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Cellular Therapy

Long-term results of adjuvant donor lymphocyte transfusion in AML after allogeneic stem cell transplantation

Bone Marrow Transplantation volume 51, pages 663–667 (2016)Cite this article

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Abstract

Adjuvant transfusion of donor lymphocytes (aDLT) may reduce the risk of relapse after allogeneic stem cell transplantation in high-risk AML. We performed a retrospective analysis on the safety and efficacy of aDLT in a cohort of 46 patients. To be eligible for aDLT, patients had to be in CR for at least 120 days from transplantation, off immunosuppression for ⩾30 days and free of GvHD. Thirty-four patients with similar disease characteristics and fulfilling the same selection criteria served as controls. Median follow-up among aDLT recipients was 7.2 years. Ten patients (22%) relapsed inspite of aDLT, as compared with 53% in the control group. Induction of GvHD was the main complication. However, non-relapse mortality was low with patients dying from infection (n=2), severe chronic GvHD (n=1) and secondary malignancy (n=2). At the time of analysis, 31/46 aDLT recipients were alive in CR at a median of 5.7 years after first aDLT. Overall survival at 7 years after transplant was 67% as compared with 31% in the control group (P<0.001). In conclusion, aDLT is safe, when given in escalating doses to a well predefined group of patients. Long-term survival can be achieved.

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References

  1. Mrózek K, Marcucci G, Nicolet D, Maharry KS, Becker H, Whitman SP et al. Prognostic significance of the European LeukemiaNet standardized system for reporting cytogenetic and molecular alterations in adults with acute myeloid leukemia. J Clin Oncol 2012; 30: 4515–4523.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Schmid C, Labopin M, Nagler A, Bornhäuser M, Finke J, Fassas A et al. Donor lymphocyte infusion in the treatment of first hematological relapse after allogeneic stem-cell transplantation in adults with acute myeloid leukemia: a retrospective risk factors analysis and comparison with other strategies by the EBMT Acute Leukemia Working Party. J Clin Oncol 2007; 25: 4938–4945.

    Article  CAS  PubMed  Google Scholar 

  3. Shaw BE, Russell NH . Treatment options for the management of acute leukaemia relapsing following an allogeneic transplant. Bone Marrow Transplant 2008; 41: 495–503.

    Article  CAS  PubMed  Google Scholar 

  4. Kolb HJ, Günther W, Schumm M, Holler E, Wilmanns W, Thierfelder S . Adoptive immunotherapy in canine chimeras. Transplantation 1997; 63: 430–436.

    Article  CAS  PubMed  Google Scholar 

  5. Faber LM, van Luxemburg-Heijs SA, Veenhof WF, Willemze R, Falkenburg JH . Generation of CD4+ cytotoxic T-lymphocyte clones from a patient with severe graft-versus-host disease after allogeneic bone marrow transplantation: implications for graft-versus-leukemia reactivity. Blood 1995; 86: 2821–2828.

    CAS  PubMed  Google Scholar 

  6. Kolb HJ, Mittermüller J, Clemm C, Holler E, Ledderose G, Brehm G 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. Collins RH Jr, Shpilberg O, Drobyski WR, Porter DL, Giralt S, Champlin R 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 

  8. Molldrem JJ, Lee PP, Wang C, Felio K, Kantarjian HM, Champlin RE et al. Evidence that specific T lymphocytes may participate in the elimination of chronic myelogenous leukemia. Nat Med 2000; 6: 1018–1023.

    Article  CAS  PubMed  Google Scholar 

  9. Schmid C, Schleuning M, Ledderose G, Tischer J, Kolb HJ . Sequential regimen of chemotherapy, reduced-intensity conditioning for allogeneic stem-cell transplantation, and prophylactic donor lymphocyte transfusion in high-risk acute myeloid leukemia and myelodysplastic syndrome. J Clin Oncol 2005; 23: 5675–5687.

    Article  PubMed  Google Scholar 

  10. Krishnamurthy P, Potter VT, Barber LD, Kulasekararaj AG, Lim ZY, Pearce RM et al. Outcome of donor lymphocyte infusion after T cell-depleted allogeneic hematopoietic stem cell transplantation for acute myelogenous leukemia and myelodysplastic syndromes. Biol Blood Marrow Transplant 2013; 19: 562–568.

    Article  PubMed  Google Scholar 

  11. Marks DI, Lush R, Cavenagh J, Milligan DW, Schey S, Parker A et al. The toxicity and efficacy of donor lymphocyte infusions given after reduced-intensity conditioning allogeneic stem cell transplantation. Blood 2002; 100: 3108–3114.

    Article  CAS  PubMed  Google Scholar 

  12. Roddie C, Peggs KS . Donor lymphocyte infusion following allogeneic hematopoietic stem cell transplantation. Expert Opin Biol Ther 2011; 11: 473–487.

    Article  PubMed  Google Scholar 

  13. Loren AW, Porter DL . Donor leukocyte infusions for the treatment of relapsed acute leukemia after allogeneic stem cell transplantation. Bone Marrow Transplant 2008; 41: 483–493.

    Article  CAS  PubMed  Google Scholar 

  14. De Lima M, Bonamino M, Vasconcelos Z, Colares M, Diamond H, Zalcberg I 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 2001; 27: 73–78.

    Article  CAS  PubMed  Google Scholar 

  15. Liga M, Triantafyllou E, Tiniakou M, Lambropoulou P, Karakantza M, Spyridonidis A et al. High alloreactivity of low-dose prophylactic donor lymphocyte infusion in patients with acute leukemia undergoing allogeneic hematopoietic cell transplantation with an alemtuzumab-containing conditioning regimen. Biol Blood Marrow Transplant 2013; 19: 75–81.

    Article  CAS  PubMed  Google Scholar 

  16. Mackinnon S, Papadopoulos EB, Carabasi MH, Reich L, Collins NH, Boulad F et al. Adoptive immunotherapy evaluating escalating doses of donor leukocytes for relapse of chronic myeloid leukemia after bone marrow transplantation: separation of graft-versus-leukemia responses from graft-versus-host disease. Blood 1995; 86: 1261–1268.

    CAS  PubMed  Google Scholar 

  17. Dazzi F, Szydlo RM, Craddock C, Cross NC, Kaeda J, Chase A et al. Comparison of single-dose and escalating-dose regimens of donor lymphocyte infusion for relapse after allografting for chronic myeloid leukemia. Blood 2000; 95: 67–71.

    CAS  PubMed  Google Scholar 

  18. Bethge WA, Hegenbart U, Stuart MJ, Storer BE, Maris MB, Flowers ME et al. Adoptive immunotherapy with donor lymphocyte infusions after allogeneic hematopoietic cell transplantation following nonmyeloablative conditioning. Blood 2004; 103: 790–795.

    Article  CAS  PubMed  Google Scholar 

  19. Dey BR, McAfee S, Colby C, Sackstein R, Saidman S, Tarbell N et al. Impact of prophylactic donor leukocyte infusions on mixed chimerism, graft-versus-host disease, and antitumor response in patients with advanced hematologic malignancies treated with nonmyeloablative conditioning and allogeneic bone marrow transplantation. Biol Blood Marrow Transplant 2003; 9: 320–329.

    Article  PubMed  Google Scholar 

  20. Massenkeil G, Nagy M, Lawang M, Rosen O, Genvresse I, Geserick G et al. Reduced intensity conditioning and prophylactic DLI can cure patients with high-risk acute leukaemias if complete donor chimerism can be achieved. Bone Marrow Transplant 2003; 31: 339–345.

    Article  CAS  PubMed  Google Scholar 

  21. Rettinger E, Willasch AM, Kreyenberg H, Borkhardt A, Holter W, Kremens B et al. Preemptive immunotherapy in childhood acute myeloid leukemia for patients showing evidence of mixed chimerism after allogeneic stem cell transplantation. Blood 2011; 118: 5681–5688.

    Article  CAS  PubMed  Google Scholar 

  22. Rosenow F, Berkemeier A, Krug U, Müller-Tidow C, Gerss J, Silling G et al. CD34(+) lineage specific donor cell chimerism for the diagnosis and treatment of impending relapse of AML or myelodysplastic syndrome after allo-SCT. Bone Marrow Transplant 2013; 48: 1070–1076.

    Article  CAS  PubMed  Google Scholar 

  23. Yan CH, Liu DH, Liu KY, Xu LP, Liu YR, Chen H et al. Risk stratification-directed donor lymphocyte infusion could reduce relapse of standard-risk acute leukemia patients after allogeneic hematopoietic stem cell transplantation. Blood 2012; 119: 3256–3262.

    Article  CAS  PubMed  Google Scholar 

  24. Schleuning M . Adoptive allogeneic immunotherapy–history and future perspectives. Transfus Sci 2000; 23: 133–150.

    Article  CAS  PubMed  Google Scholar 

  25. Stem Cell Trialists Collaborative Group. Allogeneic peripheral blood stem-cell compared with bone marrow transplantation in the management of hematologic malignancies: an individual patient data meta-analysis of nine randomized trials. J Clin Oncol 2005; 23: 5074–5087.

    Article  Google Scholar 

  26. Alyea EP, Kim HT, Ho V, Cutler C, DeAngelo DJ, Stone R et al. Impact of conditioning regimen intensity on outcome of allogeneic hematopoietic cell transplantation for advanced acute myelogenous leukemia and myelodysplastic syndrome. Biol Blood Marrow Transplant 2006; 12: 1047–1055.

    Article  PubMed  Google Scholar 

  27. Baron F, Labopin M, Niederwieser D, Vigouroux S, Cornelissen JJ, Malm C et al. Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplatation for acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European group for blood and marrow transplantation. Leukemia 2012; 26: 2462–2468.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank our data managers A Cook, C Rottmann (Wiesbaden), E Damann (Hannover) and M Rothmayer (Munich) for excellent assistance in data acquisition.

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Author notes

  1. Z Jedlickova and C Schmid: These authors contributed equally to this work.

Authors and Affiliations

  1. Center for Hematopoietic Cell Transplantation, Deutsche Klinik für Diagnostik Helios Klinik, Wiesbaden, Germany

    Z Jedlickova, H Baurmann, R Schwerdtfeger & M Schleuning

  2. Department of Medicine II, University Hospital, Frankfurt, Germany

    Z Jedlickova

  3. Department of Hematology and Oncology, Klinikum Augsburg, Germany

    C Schmid

  4. Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany

    C Koenecke

  5. Department of Medicine I, Clinical Center, Bremen Mitte, Germany

    B Hertenstein

  6. Department of Medicine III, Grosshadern, University Hospital of Munich (Ludwig Maximilians University), Munich, Germany

    J Tischer

  7. Department of Medicine III, University Hospital rechts der Isar, Munich, Germany

    H-J Kolb

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  1. Z Jedlickova
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Correspondence to M Schleuning.

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Jedlickova, Z., Schmid, C., Koenecke, C. et al. Long-term results of adjuvant donor lymphocyte transfusion in AML after allogeneic stem cell transplantation. Bone Marrow Transplant 51, 663–667 (2016). https://doi.org/10.1038/bmt.2015.234

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  • DOI: https://doi.org/10.1038/bmt.2015.234

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