Biology of Blood and Marrow Transplantation
Volume 16, Issue 1, Supplement , Pages S68-S74 , January 2010

Preservation of Immune Repertoire by Selective Depletion of Haploidentical Grafts

  • Eva Guinan

      Affiliations

    • Dana-Farber Cancer Institute, Boston, Massachusetts
    • ,
  • Leo Luzmik

      Affiliations

    • Sidney Kimmell Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland
    • ,
  • Rupert Handgretinger

      Affiliations

    • Children's University Hospital, University of Tuebingen, Germany
    • ,
  • Ann Woolfrey

      Affiliations

    • Fred Hutchinson Cancer Research Center, Seattle, Washington
    • Corresponding Author InformationCorrespondence and reprint requests: Ann Woolfrey, MD, Clinical Research Division Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109.

References 

  1. Kernan NA, Collins NH, Juliano L, Cartagena T, Dupont B, O'Reilly RJ. Clonable T lymphocytes in T cell-depleted bone marrow transplants correlate with development of graft-v-host disease. Blood. 1986;68:770–773
  2. Kernan NA, Flomenberg N, Dupont B, O'Reilly RJ. Graft rejection in recipients of T-cell-depleted HLA-nonidentical marrow transplants for leukemia. Identification of host-derived antidonor allocytotoxic T lymphocytes. Transplantation. 1987;43:842–847
  3. Godder kt, Hazlett LJ, Abhyankar SH, et al. Partially mismatched related-donor bone marrow transplantation for pediatric patients with acute leukemia: younger donors and absence of peripheral blasts improve outcome. J Clin Oncol. 2000;(18):1856–1866
  4. Aversa F, Tabilio A, Velardi A, et al. Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. N Engl J Med. 1998;339:1186–1193
  5. Keever CA, Small TN, Flomenberg N, et al. Immune reconstitution following bone marrow transplantation: comparison of recipients of T-cell depleted marrow with recipients of conventional marrow grafts. Blood. 1989;73:1340–1350
  6. Davies JK, Koh MB, Lowdell MW. Antiviral immunity and T-regulatory cell function are retained after selective alloreactive T-cell depletion in both the HLA-identical and HLA-mismatched settings. Biol Blood Marrow Transplant. 2004;10:259–268
  7. Amrolia PJ, Muccioli-Casadei G, Yvon E, et al. Selective depletion of donor alloreactive T cells without loss of antiviral or antileukemic responses. Blood. 2003;102:2292–2299
  8. Gribben JG, Guinan EC, Boussiotis VA, et al. Complete blockade of B7 mediated costimulation is necessary to induce human alloantigen specific anergy: a method to ameliorate graft versus host disease and extend the donor pool. Blood. 1996;87:4887–4893
  9. Schwartz RH. Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. Cell. 1992;71:1065–1068
  10. Tan P, Anasetti C, Hansen JA, et al. Induction of alloantigen-specific hyporesponsiveness in human T lymphocytes by blocking interaction of CD28 with its natural ligand B7/BB1. J Exp Med. 1993;177:165–173
  11. Gimmi CD, Freeman GJ, Gribben JG, et al. B-cell surface antigen B7 provides a costimulatory signal that induces T cells to proliferate and secrete interleukin 2. Proc Natl Acad Sci USA. 1991;88:6575–6579
  12. Boussiotis VA, Barber DL, Lee BJ, Gribben JG, Freeman GJ, Nadler LM. Differential association of protein tyrosine kinases with the T cell receptor is linked to the induction of anergy and its prevention by B7 family mediated costimulation. J Exp Med. 1996;184:365–376
  13. Davies JK, Gribben JG, Brennan LL, Yuk D, Nadler LM, Guinan EC. Outcome of alloanergized haploidentical bone marrow transplantation after ex vivo costimulatory blockade: results of 2 phase 1 studies. Blood. 2008;112:2232–2241
  14. Guinan EC, Boussiotis VA, Neuberg D, et al. Transplantation of anergic histoincompatible bone marrow allografts. N Engl J Med. 1999;340:1704–1714
  15. Taylor PA, Friedman TM, Korngold R, Noelle RJ, Blazar BR. Tolerance induction of alloreactive T cells via ex vivo blockade of the CD40:CD40L costimulatory pathway results in the generation of a potent immune regulatory cell. Blood. 2002;99:4601–4609
  16. Berenbaum MC, Brown IN. Prolongation of homograft survival in mice with single doses of cyclophosphamide. Nature. 1963;200:84
  17. Mayumi H, Himeno K, Tokuda N, Nomoto K. Drug-induced tolerance to allografts in mice. VII. Optimal protocol and mechanism of cyclophosphamide-induced tolerance in an H-2 haplotype-identical strain combination. Transplant Proc. 1986;18:363–369
  18. Strauss G, Osen W, Debatin KM. Induction of apoptosis and modulation of activation and effector function in T cells by immunosuppressive drugs. Clin Exp Immunol. 2002;128:255–266
  19. Luznik L, Jalla S, Engstrom LW, Iannone R, Fuchs EJ. Durable engraftment of major histocompatibility complex-incompatible cells after nonmyeloablative conditioning with fludarabine, low-dose total body irradiation, and posttransplantation cyclophosphamide. Blood. 2001;98:3456–3464
  20. Santos GW, Tutschka PJ, Brookmeyer R, et al. Cyclosporine plus methylprednisolone versus cyclophosphamide plus methylprednisolone as prophylaxis for graft-versus-host disease: a randomized, double-blind study in patients undergoing allogeneic marrow transplantation. Clin Transplant. 1987;1:21–28
  21. Luznik L, Engstrom LW, Iannone R, Fuchs EJ. Posttransplantation cyclophosphamide facilitates engraftment of major histocompatibility complex-identical allogeneic marrow in mice conditioned with low-dose total body irradiation. Biol Blood Marrow Transplant. 2002;8:131–138
  22. Luznik L, O'Donnell PV, Symons HJ, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008;14:641–650
  23. O'Donnell PV, Luznik L, Jones RJ, et al. Nonmyeloablative bone marrow transplantation from partially HLA-mismatched related donors using posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2002;8:377–386
  24. Brodsky RA, Luznik L, Bolanos-Meade J, Leffell MS, Jones RJ, Fuchs EJ. Reduced intensity HLA-haploidentical BMT with post transplantation cyclophosphamide in nonmalignant hematologic diseases. Bone Marrow Transplant. 2008;42:523–527
  25. Handgretinger R, Klingebiel T, Lang P, et al. Megadose transplantation of purified peripheral blood CD34(+) progenitor cells from HLA-mismatched parental donors in children. Bone Marrow Transplant. 2001;27:777–783
  26. Ruggeri L, Capanni M, Urbani E, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002;295:2097–2100
  27. Schumm M, Feuchtinger T, Pfeiffer M, et al. Flow cytometry with anti HLA-antibodies: a simple but highly sensitive method for monitoring chimerism and minimal residual disease after HLA-mismatched stem cell transplantation. Bone Marrow Transplant. 2007;39:767–773
  28. Chaleff S, Otto M, Barfield RC, et al. A large-scale method for the selective depletion of alphabeta T lymphocytes from PBSC for allogeneic transplantation. Cytotherapy. 2007;9:746–754
  29. Meeh PF, King M, O'Brien RL, et al. Characterization of the gammadelta T cell response to acute leukemia. Cancer Immunol Immunother. 2006;55:1072–1080
  30. Godder KT, Henslee-Downey PJ, Mehta J, et al. Long term disease-free survival in acute leukemia patients recovering with increased gammadelta T cells after partially mismatched related donor bone marrow transplantation. Bone Marrow Transplant. 2007;39:751–757

 Financial disclosure: See Acknowledgments on page S74.

PII: S1083-8791(09)00532-1

doi: 10.1016/j.bbmt.2009.11.015

Biology of Blood and Marrow Transplantation
Volume 16, Issue 1, Supplement , Pages S68-S74 , January 2010

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