman S, Rosenberg SA, eds.Cancer: Principles and Practice of Oncology. Philadelphia, Pa: J. B. Lippincott; 1985:125–141.Google Scholar
  5. 5.
    Weiss L, Lubin I, Factorowich Y, 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.PubMedGoogle Scholar
  6. 6.
    Grillo-Lopez AJ, White CA, Dallaire BK, et al. Rituximab: the first monoclonal antibody approved for the treatment of lymphoma.Curr Pharm Biotechnol. 2000;1:1–9.CrossRefPubMedGoogle Scholar
  7. 7.
    Thomas ED. The role of marrow transplantation in the eradication of malignant disease.Cancer. 1963;49:1963–1968.CrossRefGoogle Scholar
  8. 8.
    Weiden PL, Sullivan KM, Fluornoy 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.CrossRefPubMedCentralPubMedGoogle Scholar
  9. 9.
    Weiden PL, Fluornoy N, Sanders JE, Sullivan KM, Thomas ED. Antileukemic effect of graft-versus-host disease contributes to improved survival after allogeneic marrow transplantation.Transplantation. 1981;13:248–251.Google Scholar
  10. 10.
    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;73:1720–1726.PubMedGoogle Scholar
  11. 11.
    Horowitz M, Gale RP, Sondel PM, et al. Graft-versus-leukemia reactions after bone marrow transplantation.Blood. 1990;75:555–562.PubMedCentralPubMedGoogle Scholar
  12. 12.
    Sinkovics JG, Shullenberger CC, Howe CD. Prolongation and prevention of Rauscher virus mouse leukemia by spleen cells of naturally resistant or actively immunized mice.Clin Res. 1965;13:36–39.Google Scholar
  13. 13.
    Boranic M, Tonkovic I. Time pattern of the antileukemia effect of graft-versus-host reaction in mice, I: cellular events.Cancer Res. 1971;31:1140–1147.PubMedGoogle Scholar
  14. 14.
    Bortin MM, Truitt RL, Rimm AA, Bach FH. Graft-versus- leukaemia reactivity induced by alloimmunization without augmentation of graft-versus-host reactivity.Nature. 1979;281:490–491.CrossRefPubMedGoogle Scholar
  15. 15.
    Slavin S, Weiss L, Morecki S, Weingensberg M. Eradication of murine leukemia with histoincompatible marrow grafts in mice conditioned with total lymphoid irradiation (TLI).Cancer Immunol Immunother. 1981;11:155–161.CrossRefGoogle Scholar
  16. 16.
    Truitt RL, Shih F-H, LeFever AV, Tempelis LD, Andreani M, Bortin MM. Characterization of alloimmunization-induced T lymphocytes reactivated against AKR leukemia in vitro and correlation with graft-vs-leukemia activity in vivo.J Immunol. 1983;131:2050–2058.PubMedGoogle Scholar
  17. 17.
    Meredith RF, O’Kunewick JP. Possibility of graft-vs-leukemia determinants independent of the major histocompatibility complex in allogeneic marrow transplantation.Transplantation. 1983;35:378–385.CrossRefPubMedGoogle Scholar
  18. 18.
    Weiss L, Weigensberg M, Morecki S, et al. Characterization of effector cells of graft vs leukemia (GVL) following allogeneic bone marrow transplantation in mice inoculated with murine B-cell leukemia (BCL1).Cancer Immunol Immunother. 1990;31:236–242.CrossRefPubMedGoogle Scholar
  19. 19.
    Truitt RL, Atasoylu AA. Impact of pretransplant conditioning and donor T cells on chimerism, graft-versus-host disease, graft-versus- leukemia reactivity, and tolerance after bone marrow transplantation.Blood. 1991;77:2515–2523.PubMedGoogle Scholar
  20. 20.
    Moscovitch M, Slavin S. Anti-tumor effects of allogeneic bone marrow transplantation in (NZB X NZW)F1 hybrids with spontaneous lymphosarcoma.J Immunol. 1984;132:997–1000.PubMedGoogle Scholar
  21. 21.
    Morecki S, Moshel Y, Gelfend Y, Pugatsch T, Slavin S. Induction of graft vs. tumor effect in a murine model of mammary adenocarcinoma.Int J Cancer. 1997;71:59–63.CrossRefPubMedGoogle Scholar
  22. 22.
    Morecki S, Yacovlev E, Diab A, Slavin S. Allogeneic cell therapy for a murine mammary carcinoma.Cancer Res. 1998;58:3891–3895.PubMedGoogle Scholar
  23. 23.
    Eibl B, Schwaighofer H, Nachbaur D, et al. 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.PubMedGoogle Scholar
  24. 24.
    Ueno NT, Rondón G, Mirza NQ, et al. Allogeneic peripheral-blood progenitor-cell transplantation for poor-risk patients with metastatic breast cancer.J Clin Oncol. 1998;16:986–993.CrossRefPubMedGoogle Scholar
  25. 25.
    Or R, Ackerstein A, Nagler A, et al. Allogeneic cell-mediated immunotherapy for breast cancer after autologous stem cell transplantation: a clinical pilot study.Cytokines Cell Mol Ther. 1998;4:1–6.PubMedGoogle Scholar
  26. 26.
    Higano CS, Brixey M, Bryant EM. Durable complete remission of acute nonlymphocytic leukemia associated with discontinuation of immunosuppression following relapse after allogeneic bone marrow transplantation: a case report of a probable graft-versus-leukemia effect.Transfusion. 1990;50:175–178.Google Scholar
  27. 27.
    Bacigalupo A, Van Lint MT, Occhini D, et al. Increased risk of leukemia relapse with high-dose cyclosporine A after allogeneic marrow transplantation for acute leukemia.Blood. 1991;77:1423–1428.PubMedGoogle Scholar
  28. 28.
    Weiss L, Reich S, Slavin S. Effect of cyclosporine A and methyl- prednisolone on the GVL effect across major histocompatibility barriers in mice following allogeneic bone marrow transplantation.Bone Marrow Transplant. 1990;6:229–233.PubMedGoogle Scholar
  29. 29.
    Kapelushnik J, Or R, Aker M, et al. Allogeneic cell therapy of severe beta thalassemia major by displacement of host stem cells in mixed chimera by donor blood lymphocytes.Bone Marrow Transplant. 1996;19:96–98.Google Scholar
  30. 30.
    Kapelushnik J, Aker M, Or R, et al. Allogeneic cell therapy as a new modality for displacement of genetically abnormal stem cells as part of the conditioning for allogeneic bone marrow transplantation. In: Ringden O, Hobbs VR, Stewart CG, eds.Correction of Genetic Diseases by Transplantation IV. Middlesex, UK: Cogent Press; 1997:111–119.Google Scholar
  31. 31.
    Aker M, Kapelushnik J, Pugatsch T, et al. Donor lymphocyte infusions to displace residual host hematopoietic cells after allogeneic BMT for beta thalassemia major.J Pediatr Hematol Oncol. 1998;20:145–148.CrossRefPubMedGoogle Scholar
  32. 32.
    Slavin S, Nagler A, Naparstek E, et al. Minitransplants and cell- based therapies for malignant and non-malignant disorders.Curr Opin Organ Transplant. 1999;4:184–188.CrossRefGoogle Scholar
  33. 33.
    Slavin S, Or R, Naparstek E, Ackerstein A, Weiss L. Cellular-mediated immunotherapy of leukemia in conjunction with autologous and allogeneic bone marrow transplantation in experimental animals and man [abstract].Blood. 1988;72(suppl 1):407a.Google Scholar
  34. 34.
    Slavin S, Naparstek E, Nagler A, Ackerstein A, Kapelushnik Y, Or R. Allogeneic cell therapy for relapsed leukemia following bone marrow transplantation with donor peripheral blood lymphocytes.Exp Hematol. 1995;23:1553–1562.PubMedCentralPubMedGoogle Scholar
  35. 35.
    Slavin S, Naparstek E, Nagler A, et al. Allogeneic cell therapy with donor peripheral blood cells and recombinant human interleukin-2 to treat leukemia relapse post allogeneic bone marrow transplantation.Blood. 1996;87:2195–2204.PubMedGoogle Scholar
  36. 36.
    Kolb HJ, Mittermuller J, Clemm C, et al. Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients.Blood. 1990;76:2462–2465.PubMedGoogle Scholar
  37. 37.
    Kolb HJ, Schattenberg A, Goldman JM, et al. Graft-versus- leukemia effect of donor lymphocyte transfusions in marrow grafted patients: European Group for Blood and Marrow Transplantation Working Party Chronic Leukemia.Blood. 1995;86:2041–2050.PubMedCentralPubMedGoogle Scholar
  38. 38.
    Collins RH, Shpilberg O, Drobyski WR, et al. Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation.J Clin Oncol. 1997;15:433–444.CrossRefPubMedCentralPubMedGoogle Scholar
  39. 39.
    Porter DL, Roth MS, McGarigle C, Ferrara JL, Antin JH. Induction of graft-versus-host disease as immunotherapy for relapsed chronic myeloid leukemia.N Engl J Med. 1994;330:100–106.CrossRefPubMedCentralPubMedGoogle Scholar
  40. 40.
    Mackinnon S, Papadopoulos EB, Carabassi MH, et al. Adoptive immunotherapy evaluating escalating doses of donor leukocytes for relapse of chronic myeloid leukemia after bone marrow transplantation: separation of graft-versus-leukemia responses from graft-versus-host disease.Blood. 1995;86:1261–1268.PubMedCentralPubMedGoogle Scholar
  41. 41.
    Gubbay I, Collignon J, Koopman P, et al. A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryologically expressed genes.Nature. 1990;346:245–250.CrossRefPubMedGoogle Scholar
  42. 42.
    Pugatsch T, Oppenheim A, Slavin S. Improved single-step PCR assay for sex identification post-allogeneic sex-mismatched BMT.Bone Marrow Transplant. 1996;17:273–275.PubMedGoogle Scholar
  43. 43.
    Kawasaki ES, Clark SS, Coyne MY, et al. Diagnosis of chronic myeloid and acute lymphocytic leukemias by detection of leukemia-specific mRNA sequences amplified in vitro.Proc Natl Acad Sci USA. 1988;85:5698–5702.CrossRefPubMedCentralPubMedGoogle Scholar
  44. 44.
    De Witte T, Schattenberg A, Preijers F, Mensink E. Treatment of relapse in recipients of lymphocyte depleted grafts with infusion of lymphocytes of the original bone marrow donor.Exp Hematol. 1992;20:723.Google Scholar
  45. 45.
    Bar BM, Schattenberg A, Mensink EJ, et al. Donor leukocyte infusions for chronic myeloid leukemia relapsed after allogeneic bone marrow transplantation.J Clin Oncol. 1993;11:513–519.CrossRefPubMedGoogle Scholar
  46. 46.
    Leber B, Walker IR, Rodrigues A, McBride JA, Carter R, Brian MC. Reinduction of remission of chronic myeloid leukemia by donor leukocyte transfusion following relapse after bone marrow transplantation: recovery complicated by initial pancytopenia and late dermatomyositis.Bone Marrow Transplant. 1993;12:405–407.PubMedGoogle Scholar
  47. 47.
    Papadopoulos EB, Ladanyi M, Emanuel D, et al. Infusions of donor leukocytes to treat Epstein-Barr virus-associated lympho- proliferative disorders after allogeneic bone marrow transplantation.N Engl J Med. 1994;330:1185–1191.CrossRefPubMedGoogle Scholar
  48. 48.
    Kuzushima K, Yamamoto M, Kimura H, et al. Establishment of anti-Epstein-Barr virus (EBV) cellular immunity by adoptive transfer of virus specific cytotoxic T lymphocytes from an HLA matched sibling to a patient with severe chronic active EBV infection.Clin Exp Immunol. 1996;103:192–198.CrossRefPubMedCentralPubMedGoogle Scholar
  49. 49.
    Stockschlaeder M, Storb R, Pepe M, et al. A pilot study of low-dose cyclosporin for graft-versus-host prophylaxis in marrow transplantation.Br J Haematol. 1992;80:49–54.CrossRefPubMedGoogle Scholar
  50. 50.
    Odom LF, August CS, Githens JH, et al. Remission of relapsed leukaemia during a graft-versus-host reaction: a “graft-versus- leukaemia reaction” in man?Lancet. 1978;2:537–538.CrossRefPubMedGoogle Scholar
  51. 51.
    Slavin S, Fuks Z, Kaplan HS, Strober S. Transplantation of allogeneic bone marrow without graft-versus-host disease using total lymphoid irradiation.J Exp Med. 1978;147:963–972.CrossRefPubMedGoogle Scholar
  52. 52.
    Weiss L, Reich S, Slavin S. Use of recombinant human interleukin- 2 in conjunction with bone marrow transplantation as a model for control of minimal residual disease in malignant hema- tological disorders, I: treatment of murine leukemia in conjunction with allogeneic bone marrow transplantation and IL-2-activated cell-mediated immunotherapy.Cancer Invest. 1992;10:19–26.CrossRefPubMedGoogle Scholar
  53. 53.
    Johnson BD, Drobyski WR, Truitt RL. Delayed infusion of normal donor cells after MHC-matched bone marrow transplantation provides an antileukemia reaction without graft-versus-host disease.Bone Marrow Transplant. 1993;11:329–336.PubMedGoogle Scholar
  54. 54.
    Naparstek E, Or R, Nagler A, et al. T-cell-depleted allogeneic bone marrow transplantation for acute leukaemia using Campath-1 antibodies and post-transplant administration of donor’s peripheral blood lymphocytes for prevention of relapse.Br J Haematol. 1995;89:506–515.CrossRefPubMedGoogle Scholar
  55. 55.
    Naparstek E, Nagler A, Or R, Slavin S. Allogeneic cell mediated immunotherapy using donor lymphocytes for prevention of relapse in patients treated with allogeneic BMT for hematological malignancies: North America. In: Cecka JM, Teraskaki PI, eds.Clinical Transplants, 1995. Los Angeles, Calif: UCLA Tissue Typing Laboratory; 1996:281–290.Google Scholar
  56. 56.
    vanRhee F, Lin F, Cullis JO, et al. Relapse of chronic myeloid leukemia after allogeneic bone marrow transplant: the case for giving donor leukocyte transfusions before the onset of hematologic relapse.Blood. 1994;83:3377–3383.PubMedGoogle Scholar
  57. 57.
    Sullivan KM, Storb R, Buckner CD, et al. Graft-versus-host disease as adoptive immunotherapy in patients with advanced hematologic neoplasms.N Engl J Med. 1989;320:828–834.CrossRefPubMedGoogle Scholar
  58. 58.
    Rosenberg SA. The immunotherapy and gene therapy of cancer.J Clin Oncol. 1992;10:180–192.CrossRefPubMedGoogle Scholar
  59. 59.
    Reisner Y, Kapoor N, Kirkpatrick D, et al. Transplantation for severe combined immunodeficiency with HLA-A,B,D,DR incompatible parental marrow cells fractionated by soybean agglutinin and sheep red blood cells.Blood. 1983;61:341–348.PubMedGoogle Scholar
  60. 60.
    Waldmann H, Polliack A, Hale G, et al. Elimination of graft-versus- host disease by in-vitro depletion of alloreactive lymphocytes with a monoclonal rat anti-human lymphocyte antibody (CAMPATH-1).Lancet. 1984;2:483–485.CrossRefPubMedGoogle Scholar
  61. 61.
    Reisner Y, Martelli MF. Bone marrow transplantation across HLA barriers by increasing the number of transplanted cells.Immunol Today. 1995;16:437–440.CrossRefPubMedGoogle Scholar
  62. 62.
    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.CrossRefPubMedCentralPubMedGoogle Scholar
  63. 63.
    Slavin S, Strober S. Spontaneous murine B-cell leukemia.Nature. 1978;272:624–626.CrossRefPubMedGoogle Scholar
  64. 64.
    Slavin S, Weiss L, Morecki S, et al. Ultrastructural, cell membrane and cytogenetic characteristics of B-cell leukemia (BCL1), a murine model of chronic lymphocytic leukemia.Cancer Res. 1981;41:4162–4166.PubMedGoogle Scholar
  65. 65.
    Raanani P, Dazzi F, Sohal J, et al. The rate and kinetics of molecular response to donor leucocyte transfusions in chronic myeloid leukaemia patients treated for relapse after allogeneic bone marrow transplantation.Br J Haematol. 1997;99:945–950.CrossRefPubMedGoogle Scholar
  66. 66.
    Hill GR, Crawford JM, Cooke KR, Brinson YS, Pan L, Ferrara JL. Total body irradiation and acute graft-versus-host disease: the role of gastrointestinal damage and inflammatory cytokines.Blood. 1997;90:3204–3213.PubMedGoogle Scholar
  67. 67.
    Cobold S, Martin G, Waldmann H. Monoclonal antibodies for the prevention of graft-versus-host disease and marrow graft rejection.Transplantation. 1986;42:239–247.CrossRefGoogle Scholar
  68. 68.
    Hale G, Xia MQ, Tighe HP, Dyer MJS, Waldmann H. The CAMPATH-1 antigen (CDw52).Tissue Antigens. 1990;35:118–127.CrossRefPubMedGoogle Scholar
  69. 69.
    Slavin S, Waldmann H, Or R, et al. Prevention of graft-versus-host disease in allogeneic bone marrow transplantation for leukemia by T cell depletion in vitro prior to transplantation.Transplant Proc. 1985;17:465–467.Google Scholar
  70. 70.
    Naparstek E, Or R, Nagler A, et al. Allogeneic BMT for leukemia using Campath-1 monoclonal antibodies and post transplant alloimmunization with donor lymphocytes [abstract].Exp Hematol. 1993;21:1061. Abstract 189.Google Scholar
  71. 71.
    Mackinnon S, Papadopoulos EB, Carabasi MH, et al. Adoptive immunotherapy evaluating escalating doses of donor leukocytes for relapse of chronic myeloid leukemia after bone marrow transplantation: separation of graft-versus-leukemia response from graft-versus-host disease.Blood. 1995;86:1261–1268.PubMedCentralPubMedGoogle Scholar
  72. 72.
    Bonini C, Ferrari G, Verzeletti S, et al. HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia.Science. 1997;276:1719–1724.CrossRefPubMedGoogle Scholar
  73. 73.
    Slavin S, Strober S, Fuks Z, Kaplan HS. Long-term survival of skin allografts in mice treated with fractionated total lymphoid irradiation.Science. 1976;193:1252–1254.CrossRefPubMedGoogle Scholar
  74. 74.
    Slavin S, Fuks Z, Kaplan HS, Strober S. Transplantation of allogeneic bone marrow without graft-versus-host disease using total lymphoid irradiation.J Exp Med. 1978;147:963–972.CrossRefPubMedGoogle Scholar
  75. 75.
    Slavin S. Total lymphoid irradiation (TLI).Immunol Today. 1987;8:88–92.CrossRefPubMedGoogle Scholar
  76. 76.
    Giralt S, Cohen A, Mehra R, et al. Preliminary results of fludarabine/ melphalan or 2CDA/melphalan as preparative regimens for allogeneic progenitor cell transplantation in poor candidates for conventional myeloablative conditioning [abstract].Blood. 1997;90(suppl 1):1853a.Google Scholar
  77. 77.
    Slavin S, Nagler A, Naparstek E, et al. Non-myeloablative 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.PubMedGoogle Scholar
  78. 78.
    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.CrossRefPubMedGoogle Scholar
  79. 79.
    Carella AM, Giralt S, Slavin S. Low intensity regimens with allogeneic hematopoietic stem cell transplantation as treatment of hematologic neoplasia.Haematologica. 2000;85:304–313.PubMedGoogle Scholar
  80. 80.
    Carella AM, Champlin R, Slavin S, McSweeney P, Storb R. Mini- allografts: ongoing trials in humans.Bone Marrow Transplant. 2000;25:345–350.CrossRefPubMedGoogle Scholar
  81. 81.
    Nagler A, Slavin S, Varadi G, Naparstek E, Samuel S, Or R. Allogeneic peripheral blood stem cell transplantation using a fludarabine- based low intensity conditioning regimen for malignant lymphoma.Bone Marrow Transplant. 2000;25:1021–1028.CrossRefPubMedGoogle Scholar
  82. 82.
    Nagler A, Ackerstein A, Kapelushnik J, Or R, Naparstek E, Slavin S. Donor lymphocyte infusion post-non-myeloablative allogeneic peripheral blood stem cell transplantation for chronic granulomatous disease.Bone Marrow Transplant. 1999;24:339–342.CrossRefPubMedGoogle Scholar
  83. 83.
    Kapelushnik J, Or R, Slavin S, Nagler A. Fludarabine based protocol for BMT in Fanconi anemia.Bone Marrow Transplant. 1997;29:1109–1110.CrossRefGoogle Scholar
  84. 84.
    Aker A, Varadi G, Slavin S, Nagler A. Fludarabine-based protocol for human umbilical cord blood transplantation in children with Fanconi’s anemia.J Pediatr Hematol Oncol. 1999;21:237–239.CrossRefPubMedGoogle Scholar
  85. 85.
    Kapelushnik J, Aker M, Pugatsch T, Samuel S, Slavin S. Bone marrow transplantation from a cadaveric donor.Bone Marrow Transplant. 1998;21:857–858.CrossRefPubMedGoogle Scholar
  86. 86.
    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.CrossRefPubMedCentralPubMedGoogle Scholar
  87. 87.
    Kottaridis PD, Milligan DW, Chopra R, et al. In vivo CAMPATH- 1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation.Blood. 2000;96:2419–2425.PubMedGoogle Scholar
  88. 88.
    Slavin S, Ackerstein A, Morecki S, Gelfand Y, Cividalli G. Immunotherapy of relapsed resistant chronic myelogenous leukemia post allogeneic bone marrow transplantation with alloantigens pulsed donor lymphocytes.Bone Marrow Transplant. 2001;28:795–798.CrossRefPubMedGoogle Scholar
  89. 89.
    Falkenburg JHF, Faber LM, van den Elshout M, et al. Generation of donor-derived antileukemic cytotoxic T-lymphocyte responses for treatment of relapsed leukemia after allogeneic HLA-identical bone marrow transplantation.J Immunother. 1993;14:305–309.CrossRefGoogle Scholar
  90. 90.
    Slavin S, Nagler A, Varadi G, Or R. Graft vs autoimmunity following allogeneic non-myeloablative blood stem cell transplantation in a patient with chronic myelogenous leukemia and severe systemic psoriasis and psoriatic polyarthritis.Exp Hematol. 2000;28:853–857.CrossRefPubMedGoogle Scholar
  91. 91.
    Childs RW, Clave E, Tisdale J, Plante M, Hensel N, Barrett J. 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.CrossRefPubMedGoogle Scholar
  92. 92.
    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.CrossRefPubMedCentralPubMedGoogle Scholar
  93. 93.
    Slavin S. Immunotherapy of cancer with alloreactive lymphocytes.Lancet Oncol. 2001;2:491–498.CrossRefPubMedGoogle Scholar
  94. 94.
    Giralt S, Estey E, Albitar M, et al. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia with myeloablative therapy.Blood. 1997;89:4531–4536.PubMedGoogle Scholar
  95. 95.
    Slavin S, Nagler A, Naparstek E, et al. Successful replacement of conventional bone marrow transplantation with high-dose chemoradiotherapy with well tolerated nonmyeloablative conditioning in preparation for the treatment of malignant and nonmalignant diseases [abstract].Blood. 1997;90:534a.Google Scholar

Copyright information

© The Japanese Society of Hematology 2003

Authors and Affiliations

  1. 1.Department of Bone Marrow Transplantation and Cancer Immunotherapy, Cell Therapy and Transplantation Research Center, The Danny Cunniff Leukemia Research LaboratoryHadassah University HospitalJerusalemIsrael

Personalised recommendations