Biology of Blood and Marrow Transplantation
Volume 16, Issue 3 , Pages 384-394 , March 2010

Low-Dose Total Body Irradiation and Fludarabine Conditioning for HLA Class I-Mismatched Donor Stem Cell Transplantation and Immunologic Recovery in Patients with Hematologic Malignancies: A Multicenter Trial

  • Hirohisa Nakamae

      Affiliations

    • Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
  • ,
  • Barry E. Storer

      Affiliations

    • Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
    • University of Washington School of Medicine, Seattle, Washington
  • ,
  • Rainer Storb

      Affiliations

    • Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
    • University of Washington School of Medicine, Seattle, Washington
  • ,
  • Jan Storek

      Affiliations

    • Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
    • University of Calgary, Calgary, Alberta, Canada
  • ,
  • Thomas R. Chauncey

      Affiliations

    • Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
    • University of Washington School of Medicine, Seattle, Washington
    • Veterans Affairs Puget Sound Health Care System, Seattle, Washington
  • ,
  • Michael A. Pulsipher

      Affiliations

    • University of Utah, Salt Lake City, Utah
  • ,
  • Finn B. Petersen

      Affiliations

    • Intermountain Blood and Marrow Transplant Program, Salt Lake City, Utah
  • ,
  • James C. Wade

      Affiliations

    • Medical College of Wisconsin, Milwaukee, Wisconsin
  • ,
  • Michael B. Maris

      Affiliations

    • Rocky Mountain Blood & Marrow Transplantation, Denver, Colorado
  • ,
  • Benedetto Bruno

      Affiliations

    • University of Torino, Torino, Italy
  • ,
  • Jens Panse

      Affiliations

    • University of Hamburg, Hamburg, Germany
  • ,
  • Effie Petersdorf

      Affiliations

    • Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
    • University of Washington School of Medicine, Seattle, Washington
  • ,
  • Ann Woolfrey

      Affiliations

    • Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
    • University of Washington School of Medicine, Seattle, Washington
  • ,
  • David G. Maloney

      Affiliations

    • Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
    • University of Washington School of Medicine, Seattle, Washington
  • ,
  • Brenda M. Sandmaier

      Affiliations

    • Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
    • University of Washington School of Medicine, Seattle, Washington
    • Corresponding Author InformationCorrespondence and reprint requests: Brenda M. Sandmaier, MD, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, Mail Stop D1-100, PO Box 19024, Seattle, WA 98109-1024.

Received 22 September 2009 ,Accepted 3 November 2009.

References 

  1. Finke J, Schmoor C, Lang H, et al. Matched and mismatched allogeneic stem-cell transplantation from unrelated donors using combined graft-versus-host disease prophylaxis including rabbit anti-T lymphocyte globulin. J Clin Oncol. 2003;21:506–513
  2. Sedlacek P, Formankova R, Keslova P, et al. Low mortality of children undergoing hematopoietic stem cell transplantation from 7 to 8/10 human leukocyte antigen allele-matched unrelated donors with the use of antithymocyte globulin. Bone Marrow Transplant. 2006;38:745–750
  3. Morishima Y, Sasazuki T, Inoko H, et al. The clinical significance of human leukocyte antigen (HLA) allele compatibility in patients receiving a marrow transplant from serologically HLA-A-, HLA-B-, and HLA-DR-matched unrelated donors. Blood. 2002;99:4200–4206
  4. Petersdorf EW, Gooley TA, Anasetti C, et al. Optimizing outcome after unrelated marrow transplantation by comprehensive matching of HLA class I and II alleles in the donor and recipient. Blood. 1998;92:3515–3520
  5. Petersdorf EW, Hansen JA, Martin PJ, et al. Major histocompatibility complex class I alleles and antigens in hematopoietic cell transplantation. N Engl J Med. 2001;345:1794–1800
  6. Storb R, Yu C, Wagner JL, et al. Stable mixed hematopoietic chimerism in DLA-identical littermate dogs given sublethal total body irradiation before and pharmacological immunosuppression after marrow transplantation. Blood. 1997;89:3048–3054
  7. Maris MB, Niederwieser D, Sandmaier BM, et al. HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies. Blood. 2003;102:2021–2030
  8. Niederwieser D, Maris M, Shizuru JA, et al. Low-dose total body irradiation (TBI) and fludarabine followed by hematopoietic cell transplantation (HCT) from HLA-matched or mismatched unrelated donors and postgrafting immunosuppression with cyclosporine and mycophenolate mofetil (MMF) can induce durable complete chimerism and sustained remissions in patients with hematological diseases. Blood. 2003;101:1620–1629
  9. McSweeney PA, Niederwieser D, Shizuru JA, et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood. 2001;97:3390–3400
  10. Feinstein L, Sandmaier B, Maloney D, et al. Nonmyeloablative hematopoietic cell transplantation: replacing high-dose cytotoxic therapy by the graft-versus-tumor effect. Ann NY Acad Sci. 2001;938:328–339
  11. Maris MB, Sandmaier BM, Storer BE, et al. Allogeneic hematopoietic cell transplantation after fludarabine and 2 Gy total body irradiation for relapsed and refractory mantle cell lymphoma. Blood. 2004;104:3535–3542
  12. Sorror ML, Maris MB, Sandmaier BM, et al. Hematopoietic cell transplantation after nonmyeloablative conditioning for advanced chronic lymphocytic leukemia. J Clin Oncol. 2005;23:3819–3829
  13. Hansen JA, Mickelson EM, Choo SY, et al. Clinical bone marrow transplantation: donor selection and recipient monitoring. In:  Rose NR,  De Macario EC,  Fahey JL, et al. editor. Manual of Clinical Laboratory Immunology. Washington, DC: American Society for Microbiology; 1992;p. 850–866
  14. Dupont B, Yang SY. Histocompatibility. In:  Forman SJ,  Blume KG,  Thomas ED editor. Bone Marrow Transplantation. Boston: Blackwell Scientific; 1994;p. 22–40
  15. Petersdorf EW, Smith AG, Mickelson EM, et al. Ten HLA-DR4 alleles defined by sequence polymorphisms within the DRB1 first domain. Immunogenetics. 1991;33:267–275
  16. Petersdorf EW, Anasetti C, Martin PJ, et al. Limits of HLA mismatching in unrelated hematopoietic cell transplantation. Blood. 2004;104:2976–2980
  17. Anasetti C, Amos D, Beatty PG, et al. Effect of HLA compatibility on engraftment of bone marrow transplants in patients with leukemia or lymphoma. N Engl J Med. 1989;320:197–204
  18. Kahl C, Storer BE, Sandmaier BM, et al. Relapse risk among patients with malignant diseases given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. Blood. 2007;110:2744–2748
  19. Sorror ML, Maris MB, Storb R, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106:2912–2919
  20. Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus conference on acute GVHD grading. Bone Marrow Transplant. 1995;15:825–828
  21. Sullivan KM, Agura E, Anasetti C, et al. Chronic graft-versus-host disease and other late complications of bone marrow transplantation. Semin Hematol. 1991;28:250–259
  22. Storek J, Dawson MA, Storer B, et al. Immune reconstitution after allogeneic marrow transplantation compared with blood stem cell transplantation. Blood. 2001;97:3380–3389
  23. Storek J, Zhao Z, Lin E, et al. Recovery from and consequences of severe iatrogenic lymphopenia (induced to treat autoimmune diseases). Clin Immunol. 2004;113:285–298
  24. Klein U, Kuppers R, Rajewsky K. Human IgM+IgD+ B cells, the major B cell subset in the peripheral blood, express V kappa genes with no or little somatic mutation throughout life. Eur J Immunol. 1993;23:3272–3277
  25. Suzuki I, Milner ECB, Glas AM, et al. Immunoglobulin heavy-chain variable region gene usage in bone marrow transplant recipients: lack of somatic mutation indicates a maturational arrest. Blood. 1996;87:1873–1880
  26. Klein U, Rajewsky K, Kuppers R. Human immunoglobulin (Ig)M+IgD+ peripheral blood B cells expressing the CD27 cell surface antigen carry somatically mutated variable region genes: CD27 as a general marker for somatically mutated (memory) B cells. J Exp Med. 1998;188:1679–1689
  27. Douek DC, McFarland RD, Keiser PH, et al. Changes in thymic function with age and during the treatment of HIV infection. Nature. 1998;396:690–695
  28. Dumont-Girard F, Roux E, van Lier RA, et al. Reconstitution of the T-cell compartment after bone marrow transplantation: restoration of the repertoire by thymic emigrants. Blood. 1998;92:4464–4471
  29. Storek J, Witherspoon RP, Storb R. T cell reconstitution after bone marrow transplantation into adult patients does not resemble T cell development in early life. Bone Marrow Transplant. 1995;16:413–425
  30. Okumura M, Fujii Y, Inada K, et al. Both CD45RA+ and CD45RA- subpopulations of CD8+ T cells contain cells with high levels of lymphocyte function-associated antigen-1 expression, a phenotype of primed T cells. J Immunol. 1993;150:429–437
  31. Okumura M, Fujii Y, Takeuchi Y, et al. Age-related accumulation of LFA-1high cells in a CD8+CD45RAhigh T cell population. Eur J Immunol. 1993;23:1057–1063
  32. Maris MB, Sandmaier BM, Storer BE, et al. Unrelated donor granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell transplantation after nonmyeloablative conditioning: the effect of postgrafting mycophenolate mofetil dosing. Biol Blood Marrow Transplant. 2006;12:454–465
  33. Sasazuki T, Juji T, Morishima Y, et al. Effect of matching of class I HLA alleles on clinical outcome after transplantation of hematopoietic stem cells from an unrelated donor. N Engl J Med. 1998;339:1177–1185
  34. Flomenberg N, Baxter-Lowe LA, Confer D, et al. Impact of HLA class I and class II high-resolution matching on outcomes of unrelated donor bone marrow transplantation: HLA-C mismatching is associated with a strong adverse effect on transplant outcome. Blood. 2004;104:1923–1930
  35. Greinix HT, Fae I, Schneider B, et al. Impact of HLA class I high-resolution mismatches on chronic graft-versus-host disease and survival of patients given hematopoietic stem cell grafts from unrelated donors. Bone Marrow Transplant. 2005;35:57–62
  36. Kernan NA, Bartsch G, Ash RC, et al. Analysis of 462 transplantations from unrelated donors facilitated by the National Marrow Donor Program. N Engl J Med. 1993;328:593–602
  37. McGlave P, Bartsch G, Anasetti C, et al. Unrelated donor marrow transplantation therapy for chronic myelogenous leukemia: initial experience of the National Marrow Donor Program. Blood. 1993;81:543–550
  38. Szydlo R, Goldman JM, Klein JP, et al. Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings. J Clin Oncol. 1997;15:1767–1777
  39. Nash RA, Antin JH, Karanes C, et al. Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors. Blood. 2000;96:2062–2068
  40. Das Gupta EP, Russell NH, Shaw BE, et al. Long-term outcome of unrelated donor transplantation for AML using myeloablative conditioning incorporating pretransplant alemtuzumab. Biol Blood Marrow Transplant. 2007;13:724–733
  41. Thomson KJ, Morris EC, Bloor A, et al. Favorable long-term survival after reduced-intensity allogeneic transplantation for multiple-relapse aggressive non-Hodgkin's lymphoma. J Clin Oncol. 2009;27:426–432
  42. Kanda Y, Oshima K, Asano-Mori Y, et al. In vivo alemtuzumab enables haploidentical human leukocyte antigen-mismatched hematopoietic stem cell transplantation without ex vivo graft manipulation. Transplantation. 2005;79:1351–1357
  43. Chakraverty R, Peggs K, Chopra R, et al. Limiting transplantation-related mortality following unrelated donor stem cell transplantation by using a nonmyeloablative conditioning regimen. Blood. 2002;99:1071–1078
  44. Luznik L, O'Donnell PV, Symons HJ, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, post-transplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008;14:641–650
  45. Baron F, Maris MB, Sandmaier BM, et al. Graft-versus-tumor effects after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning. J Clin Oncol. 2005;23:1993–2003
  46. Bertz H, Spyridonidis A, Wasch R, Grullich C, Egger M, Finke J. A novel GVHD-prophylaxis with low-dose alemtuzumab in allogeneic sibling or unrelated donor hematopoetic cell transplantation: the feasibility of deescalation. Biol Blood Marrow Transplant. 2009;15:1563–1570
  47. Ho VT, Aldridge J, Kim HT, et al. Comparison of tacrolimus and sirolimus (Tac/Sir) versus tacrolimus, sirolimus, and mini-methotrexate (Tac/Sir/MTX) as acute graft-versus-host disease prophylaxis after reduced-intensity conditioning allogeneic peripheral blood stem cell transplantation. Biol Blood Marrow Transplant. 2009;15:844–850
  48. Baron F, Storer B, Maris MB, et al. Unrelated donor status and high donor age independently affect immunologic recovery after nonmyeloablative conditioning. Biol Blood Marrow Transplant. 2006;12:1176–1187
  49. Storek J, Witherspoon RP, Webb D, et al. Lack of B cell precursors in marrow transplant recipients with chronic graft-versus-host disease. Am J Hematol. 1996;52:82–89
  50. Storek J, Wells D, Dawson MA, et al. Factors influencing B-lymphopoiesis after allogeneic hematopoietic cell transplantation. Blood. 2001;98:489–491

 Financial disclosure: See Acknowlegments on page 392.

PII: S1083-8791(09)00521-7

doi: 10.1016/j.bbmt.2009.11.004

Biology of Blood and Marrow Transplantation
Volume 16, Issue 3 , Pages 384-394 , March 2010