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Relapse of Leukemia

A pilot study of cytoreductive chemotherapy combined with infusion of additional peripheral blood stem cells reserved at time of harvest for transplantation in case of relapsed hematologic malignancies after allogeneic peripheral blood stem cell transplant

Summary:

Reharvesting leukocytes from donors for a donor leukocyte infusion (DLI) is inconvenient and occasionally impossible in case of unrelated donors. It is well known that the effect of a growth factor-primed DLI is comparable to that of a nonprimed DLI. In total, 42 patients with hematologic malignancies and a high risk of relapse were allocated, on an intent-to-treat basis, a peripheral blood stem cell transplantation (PBSCT) from HLA-matched sibling donors, and then at the time of harvest, additional peripheral blood stem cells (PBSCs) were also reserved for a therapeutic primed DLI in case of relapse. In all, 12 patients who relapsed after allogeneic PBSCT were treated with mainly cytarabine-based chemotherapy followed by a cryopreserved PBSC infusion. The median dose of CD3+ and CD34+ cells for the primed DLIs was 1.43 × 108/kg and 4.75 × 106/kg, respectively. Six of the 12 relapsed patients exhibited a complete response after the primed DLI, plus their 1-year survival rate was 33%. The new development or progression of graft-versus-host disease after a primed DLI was observed in 50% of the patients. Overall, the survival at 1 year was 16.7%. Accordingly, the induction of a graft-versus-leukemia effect through a primed DLI, using additional PBSCs reserved at the original time of harvest, would appear to be feasible for patients with relapsed hematologic malignancies. Furthermore, this approach is also more convenient for donors.

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References

  1. Szer J, Grigg AP, Phillips GL, Sheridan WP . Donor leucocyte infusions after chemotherapy for patients relapsing with acute leukaemia following allogeneic BMT. Bone Marrow Transplant 1993; 11: 109–111.

    CAS  PubMed  Google Scholar 

  2. Sica S, Di Mario A, Salutari P et al. Chemotherapy and recombinant human granulocyte colony-stimulating factor primed donor leukocyte infusion for treatment of relapse after allogeneic bone marrow transplantation. Bone Marrow Transplant 1995; 16: 483–485.

    CAS  PubMed  Google Scholar 

  3. Alessandrino EP, Bernasconi P, Caldera D et al. Chemotherapy and donor peripheral blood progenitor cells for acute leukemia in early relapse after allogeneic bone marrow transplantation. Bone Marrow Transplant 1999; 23: 607–612.

    Article  CAS  PubMed  Google Scholar 

  4. Levine JE, Braun T, Penza SL et al. Prospective trial of chemotherapy and donor leukocyte infusions for relapse of advanced myeloid malignancies after allogeneic stem-cell transplantation. J Clin Oncol 2002; 20: 405–412.

    Article  CAS  PubMed  Google Scholar 

  5. Slovak ML, Kopecky KJ, Cassileth PA et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group study. Blood 2000; 96: 4075–4083.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  7. Sullivan KM . Acute and chronic graft-versus-host disease in man. Int J Cell Cloning 1986; 4: 42–93.

    Article  PubMed  Google Scholar 

  8. Sohn SK, Kim JG, Seo KW et al. GM-CSF-based mobilization effect in normal healthy donors for allogeneic peripheral blood stem cell transplantation. Bone Marrow Transplant 2002; 30: 81–86.

    Article  CAS  PubMed  Google Scholar 

  9. Giralt SA, Champlin RE . Leukemia relapse after allogeneic bone marrow transplantation: a review. Blood 1994; 84: 3603–3612.

    CAS  PubMed  Google Scholar 

  10. Horowitz M, Gale R, Sondel M et al. Graft-versus-leukemia reaction after bone marrow transplantation. Blood 1990; 75: 555–562.

    CAS  PubMed  Google Scholar 

  11. Marmont A, Horowitz M, Gale R et al. T-cell depletion of HLA-identical transplants in leukemia. Blood 1991; 78: 2120–2130.

    CAS  PubMed  Google Scholar 

  12. Sullivan K, Weiden P, 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: 1720–1728.

    CAS  PubMed  Google Scholar 

  13. Barrett AJ, Locatelli F, Treleaven JG et al. Second transplants for leukaemic relapse after bone marrow transplantation: high early mortality but favourable effect of chronic GVHD on continued remission. Br J Haematol 1991; 79: 567–574.

    Article  CAS  PubMed  Google Scholar 

  14. Kishi K, Takahashi S, Gondo H et al. Second allogeneic bone marrow transplantation for post-transplant leukemia relapse: results of survey of 66 cases in 24 Japanese institutes. Bone Marrow Transplant 1997; 19: 461–466.

    Article  CAS  PubMed  Google Scholar 

  15. Kolb HJ, Schattenberg A, Goldman JM et al. Graft-versus-leukemia effect of donor lymphocyte transfusion in marrow grafted patients. Blood 1995; 86: 2041–2059.

    CAS  PubMed  Google Scholar 

  16. Collins RH, Shpilberg O, Drobyski WR et al. Donor leukocyte infusion in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J Clin Oncol 1997; 15: 433–444.

    Article  PubMed  Google Scholar 

  17. Kumar L . Donor leukocyte infusion for relapse in chronic myelogenous leukemia. Lancet 1994; 344: 1101–1104.

    Article  CAS  PubMed  Google Scholar 

  18. Blaise D, Kuentz M, Fortanier C et al. Randomized trial of bone marrow versus lenograstim-primed blood cell allogeneic transplantation in patients with early-stage leukemia: a report from the Societe Francaise de Greffe de Moelle. J Clin Oncol 2000; 18: 537–546.

    Article  CAS  PubMed  Google Scholar 

  19. Powles R, Mehta J, Kulkarni S et al. Allogeneic blood and bone-marrow stem-cell transplantation in haematological malignant diseases: a randomized trial. Lancet 2000; 355: 1231–1237.

    Article  CAS  PubMed  Google Scholar 

  20. Russell JA, Larratt L, Brown C et al. Allogeneic blood stem cell and bone marrow transplantation for acute myelogenous leukemia and myelodysplasia: influence of stem cell source on outcome. Bone Marrow Transplant 1999; 24: 1177–1183.

    Article  CAS  PubMed  Google Scholar 

  21. Grigg A, Kannan K, Schwarer AP et al. Chemotherapy and granulocyte colony stimulating factor-mobilized blood cell infusion followed by interferon-α for relapsed malignancy after allogeneic bone marrow transplantation. Intern Med J 2001; 31: 15–22.

    Article  CAS  PubMed  Google Scholar 

  22. Lee JH, Lee KH, Kim S et al. Combination chemotherapy of intermediate-dose cytarabine, idarubicin, plus etoposide and subsequent mobilized donor leukocyte infusion for relapsed acute leukemia after allogeneic bone marrow transplantation. Leuk Res 2001; 25: 305–312.

    Article  CAS  PubMed  Google Scholar 

  23. Arpinati M, Green CL, Heimfeld S et al. Granulocyte-colony stimulating factor mobilizes T helper 2-inducing dendritic cells. Blood 2000; 95: 2484–2490.

    CAS  PubMed  Google Scholar 

  24. Pan L, Teshima T, Hill GR et al. Granulocyte colony-stimulating factor-mobilized allogeneic stem cell transplantation maintains graft-versus-leukemia effects through a perforin-dependent pathway while preventing graft-versus-host disease. Blood 1999; 93: 4071–4078.

    CAS  PubMed  Google Scholar 

  25. Reddy V, Hill GR, Pan L et al. G-CSF modulates cytokine profile of dendritic cells and decreases acute graft-versus-host disease through effects on the donor rather than the recipient. Transplantation 2000; 69: 691–693.

    Article  CAS  PubMed  Google Scholar 

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We gratefully acknowledge the support of our nursing staff.

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Correspondence to S K Sohn.

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Kim, J., Sohn, S., Kim, D. et al. A pilot study of cytoreductive chemotherapy combined with infusion of additional peripheral blood stem cells reserved at time of harvest for transplantation in case of relapsed hematologic malignancies after allogeneic peripheral blood stem cell transplant. Bone Marrow Transplant 33, 231–236 (2004). https://doi.org/10.1038/sj.bmt.1704328

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