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Donor Lymphocyte Infusions

Prophylactic donor lymphocyte infusions after moderately ablative chemotherapy and stem cell transplantation for hematological malignancies: high remission rate among poor prognosis patients at the expense of graft-versus-host disease

Bone Marrow Transplantation volume 27, pages 73–78 (2001)Cite this article

Abstract

We investigated the use of ‘prophylactic’ donor lymphocyte infusions (DLI) containing 1 × 107 CD3+ cells, given at 30, 60 and 90 days post-allogeneic blood and marrow transplantation (BMT), following conditioning with fludarabine 30 mg/m2/4 days and melphalan 70 mg/m2/2 days. GVHD prophylaxis consisted of cyclosporin A (CsA) 2 mg/kg daily with early tapering by day 60. Our goals were the rapid achievement of chimerism and disease control, providing an immunological platform for DLIs to treat refractory patients with hematological malignancies. Twelve heavily pre-treated patients with life expectancy less than 6 months were studied; none were in remission. Diagnoses were AML (n = 4), MDS (n = 1), ALL (n = 3), CML (n = 3) and multiple myeloma (n = 1). Response rate was 75%. Three patients are alive at a median of 450 days (range, 450–540). Two patients are in remission of CML in blast crisis and AML for more than 14 months. Median survival is 116 days (range, 25–648). Six patients received 12 DLIs; three patients developed acute GVHD after the first infusion and were excluded from further DLIs, but no GVHD occurred among patients receiving subsequent DLIs. One patient with CML in blast crisis went into CR after the first DLI. The overall incidence of acute GVHD was 70%. Primary causes of death were infections (n = 3), acute GVHD (n = 3), chronic GVHD (n = 1) and disease relapse (n = 2). We observed high response and chimerism rates at the expense of an excessive incidence of GVHD. DLI given at day +30 post BMT caused GVHD in 50% of the patients, and its role in this setting remains unclear. Bone Marrow Transplantation (2001) 27, 73–78.

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References

  1. Kolb H, 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 

  2. 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

    CAS  PubMed  Google Scholar 

  3. Giralt S, Khouri I, Braunschweig I et al. Melphalan and purine analog containing preparative regimens. Less intensive conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation Blood 1999 94: Abstr. 2518

    Google Scholar 

  4. Mackinnon S, Papadopoulos EB, Carabasi MH et al. Adoptive immunotherapy evaluating escalating doses of donor leukocytes for relapse of chronic myelogenous leukemia after bone marrow transplantation: separation of graft-versus-leukemia responses from graft-versus-host disease Blood 1995 85: 1261–1269

    Google Scholar 

  5. Bacigalupo A, van Lint MT, Occhini D et al. Increased risk of leukemia relapse with high-dose cyclosporine after allogeneic marrow transplantation for acute leukemia Blood 1991 77: 1423–1428

    CAS  PubMed  Google Scholar 

  6. Carlens S, Aschan J, Remberger M et al. Low dose cyclosporine of short duration increases the risk of mild and moderate graft-versus-host disease and reduces the risk of relapse in HLA-identical sibling marrow transplantation recipients with leukaemia Bone Marrow Transplant 1999 24: 629–635

    Article  CAS  PubMed  Google Scholar 

  7. Zubrod CG, Scheniderman M, Frei E et al. Appraisal of methods for the study of chemotherapy of cancer in man: comparative therapeutic trial of nitrogen mustard and trimethylene thioposphoramide J Chron Dis 1960 11: 7–33

    Article  Google Scholar 

  8. Bearman SI, Appelbaum FR, Buckner CD et al. Regimen related toxicities in patients undergoing bone marrow transplantation J Clin Oncol 1988 6: 1562–1566

    Article  CAS  PubMed  Google Scholar 

  9. Przepiorka D, Weisdorf D, Martin P et al. Consensus conference on acute GVHD grading Bone Marrow Transplant 1995 15: 825–828

    CAS  PubMed  Google Scholar 

  10. Shulman HM, Sullivan KM, Weiden PL et al. Chronic graft-versus-host disease syndrome in man. A long term clinical pathologic study of 20 Seattle patients Am J Med 1980 69: 204–208

    Article  CAS  PubMed  Google Scholar 

  11. Kaplan E, Meier P . Non parametric estimation from incomplete observations J Am Stat Assoc 1958 53: 457–462

    Article  Google Scholar 

  12. Elmaagacli AH, Beelen DW, Opalka B et al. The risk of residual molecular and cytogenetic disease in patients with Philadelphia-chromosome positive first chronic phase chronic myelogenous leukemia is reduced after transplantation of allogeneic peripheral blood stem cells compared with bone marrow Blood 1999 94: 384–389

    CAS  PubMed  Google Scholar 

  13. Przepiorka D, Ippolitti C, Khouri I et al. Allogeneic transplantation for advanced leukemia: improved short-term outcome with blood stem cell grafts and tacrolimus Blood 1996 62: 1806–1810

    CAS  Google Scholar 

  14. Spitzer TR, McAfee S, Sackstein R et al. Mixed lymphohematopoietic chimerism following non-myeloablative conditioning and HLA-matched allogeneic bone marrow transplantation: the effects of chimerism and anti-tumor response of prophylactic donor lymphocyte infusions Blood 1999 94: Abstr. 31340

  15. Sykes M, Sachs DH, Spitzer TR . Mixed chimerism followed by DLI for lymphohematopoietic GVH reactions without GVHD: from animal models to patients Hematology 1999 pp 405–412

  16. Pelot MR, Pearson DA, Swenson K et al. Lymphohematopoietic graft-versus-host reactions can be induced without graft-versus-host disease in murine mixed chimeras established with a cyclophosphamide-based non-myeloablative conditioning regimen Biol Blood Marrow Transplant 1999 5: 133–139.

    Article  CAS  PubMed  Google Scholar 

  17. Barrett AJ, Mavroudis D, Tisdale J et al. T cell-depleted bone marrow transplantation and delayed T cell add-back to control acute GVHD and conserve a graft-versus-leukemia effect Bone Marrow Transplant 1998 6: 543–551

    Article  Google Scholar 

  18. Falkenburg JHF, Wafelman AR, Joosten P et al. Complete remission of accelerated phase chronic myeloid leukemia by treatment with leukemia-reactive cytotoxic T lymphocytes Blood 1999 94: 1201–1208

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Bone Marrow Transplantation Unit, Instituto Nacional de Cancer, Rio de Janeiro, Brazil

    M de Lima, M Bonamino, Z Vasconcelos, M Colares, H Diamond, I Zalcberg, R Tavares, D Lerner, R Byington, L Bouzas, Jda Matta, C Andrade, L Carvalho, V Pires, B Barone, C Maciel & D Tabak

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  1. M de Lima
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de Lima, M., Bonamino, M., Vasconcelos, Z. et al. Prophylactic donor lymphocyte infusions after moderately ablative chemotherapy and stem cell transplantation for hematological malignancies: high remission rate among poor prognosis patients at the expense of graft-versus-host disease. Bone Marrow Transplant 27, 73–78 (2001). https://doi.org/10.1038/sj.bmt.1702726

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