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Lymphoma

Graft-versus-lymphoma effect of donor lymphocyte infusion in indolent lymphomas relapsed after allogeneic stem cell transplantation

Summary:

Donor lymphocyte infusions (DLI) are used to treat relapsed haematological diseases after allogeneic stem cell transplantation (SCT). We treated seven patients with DLI for indolent non-Hodgkin's lymphoma relapsed after SCT. In available blood and bone marrow samples, lymphoma cells were analysed by real-time quantitative polymerase chain reaction of t(14;18)-positive cells in follicular lymphoma, and by immunophenotyping in small lymphocytic lymphoma. Before DLI, three patients were treated with chemo- and/or radiotherapy, and one with rituximab. Evaluable responses to pre-DLI therapy were stable disease in one and partial remission (PR) in two patients. Six patients responded to DLI (complete remission (CR) in four and PR in two). After DLI, acute graft-versus-host disease (GVHD) occurred in 3/6 patients, classified as grade 2, whereas only limited chronic GVHD was seen (n=5). The four continuous CR are lasting for median 65+ (43–89) months. In the remaining patient, not responding to DLI, progressive disease was seen later on; chemotherapy followed by another DLI resulted in CR. In three cases, clinical responses to DLI could be substantiated by molecular or immunophenotypic analysis of lymphoma cells. We conclude that DLI is effective for treatment of indolent lymphoma relapsing after SCT.

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References

  1. Verdonck LF, Dekker AW, Lokhorst HM et al. Allogeneic versus autologous bone marrow transplantation for refractory and recurrent low-grade non-Hodgkin's lymphoma. Blood 1997; 90: 4201–4205.

    CAS  PubMed  Google Scholar 

  2. Van Besien K, Sobocinski KA, Rowlings PA et al. Allogeneic bone marrow transplantation for low grade lymphoma. Blood 1998; 92: 1832–1836.

    CAS  PubMed  Google Scholar 

  3. Mandigers CMPW, Raemaekers JMM, Schattenberg AVMB et al. Allogeneic bone marrow transplantation with T-cell depleted marrow grafts for patients with poor-risk relapsed low-grade non-Hodgkin's lymphoma. Br J Haematol 1998; 100: 198–206.

    Article  CAS  PubMed  Google Scholar 

  4. Gribben JG, Neuberg D, Barber M et al. Detection of residual lymphoma cells by polymerase chain reaction in peripheral blood is significantly less predictive for relapse than detection in bone marrow. Blood 1994; 83: 3800–3807.

    CAS  PubMed  Google Scholar 

  5. Bierman PJ, Vose JM, Anderson JR et al. High-dose therapy with autologous hematopoietic rescue for follicular low-grade non-Hodgkin's lymphoma. J Clin Oncol 1997; 15: 445–450.

    Article  CAS  PubMed  Google Scholar 

  6. Jones RJ, Ambinder RF, Piantadosi S, Santos GW . Evidence of a graft-versus-lymphoma effect associated with allogeneic bone marrow transplantation. Blood 1991; 77: 649–653.

    CAS  PubMed  Google Scholar 

  7. Van Besien KW, De Lima M, Giralt SA et al. Management of lymphoma recurrence after allogeneic transplantation: the relevance of graft-versus-lymphoma effect. Bone Marrow Transplant 1997; 19: 977–982.

    Article  CAS  PubMed  Google Scholar 

  8. Bär BMAM, Schattenberg A, Mensink EJBM et al. Donor leukocyte infusions for chronic myeloid leukemia relapsed after allogeneic bone marrow transplantation. J Clin Oncol 1993; 11: 513–519.

    Article  PubMed  Google Scholar 

  9. Kolb HJ, Schattenberg A, Goldman JM et al. for the European Group for Blood and Marrow Transplantation Working Party Chronic Leukemia. Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. Blood 1995; 86: 2041–2050.

    CAS  PubMed  Google Scholar 

  10. 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.

    Article  PubMed  Google Scholar 

  11. Verdonck LF, Lokhorst HM, Dekker AW et al. Graft-versus-myeloma effect in two cases. Lancet 1996; 347: 800–801.

    Article  CAS  PubMed  Google Scholar 

  12. Lokhorst HM, Schattenberg A, Cornelissen JJ et al. Donor leukocyte infusions are effective in relapsed multiple myeloma after allogeneic bone marrow transplantation. Blood 1997; 90: 4206–4211.

    CAS  PubMed  Google Scholar 

  13. 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.

    Article  CAS  PubMed  Google Scholar 

  14. Hunault-Berger M, Ifrah N, Solal-Celigny P . Intensive therapies in follicular non-Hodgkin's lymphomas. Blood 2002; 100: 1141–1152.

    CAS  PubMed  Google Scholar 

  15. Branson K, Chopra R, Kottaridis PD et al. Role of nonmyeloablative allogeneic stem-cell transplantation after failure of autologous transplantation in patients with lymphoproliferative malignancies. J Clin Oncol 2002; 20: 4022–4031.

    Article  PubMed  Google Scholar 

  16. Mandigers CMPW, Meijerink JPP, Raemaekers JMM et al. Graft-versus-lymphoma effect of donor leucocyte infusion shown by real-time quantitative PCR analysis of t(14;18). Lancet 1998; 352: 1522–1523.

    Article  CAS  PubMed  Google Scholar 

  17. De Witte T, Hoogenhout J, de Pauw B et al. Depletion of donor lymphocytes by counterflow centrifugation successfully prevents acute graft-versus-host disease in matched allogeneic marrow transplantation. Blood 1986; 67: 1302–1308.

    CAS  PubMed  Google Scholar 

  18. Verdonck LF, de Gast GC, van Heugten HG et al. A fixed low number of T cells in HLA-identical allogeneic bone marrow transplantation. Blood 1990; 75: 776–780.

    CAS  PubMed  Google Scholar 

  19. Glucksberg H, Storb R, Fefer A et al. 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 

  20. Shulman HM, Sullivan KM, Weiden PL et al. Chronic graft-versus-host syndrome in man; a long-term clinicopathologic study of 20 Seattle patients. Am J Med 1980; 69: 204–217.

    Article  CAS  PubMed  Google Scholar 

  21. Meijerink J, Mandigers C, Van de Locht L et al. A novel method to compensate for different amplification efficiencies between patient DNA samples in quantitative real-time PCR. J Mol Diagn (Part B of Am J Pathol) 2001; 3: 55–61.

    CAS  Google Scholar 

  22. Mandigers CMPW, Meijerink JPP, Mensink EJBM et al. Lack of correlation between numbers of circulating t(14;18) positive cells and response to first-line treatment in follicular lymphoma. Blood 2001; 98: 940–944.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We kindly thank Evelyn Tönnissen (Central Hematology Laboratory, University Medical Center Nijmegen, The Netherlands) for technical assistance.

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Correspondence to C M P W Mandigers.

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Mandigers, C., Verdonck, L., Meijerink, J. et al. Graft-versus-lymphoma effect of donor lymphocyte infusion in indolent lymphomas relapsed after allogeneic stem cell transplantation. Bone Marrow Transplant 32, 1159–1163 (2003). https://doi.org/10.1038/sj.bmt.1704290

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