Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Case Report
  • Published:

Immunotherapy of relapsed resistant chronic myelogenous leukemia post allogeneic bone marrow transplantation with alloantigen pulsed donor lymphocytes

Bone Marrow Transplantation volume 28, pages 795–798 (2001)Cite this article

Abstract

Allogeneic cell-mediated immunotherapy with donor lymphocyte infusion (DLI) can successfully reverse chemoradiotherapy-resistant relapse in patients with chronic myeloid leukemia treated by allogeneic bone marrow transplantation (BMT). We describe the first successful attempt in 1992 to treat DLI-resistant relapse in a patient with CML in full hematologic relapse, using immunized donor lymphocytes. Donor lymphocytes were pulsed in vitro with a mixture of irradiated peripheral blood lymphocytes (PBL) obtained from both parents, in order to trigger alloactivation of donor lymphocytes against host alloantigens presented by parental cells, using as stimulating cells maternal PBL expressing the shared maternal haplotype and paternal PBL expressing the shared paternal haplotype of the patient. Full hematologic, cytogenetic and molecular remission was induced for the first time, independently of GVH, and has persisted for more than 9 years. To the best of our knowledge, this report represents the first successful immunotherapy with donor lymphocytes activated against host-type antigens. We suggest that immune donor PBL may be superior to DLI, possibly effective even when all other modalities fail, perhaps even independently of GVHD. Bone Marrow Transplantation (2001) 28, 795–798.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Slavin S, Or R, Naparstek W et al. Cellular-mediated immunotherapy of leukemia in conjunction with autologous and allogeneic bone marrow transplantation in experimental animals and man Blood 1988 72 (Suppl. 1): 407a (Abstr.)

    Google Scholar 

  2. Slavin S, Naparstek E, Nagler A et al. Allogeneic cell therapy for relapsed leukemia following bone marrow transplantation with donor peripheral blood lymphocytes Exp Hematol 1995 23: 1553–1562

    CAS  PubMed  Google Scholar 

  3. 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

    CAS  PubMed  Google Scholar 

  4. Kolb HJ, Schattenberg A, Goldman JM et al. Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients Blood 1995 86: 2041–2050

    CAS  PubMed  Google Scholar 

  5. Avichezer D, Gilboa-Garber N, Mumcuoglu M, Slavin S . Adoptive transfer of resistance to Pseudomonas aeruginosa infection by splenocytes and bone marrow cells from BALB/c mice immunized by Pseudomonas aeruginosa lectin preparations Infection 1989 17: 407–410

    Article  CAS  Google Scholar 

  6. Mumcuoglu M, Zakay-Rones Z, Weiss L, Slavin S . The effect of total or partial T-lymphocyte depletion on susceptibility to influenza virus infection and development of antiviral immunity in lethally irradiated mice reconstituted with immune syngeneic bone marrow grafts Bone Marrow Transplant 1991 7: 217–220

    CAS  PubMed  Google Scholar 

  7. Ilan Y, Nagler A, Adler R et al. Ablation of persistent hepatitis B virus infection by allogeneic bone marrow transplantation from an HBV immune donor: a preliminary report Gastroenterology 1993 104: 1818–1821

    Article  CAS  Google Scholar 

  8. Morecki S, Slavin S . Towards amplification of graft vs leukemia (GVL) effect while minimizing graft vs host disease (GVHD) J Hematother Stem Cell Res 2000 9: 355–377

    Article  CAS  Google Scholar 

  9. Ji YH, Weiss L, Zeira M et al. Increasing anti-leukemia effects while minimizing graft vs host responses following donor immunization prior to allogeneic cell therapy for murine B cell leukemia (submitted)

  10. Slavin S, Fuks Z, Kaplan HS, Strober S . Transplantation of allogeneic bone marrow without graft vs host disease using total lymphoid irradiation J Exp Med 1978 147: 963–972

    Article  CAS  Google Scholar 

  11. Weiss L, Slavin S . Prevention and treatment of graft-versus-host disease by down-regulation of anti-host reactivity with veto cells of host origin Bone Marrow Transplant 1999 23: 1139–1143

    Article  CAS  Google Scholar 

  12. Kwak LW, Taub DD, Duffey PL et al. Transfer of myeloma idiotype-specific immunity from an actively immunized marrow donor Lancet 1995 345: 1016–1022

    Article  CAS  Google Scholar 

  13. 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

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported in part by research grants from The Gabrielle Rich Leukemia Foundation, Baxter Healthcare Corporation, The Szydlowsky Foundation, The Himmelfarb Foundation. The work was performed in The Danny Cunniff Leukemia Research Laboratory. We also wish to thank Ryna and Melvin Cohen for their continuous support of our research program.

Author information

Authors and Affiliations

  1. Departments of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah University Hospital, Jerusalem, Israel

    S Slavin, A Ackerstein, S Morecki & Y Gelfand

  2. Department of Pediatrics, Hadassah University Hospital, Jerusalem, Israel

    G Cividalli

Authors
  1. S Slavin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A Ackerstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S Morecki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Y Gelfand
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G Cividalli
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Slavin, S., Ackerstein, A., Morecki, S. et al. Immunotherapy of relapsed resistant chronic myelogenous leukemia post allogeneic bone marrow transplantation with alloantigen pulsed donor lymphocytes. Bone Marrow Transplant 28, 795–798 (2001). https://doi.org/10.1038/sj.bmt.1703223

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1703223

Keywords

This article is cited by

Search

Advanced search

Quick links