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Donor Lymphocyte Infusions

Donor leukocyte infusions in acute lymphocytic leukemia

Bone Marrow Transplantation volume 26, pages 511–516 (2000)Cite this article

Abstract

Donor leukocyte infusion (DLI) has well-documented activity in CML but the role of DLI in other diseases is less well defined. To evaluate the strategy in acute lymphocytic leukemia (ALL) we evaluated 44 ALL patients from 27 centers who were treated with DLI. Patients with persistent or recurrent disease received DLI from the original marrow donor (30 matched related, four mismatched family, and 10 matched unrelated). Chemotherapy was given before DLI to 28 patients. Of 15 patients who received no pre-DLI chemotherapy, two achieved complete remissions, lasting 1112 and 764+ days. In four patients who received DLI as consolidation of remission induced by chemotherapy or immunosuppression-withdrawal, duration of remission post DLI was 65, 99, 195 and 672+ days. Of 25 patients who received DLI in the nadir after chemotherapy, 13 survived ⩾30 days post DLI but did not achieve remission, seven died within less than 30 days post DLI, and five entered remissions that lasted 42, 68, 83, 90, 193 days. Seven patients who did not respond to the initial DLI received a second DLI; none of these patients attained durable remission. Eighteen of 37 evaluable patients developed acute GVHD and five of 20 evaluable patients developed chronic GVHD. Overall actuarial survival is 13% at 3 years. In conclusion, DLI has limited benefit in ALL. New approaches are needed in this group of patients. Bone Marrow Transplantation (2000) 26, 511–516.

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References

  1. Barnes D, Loutit L, Neal F . Treatment of murine leukemia with X-rays and homologous bone marrow BMJ 1956 2: 626–630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Truitt RL, Johnson BD . Principles of graft-versus-leukemia reactivity Biol Blood Marrow Transplant 1995 1: 61–68

    CAS  PubMed  Google Scholar 

  3. Weiden PL, Sullivan KM, Flournoy N et al. Antileukemic effect of chronic graft-versus-host disease: contribution to improved survival after allogeneic marrow transplantation New Engl J Med 1981 304: 1529–1533

    Article  CAS  PubMed  Google Scholar 

  4. Gale RP, Champlin RE . How does bone-marrow transplantation cure leukaemia? Lancet 1984 2: 28–30

    Article  CAS  PubMed  Google Scholar 

  5. Horowitz MM, Gale RP, Sondel PM et al. Graft-versus-leukemia reactions after bone marrow transplantation Blood 1990 75: 555–562

    CAS  PubMed  Google Scholar 

  6. 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

    CAS  PubMed  Google Scholar 

  7. Bar B, Schattenberg A, Mesnick E . Donor leukocyte infusions for chronic myeloid leukemia after allogeneic bone marrow transplantation J Clin Oncol 1993 11: 513–519

    Article  CAS  PubMed  Google Scholar 

  8. Drobyski WR, Keever CA, Roth MS et al. Salvage immunotherapy using donor leukocyte infusions as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation: efficacy and toxicity of a defined T-cell dose Blood 1993 82: 2310–2318

    CAS  PubMed  Google Scholar 

  9. Porter DL, Roth MS, McGarigle C . Induction of graft-versus-host disease as immunotherapy for relapsed chronic myeloid leukemia New Engl J Med 1994 330: 100–106

    Article  CAS  PubMed  Google Scholar 

  10. Van Rhee 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

    CAS  PubMed  Google Scholar 

  11. 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

    CAS  PubMed  Google Scholar 

  12. 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 after allogeneic bone marrow transplantation Blood 1996 87: 2195–2204

    CAS  PubMed  Google Scholar 

  13. Collins RH Jr, 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

    Article  PubMed  Google Scholar 

  14. Mehta J . The first clinical use of donor leukocyte infusions for the treatment of leukemia relapsing after allogeneic bone marrow transplantation Blood 1996 87: 4010–4023

    CAS  PubMed  Google Scholar 

  15. Ferster A, Bujan W, Mouraux T et al. Complete remission following donor leukocyte infusion in ALL relapsing after haploidentical bone marrow transplantation Bone Marrow Transplant 1994 14: 331–332

    CAS  PubMed  Google Scholar 

  16. D'Hondt L, Chatelain C, Doyen C et al. Transient complete remission of acute lymphoblastic leukemia in relapse after allogeneic bone marrow transplantation induced by donor leukocyte transfusions Hematol Cell Ther 1996 38: 353–354

    Article  CAS  PubMed  Google Scholar 

  17. Kawakami T, Umehara S, Fukunaga M et al. Grade IV graft-versus-host disease and a 1-year remission following donor leukocyte transfusion for treatment of relapsed acute lymphoblastic leukemia (letter) Bone Marrow Transplant 1996 17: 464–465

    CAS  PubMed  Google Scholar 

  18. Russell L, Jacobsen N, Heilmann C et al. Treatment of relapse after allogeneic BMT with donor leukocyte infusions in 16 patients Bone Marrow Transplant 1996 18: 411–414

    CAS  PubMed  Google Scholar 

  19. Saw M, Teh A, Wong H, Bosco J . Haematological remission induced by donor leukocyte infusion in a case of Philadelphia positive acute lymphoblastic leukaemia relapsing after allogeneic bone marrow transplantation Int J Hematol 1997 65: 173–178

    Article  CAS  PubMed  Google Scholar 

  20. Yazaki M, Andoh M, Ito T et al. Successful prevention of hematological relapse for a patient with Philadelphia chromosome-positive acute lymphoblastic leukemia after allogeneic bone marrow transplantation by donor leukocyte infusion Bone Marrow Transplant 1997 19: 393–394

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  22. Atra A, Millar B, Shepherd V et al. Donor lymphocyte infusion for childhood acute lymphoblastic leukaemia relapsing after bone marrow transplantation Br J Haematol 1997 97: 165–168

    Article  CAS  PubMed  Google Scholar 

  23. Locatelli F, Comoli P, Giorgiani G et al. Infusion of donor-derived peripheral blood leukocytes after transplantation of cord blood progenitor cells can increase the graft-versus-leukaemia effect Leukemia 1997 11: 729–731

    Article  CAS  PubMed  Google Scholar 

  24. Lawson S, Darbyshire P . Use of donor lymphocytes in extramedullary relapse of childhood acute lymphoblastic leukaemia following bone marrow transplantation Bone Marrow Transplant 1998 22: 829–830

    Article  CAS  PubMed  Google Scholar 

  25. Berthou C, Leglise M, Herra A et al. Extramedullary relapse after favorable molecular response to donor leukocyte infusions for recurring acute leukemia Leukemia 1998 12: 1676–1681

    Article  CAS  PubMed  Google Scholar 

  26. Chang C, Lin S, Liu T et al. Donor leukocyte infusion as salvage therapy in an adult with relapsed acute lymphoblastic leukemia after allogeneic bone marrow transplantation J Formos Med Assoc 1998 97: 55–58

    CAS  PubMed  Google Scholar 

  27. Glucksberg H, Storb R, Fefer A . Clinical manifestations of graft-versus-host disease in human recipients of marrow from HLA-matched sibling donors Transplantation 1974 18: 295–304

    Article  CAS  PubMed  Google Scholar 

  28. Shulman HM, Sullivan KM, Weiden PL . Chronic graft-vs.-host syndrome in man. A long-term clinicopathological study of 20 Seattle patients Am J Med 1980 69: 204–217

    Article  CAS  PubMed  Google Scholar 

  29. Kaplan E, Meier P . Non-parametric estimation from incomplete observations J Am Stat Assoc 1958 53: 457–481

    Article  Google Scholar 

  30. Borgan, Liest'l K . A note on confidence intervals and bands for the survival curve based on transformations Scand J Stat 1990 17: 35–41

    Google Scholar 

  31. Kolb H-J . Adoptive immunotherapy in chimeras for the treatment of leukemia. In: Perry MC (ed) American Society of Clinical Oncology Educational Book American Society of Clinical Oncology: Alexandria, VA 1999 pp.235–240

    Google Scholar 

  32. Guinan EC, Gribben JG, Boussiotis VA et al. Pivotal role of the B7:CD28 pathway in transplantation tolerance and tumor immunity Blood 1994 84: 3261–3282

    CAS  PubMed  Google Scholar 

  33. Hirano N, Takahashi T, Takahashi T et al. Expression of costimulatory molecules in human leukemias Leukemia 1996 10: 1168–1176

    CAS  PubMed  Google Scholar 

  34. Freedman AS . Expression and function of adhesion receptors on normal B cells and B cell non-Hodgkin's lymphomas Semin Hematol 1993 30: 318–328

    CAS  PubMed  Google Scholar 

  35. Garrido F, Cabrera T, Concha A et al. Natural history of HLA expression during tumor development Immunol Today 1993 14: 491–499

    Article  CAS  PubMed  Google Scholar 

  36. Cardoso A, Schultze J, Boussiotis V et al. Pre-B acutelymphoblastic leukemia cells may induce T-cell anergy to alloantigen Blood 1996 88: 41–48

    CAS  PubMed  Google Scholar 

  37. Riddell S, Greenberg P . Adoptive immunotherapy withantigen-specific T cells. In: Thomas E, Blume K, Forman S (eds) Hematopoietic Cell Transplantation, 2nd edn Blackwell Science: Malden, MA 1999 pp.327–341

    Google Scholar 

Download references

Acknowledgements

We thank Shanna Morris for data management, John Klein for statistical analysis, Jane Pryor for assistance in manuscript preparation and the Leukemia Association of North Central Texas for financial support.

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Authors and Affiliations

  1. University of Texas Southwestern Medical Center, Dallas, TX, USA

    RH Collins Jr

  2. Baylor Sammons Cancer Center, Dallas, TX, USA

    RH Collins Jr, M Johnson & A Kirk

  3. H Lee Moffitt Cancer Center, Tampa, FL, USA

    S Goldstein

  4. University of Texas MD Anderson Cancer Center, Houston, TX, USA

    S Giralt

  5. University of Michigan, Ann Arbor, MI, USA

    J Levine

  6. University of Pennsylvania School of Medicine, PA, USA

    D Porter

  7. Medical College of Wisconsin, Milwaukee, WI, USA

    W Drobyski & M Horowitz

  8. National Heart Lung and Blood Institute, Bethesda, MD, USA

    J Barrett

  9. International Bone Marrow Transplant Registry, Milwaukee, WI, USA

    M Horowitz

  10. City of Hope, Duarte, CA, USA

    P Parker

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  1. RH Collins Jr
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Collins Jr, R., Goldstein, S., Giralt, S. et al. Donor leukocyte infusions in acute lymphocytic leukemia. Bone Marrow Transplant 26, 511–516 (2000). https://doi.org/10.1038/sj.bmt.1702555

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