Current Hematologic Malignancy Reports

, Volume 2, Issue 3, pp 202–207

Perspective on the role of haploidentical transplantation in the management of hematologic malignancies: Why do it?

Article

Abstract

Haploidentical hematopoietic stem cell transplantation (HSCT) using mismatched family member donors has historically been complicated by high rates of nonrelapse toxicity and the need for laboratory expertise in depleting grafts of T lymphocytes. Over the past decade, improvements in supportive care, the increased use of peripheral-blood stem cell grafts, and improved T-cell depletion techniques have reduced the incidence of graft failure and lowered the rate of nonrelapse mortality. In addition, clinical studies have demonstrated that the donor-recipient mismatch may be beneficial in this setting, stimulating an immunologic cell-mediated antileukemia effect that results in lower disease recurrence rates. All of these advances have led to improvements in outcomes following haploidentical HSCT, making it an attractive option available to some patients. Because most patients do not have a matched related donor available and time to identify an unrelated donor may be excessive, haploidentical HSCT is a potentially curative option for these patients.

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References and Recommended Reading

  1. 1.
    Henslee-Downey PJ: Haploidentical transplantation. Cancer Treat Res 1999, 101:53–77.PubMedGoogle Scholar
  2. 2.
    Curtis RE, Travis LB, Rowlings PA, et al.: Risk of lymphoproliferative disorders after bone marrow transplantation: a multi-institutional study. Blood 1999, 94:2208–2216.PubMedGoogle Scholar
  3. 3.
    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.PubMedGoogle Scholar
  4. 4.
    Henslee-Downey PJ: Allogeneic transplantation across major HLA barriers. Best Pract Res Clin Haematol 2001, 14:741–754.PubMedCrossRefGoogle Scholar
  5. 5.
    Chiang KY, Van Rhee F, Godder K, et al.: Allogeneic bone marrow transplantation from partially mismatched related donors as therapy for primary induction failure acute myeloid leukemia. Bone Marrow Transplant 2001, 27:507–510.PubMedCrossRefGoogle Scholar
  6. 6.
    Mehta J, Singhal S, Gee AP, et al.: Bone marrow transplantation from partially HLA-mismatched family donors for acute leukemia: single-center experience of 201 patients. Bone Marrow Transplant 2004, 33:389–396.PubMedCrossRefGoogle Scholar
  7. 7.
    Singhal S, Powles R, Henslee-Downey PJ, et al.: Allogeneic transplantation from HLA-matched sibling or partially HLA-mismatched related donors for primary refractory acute leukemia. Bone Marrow Transplant 2002, 29:291–295.PubMedCrossRefGoogle Scholar
  8. 8.
    Leung W, Iyengar R, Turner V, et al.: Determinants of antileukemia effects of allogeneic NK cells. J Immunol 2004, 172:644–650.PubMedGoogle Scholar
  9. 9.
    Ichinohe T, Uchiyama T, Shimazaki C, et al.: Feasibility of HLA-haploidentical hematopoietic stem cell transplantation between noninherited maternal antigen (NIMA)-mismatched family members linked with long-term fetomaternal microchimerism. Blood 2004, 104:3821–3828.PubMedCrossRefGoogle Scholar
  10. 10.
    Lang P, Handgretinger R, Niethammer D, et al.: Transplantation of highly purified CD34+ progenitor cells from unrelated donors in pediatric leukemia. Blood 2003, 101:1630–1636.PubMedCrossRefGoogle Scholar
  11. 11.
    Handgretinger R, Klingebiel T, Lang P, et al.: Megadose transplantation of highly purified haploidentical stem cells: current results and future prospects. Pediatr Transplant 2003, 7(Suppl 3):51–55.PubMedCrossRefGoogle Scholar
  12. 12.
    Kasow KA, Leung W, Horwitz EM, et al.: EBV lymphoproliferative disease of host origin after haploidentical stem cell transplantation. Pediatr Blood Cancer 2007, In press.Google Scholar
  13. 13.
    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.PubMedCrossRefGoogle Scholar
  14. 14.
    Aversa F, Terenzi A, Tabilio A, et al.: Full haplotype mismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse. J Clin Oncol 2005, 23:3447–3454.PubMedCrossRefGoogle Scholar
  15. 15.
    Marks DI, Khattry N, Cummins M, et al.: Haploidentical stem cell transplantation for children with acute leukaemia. Br J Haematol 2006, 134:196–201.PubMedCrossRefGoogle Scholar
  16. 16.
    Lang P, Bader P, Schumm M, et al.: Transplantation of a combination of CD133+ and CD34+ selected progenitor cells from alternative donors. Br J Haematol 2004, 124:72–79.PubMedCrossRefGoogle Scholar
  17. 17.
    Lang P, Klingebiel T, Schumm M, et al.: Correction of persistent thrombocytopenia by a boost of CD133+ selected stem cells in a patient transplanted for Wiskott-Aldrich syndrome 10 years ago. Bone Marrow Transplant 2004, 33:879–880.PubMedCrossRefGoogle Scholar
  18. 18.
    Gordon PR, Leimig T, Mueller I, et al.: A large-scale method for T cell depletion: towards graft engineering of mobilized peripheral blood stem cells. Bone Marrow Transplant 2002, 30:69–74.PubMedCrossRefGoogle Scholar
  19. 19.
    Hale GA, Kasow KA, Gan K, et al.: Haploidentical stem cell transplantation with CD3 depleted mobilized peripheral blood stem cell grafts for children with hematologic malignancies [abstract]. Blood (ASH Annual Meeting Abstracts) 2005, 106:Abstract 2910.Google Scholar
  20. 20.
    Hale GA, Kasow KA, Madden R, et al.: Mismatched family member donor transplantation for patients with refractory hematologic malignancies: long-term follow-up of a prospective clinical trial [abstract]. Blood (ASH Annual Meeting Abstracts) 2006, 108:Abstract 3137.Google Scholar
  21. 21.
    Barfield RC, Otto M, Houston J, et al.: A one-step large-scale method for T-and B-cell depletion of mobilized PBSC for allogeneic transplantation. Cytotherapy 2004, 6:1–6.PubMedCrossRefGoogle Scholar
  22. 22.
    Guinan EC, Boussiotis VA, Neuberg D, et al.: Transplantation of anergic histoincompatible bone marrow allografts. N Engl J Med 1999, 340:1704–1714.PubMedCrossRefGoogle Scholar
  23. 23.
    Rizzieri DA, Koh LP, Long GD, et al.: Partially matched, nonmyeloablative allogeneic transplantation: clinical outcomes and immune reconstitution. J Clin Oncol 2007, 25:690–697.PubMedCrossRefGoogle Scholar
  24. 24.
    Klingebiel T, Handgretinger R, Lang P, et al.: Haploidentical transplantation for acute lymphoblastic leukemia in childhood. Blood Rev 2004, 18:181–192.PubMedCrossRefGoogle Scholar
  25. 25.
    Bader P, Kreyenberg H, Hoelle W, et al.: Increasing mixed chimerism is an important prognostic factor for unfavorable outcome in children with acute lymphoblastic leukemia after allogeneic stem-cell transplantation: possible role for preemptive immunotherapy? J Clin Oncol 2004, 22:1696–1705.PubMedCrossRefGoogle Scholar
  26. 26.
    Bader P, Kreyenberg H, Hoelle W, et al.: Increasing mixed chimerism defines a high-risk group of childhood acute myelogenous leukemia patients after allogeneic stem cell transplantation where pre-emptive immunotherapy may be effective. Bone Marrow Transplant 2004, 33:815–821.PubMedCrossRefGoogle Scholar
  27. 27.
    Lang P, Greil J, Muller I, et al.: Retransplantation with stem cells from mismatched related donors after graft rejection in pediatric patients [abstract]. Blood 2006, 108:837a.Google Scholar
  28. 28.
    Lang P, Greil J, Bader P, et al.: Long-term outcome after haploidentical stem cell transplantation in children. Blood Cells Mol Dis 2004, 33:281–287.PubMedCrossRefGoogle Scholar
  29. 29.
    Otto M, Barfield RC, Iyengar R, et al.: Human γδ T cells from G-CSF-mobilized donors retain strong tumoricidal activity and produce immunomodulatory cytokines after clinical-scale isolation. J Immunother 2005, 28:73–78.PubMedCrossRefGoogle Scholar
  30. 30.
    Chen X, Hale GA, Barfield R, et al.: Rapid immune reconstitution after a reduced-intensity conditioning regimen and a CD3-depleted haploidentical stem cell graft for paediatric refractory hematological malignancies. Br J Haematol 2006, 135:524–532.PubMedCrossRefGoogle Scholar
  31. 31.
    Min D, Taylor PA, Panoskaltsis-Mortari A, et al.: Protection from thymic epithelial cell injury by keratinocyte growth factor: a new approach to improve thymic and peripheral T-cell reconstitution after bone marrow transplantation. Blood 2002, 99:4592–4600.PubMedCrossRefGoogle Scholar
  32. 32.
    Amrolia PJ, Muccioli-Casadei G, Huls H, et al.: Adoptive immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical stem cell transplant. Blood 2006, 108:1797–1808.PubMedCrossRefGoogle Scholar
  33. 33.
    Yusuf U, Hale GA, Carr J, et al.: Cidofovir for the treatment of adenoviral infection in pediatric hematopoietic stem cell transplant patients. Transplantation 81:1398–1404.Google Scholar
  34. 34.
    Howden BP, Michaelides A, Spelman DW, et al.: Cytomegalovirus viral load monitoring after allogeneic bone marrow transplantation in patients receiving antiviral prophylaxis. Bone Marrow Transplant 2003, 32:795–800.PubMedCrossRefGoogle Scholar
  35. 35.
    Kuehnle I, Huls MH, Liu Z, et al.: CD20 monoclonal antibody (rituximab) for therapy of Epstein-Barr virus lymphoma after hemopoietic stem-cell transplantation. Blood 2000, 95:1502–1505.PubMedGoogle Scholar
  36. 36.
    Larocca A, Piaggio G, Podesta M, et al.: Boost of CD34+-selected peripheral blood cells without further conditioning in patients with poor graft function following allogeneic stem cell transplantation. Haematologica 2006, 91:935–940.PubMedGoogle Scholar
  37. 37.
    Lewalle P, Triffet A, Delforge A, et al.: Donor lymphocyte infusions in adult haploidentical transplant: a dose finding study. Bone Marrow Transplant 2003, 31:39–44.PubMedCrossRefGoogle Scholar
  38. 38.
    Leung W, Iyengar R, Triplett B, et al.: Comparison of killer Ig-like receptor genotyping and phenotyping for selection of allogeneic blood stem cell donors. J Immunol 2005, 174:6540–6545.PubMedGoogle Scholar
  39. 39.
    Passweg JR, Stern M, Koehl U, et al.: Use of natural killer cells in hematopoetic stem cell transplantation. Bone Marrow Transplant 2005, 35:637–643.PubMedCrossRefGoogle Scholar
  40. 40.
    Miller JS, Soignier Y, Panoskaltsis-Mortari A, et al.: Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood 2005, 105:3051–3057.PubMedCrossRefGoogle Scholar
  41. 41.
    Leung W, Iyengar R, Leimig T, et al.: Phenotype and function of human natural killer cells purified by using a clinical-scale immunomagnetic method. Cancer Immunol Immunother 2005, 54:389–394.PubMedCrossRefGoogle Scholar

Copyright information

© Current Medicine Group LLC 2007

Authors and Affiliations

  1. 1.Division of Bone Marrow TransplantationSt. Jude Children’s Research HospitalMemphisUSA

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