Journal of Clinical Immunology

, Volume 28, Issue 4, pp 390–397 | Cite as

Modified Donor Lymphocyte Infusion (DLI) for the Prophylaxis of Leukemia Relapse after Hematopoietic Stem Cell Transplantation in Patients with Advanced Leukemia—Feasibility and Safety Study

  • Xiao-Jun Huang
  • Yu Wang
  • Dai-Hong Liu
  • Lan-Ping Xu
  • Huan Chen
  • Yu-Hong Chen
  • Wei Han
  • Hong-Xia Shi
  • Kai-Yan Liu



We retrospectively evaluated the feasibility and safety of a modified prophylactic donor lymphocytes infusion (DLI) approach in advanced leukemia.

Materials and methods

Thirty-three patients with advanced leukemia received modified prophylactic DLI; that is, granulocyte colony-stimulating factor-primed peripheral blood progenitor cells instead of steady-donor lymphocyte harvests were used, and a short-term immunosuppressive agent (cyclosporine A or methotrexate 10 mg once per week for 2 to 4 weeks) was used for prevention of DLI-associated graft versus host disease (GVHD) after human leukocyte antigen-identical sibling hematopoietic stem cell transplantation.


Thirty-nine infusions were performed in 33 patients. The mononuclear cells and median CD3+ cells infused for DLI were 1–2 × 108 and 0.93 × 106 per kilogram, respectively. Six patients experienced II–IV-grade acute GVHD. Twenty patients developed chronic GVHD. No GVHD-related death or transfusion-related pancytopenia was observed. With an 18-month median follow-up, 16 patients were in disease-free survival, and overall survival at 1 and 1.5 years was 69.0% and 50.2%, respectively.


The modified prophylactic DLI strategy might represent a step forward in the treatment of advanced leukemia.


Advanced leukemia donor lymphocytes infusion granulocyte colony-stimulating factor hematopoietic stem cell transplantation 



This article is supported in part from Hi-tech Research and Development Program of China, Innovation Team Program of Ministry of Education of China, National Outstanding Young Talent Natural Science Foundation, Leading Program of Clinical Faculty accredited by the Ministry of Health of China.


  1. 1.
    Huang XJ, Guo NL, Ren HY. An improved anti-leukemic effect achieved with donor progenitor cell infusion for relapse patients after allogeneic bone marrow transplantation. Chin Med J. 2003;116:736–41.PubMedGoogle Scholar
  2. 2.
    Huang XJ, Liu DH, Xu LP. Prophylactic infusion of donor granulocyte colony stimulating factor mobilized peripheral blood progenitor cells after allogeneic hematological stem cell transplantation in patients with high-risk leukemia. Leukemia 2006;20:365–8.PubMedCrossRefGoogle Scholar
  3. 3.
    De Lima M, Bonamino M, Vasconcelos Z. 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;27:73–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Huang XJ, Chang YJ, Zhao XY. In vivo induction of T-cell hyporesponsiveness and alteration of immunological cells of bone marrow grafts using granulocyte colony-stimulating factor. Haematologica 2004;89:1517–24.Google Scholar
  5. 5.
    Chen SH, Li X, Huang XJ. Effect of recombinant granulocyte colony-stimulating factor on T-lymphocyte function and the mechanism of this effect. Int J Hematol. 2004;79:178–84.PubMedCrossRefGoogle Scholar
  6. 6.
    Mengarelli A, Iori A, Guglielmi C. Standard versus alternative myeloablative conditioning regimens in allogeneic hematopoietic stem cell transplantation for high-risk acute leukemia. Haematologica 2002;87:52–8.PubMedGoogle Scholar
  7. 7.
    Zhou J, Guo NL, Zheng H. Comparison of two conditioning regimens in allogeneic bone marrow transplantation. Chin J Hematol. 1996;17:64–6.Google Scholar
  8. 8.
    Devergie A. Graft vs. host disease. In: Apperley J, Carreras E, Gluckman E, Gratwohl A, Masszi T, editors. Haematopoietic stem cell transplantation: the EBMT handbook. Rev ed. Paris, France: European School of Hematology; 2004. p. 168–9.Google Scholar
  9. 9.
    Durnam DM, Anders KR, Fisher L. Analysis of the origin of marrow cells in bone marrow transplant recipients using a Y-chromosome-specific in situ hybridization assay. Blood 1989;74:2220–6.PubMedGoogle Scholar
  10. 10.
    Anslinger K, Rolf B, Keil W. Evaluation and application of the AmpF/STR profiler plus PCR amplification kit in a Bavarian population sample. Int J Legal Med. 2001;114:278–80.PubMedCrossRefGoogle Scholar
  11. 11.
    Edenfield WJ, Gore SD. Stage-specific application of allogeneic and autologous marrow transplantation in the management of acute myeloid leukemia. Semin Oncol. 1999;26:21–34.PubMedGoogle Scholar
  12. 12.
    Robak T, Wrzesien-Kus A. The search for optimal treatment in relapsed and refractory acute myeloid leukemia. Leuk Lymphoma. 2002;43:281–91.PubMedCrossRefGoogle Scholar
  13. 13.
    Frassoni F. Stem cell transplantation in adults: acute leukemia. In: Apperley J, Carreras E, Gluckman E, Gratwohl A, Masszi T, editors. Haematopoietic stem cell transplantation: the EBMT handbook. Rev ed. Paris, France: European School of Hematology; 2004. p. 239–54.Google Scholar
  14. 14.
    Biggs JC, Horowitz MM, Gale RP. Bone marrow transplants may cure patients with acute leukemia never achieving remission with chemotherapy. Blood 1992;80:1090–3.PubMedGoogle Scholar
  15. 15.
    Ringden O, Horowitz M, Gale RP. Outcome after allogeneic bone marrow transplant for leukemia in older adults. JAMA 1993;270:57–60.PubMedCrossRefGoogle Scholar
  16. 16.
    Singhal S, Powles R, Henslee-Downey PJ. Allogeneic transplantation from HLA-matched sibling or partially HLA-mismatched related donors for primary refractory acute leukemia. Bone Marrow Transplant. 2002;29:291–5.PubMedCrossRefGoogle Scholar
  17. 17.
    Alessandrino EP, Bernasconi P, Caldera D. Chemotherapy and donor peripheral blood progenitor cells for acute leukemia in early relapse after allogeneic bone marrow transplantation. Bone Marrow Transplant. 1999;23:607–12.PubMedCrossRefGoogle Scholar
  18. 18.
    Slavin S, Naparstek E, Nagler A. Allogeneic cell therapy with donor peripheral blood cells and recombinant human interleukin-2 to treat leukemia relapse after allogeneic bone marrow transplantation. Blood 1996;87:2195–204.PubMedGoogle Scholar
  19. 19.
    Levine JE, Braun T, Penza SL. Prospective trial of chemotherapy and donor leukocyte infusions for relapse of advanced myeloid malignancies after allogeneic stem-cell transplantation. J Clin Oncol. 2002;20:405–12.PubMedCrossRefGoogle Scholar
  20. 20.
    Kolb HJ, Schattenberg A, Goldman JM. 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;86:2041–50.PubMedGoogle Scholar
  21. 21.
    Huang XJ, Liu DH, Liu KY. Donor lymphocyte infusion for the treatment of leukemia relapse after HLA-mismatched/haploidentical T-cell-replete hematopoietic stem cell transplantation. Haematologica 2007;92:414–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Sohn SK, Jung JT, Kim DH, Lee NY, Seo KW, Chae YS, et al. Prophylactic growth factor-mobilized donor lymphocyte infusion using cells reserved at the time of transplantation after allogeneic peripheral blood stem cell transplantation in patients with high-risk hematologic malignancies. Cancer 2002;94:18–24.PubMedCrossRefGoogle Scholar
  23. 23.
    Huang XJ, Chang YJ, Zhao XY. Maintaining hyporesponsiveness and polarization potential of T cells after in vitro mixture of G-CSF mobilized peripheral blood grafts and G-CSF primed bone marrow grafts in different proportions. Transplant Immunol. 2007;17:193–7.CrossRefGoogle Scholar
  24. 24.
    Pawson R, Potter MN, Theocharous P. Treatment of relapse after allogeneic bone marrow transplantation with reduced intensity conditioning (FLAG+/− Ida) and second allogeneic stem cell transplant. Br J Haematol. 2001;115:622–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Michallet M, Thomas X, Vernant JP. Long-term outcome after allogeneic hematopoietic stem cell transplantation for advanced stage acute myeloblastic leukemia: a retrospective study of 379 patients reported to the Societe Francaise de Greffe de Moelle (SFGM). Bone Marrow Transplant. 2000;26:1157–63.PubMedCrossRefGoogle Scholar
  26. 26.
    Clift RA, Buckner CD, Appelbaum FR. Allogeneic marrow transplantation during untreated first relapse of acute myeloid leukemia. J Clin Oncol. 1992;10:1723–9.PubMedGoogle Scholar
  27. 27.
    Schmid C, Schleuning M, Schwerdtfeger R. Long-term survival in refractory acute myeloid leukemia after sequential treatment with chemotherapy and reduced-intensity conditioning for allogeneic stem cell transplantation. Blood 2006;108:1092–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Xiao-Jun Huang
    • 1
  • Yu Wang
    • 1
  • Dai-Hong Liu
    • 1
  • Lan-Ping Xu
    • 1
  • Huan Chen
    • 1
  • Yu-Hong Chen
    • 1
  • Wei Han
    • 1
  • Hong-Xia Shi
    • 1
  • Kai-Yan Liu
    • 1
  1. 1.Peking University Institute of HematologyPeople’s HospitalBeijingPeople’s Republic of China

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