Table of Contents Author Guidelines Submit a Manuscript
Advances in Hematology
Volume 2016 (2016), Article ID 1423493, 8 pages
http://dx.doi.org/10.1155/2016/1423493
Review Article

Haploidentical Hematopoietic Stem Cell Transplantation: Expanding the Horizon for Hematologic Disorders

1Aga Khan University, Karachi 74800, Pakistan
2Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute, Durham, NC 27710, USA

Received 10 November 2015; Accepted 10 January 2016

Academic Editor: Suparno Chakrabarti

Copyright © 2016 Mohammad Faizan Zahid and David Alan Rizzieri. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. S. Ciavarella, A. Milano, F. Dammacco, and F. Silvestris, “Targeted therapies in cancer,” BioDrugs, vol. 24, no. 2, pp. 77–88, 2010. View at Publisher · View at Google Scholar · View at Scopus
  2. E. A. Copelan, “Hematopoietic stem-cell transplantation,” The New England Journal of Medicine, vol. 354, no. 17, pp. 1813–1826, 2006. View at Publisher · View at Google Scholar · View at Scopus
  3. L. Gragert, M. Eapen, E. Williams et al., “HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry,” The New England Journal of Medicine, vol. 371, no. 4, pp. 339–348, 2014. View at Publisher · View at Google Scholar · View at Scopus
  4. J. Dehn, M. Arora, S. Spellman et al., “Unrelated donor hematopoietic cell transplantation: factors associated with a better HLA match,” Biology of Blood and Marrow Transplantation, vol. 14, no. 12, pp. 1334–1340, 2008. View at Publisher · View at Google Scholar · View at Scopus
  5. M. Shabbir-Moosajee, L. Lombardi, and S. O. Ciurea, “An overview of conditioning regimens for haploidentical stem cell transplantation with post-transplantation cyclophosphamide,” American Journal of Hematology, vol. 90, no. 6, pp. 541–548, 2015. View at Publisher · View at Google Scholar
  6. K. K. Ballen, E. Gluckman, and H. E. Broxmeyer, “Umbilical cord blood transplantation: the first 25 years and beyond,” Blood, vol. 122, no. 4, pp. 491–498, 2013. View at Publisher · View at Google Scholar · View at Scopus
  7. N. J. Chao, L.-P. Koh, G. D. Long et al., “Adult recipients of umbilical cord blood transplants after nonmyeloablative preparative regimens,” Biology of Blood and Marrow Transplantation, vol. 10, no. 8, pp. 569–575, 2004. View at Publisher · View at Google Scholar · View at Scopus
  8. M. J. Laughlin, J. Barker, B. Bambach et al., “Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors,” The New England Journal of Medicine, vol. 344, no. 24, pp. 1815–1822, 2001. View at Publisher · View at Google Scholar · View at Scopus
  9. G. D. Long, M. Laughlin, B. Madan et al., “Unrelated umbilical cord blood transplantation in adult patients,” Biology of Blood and Marrow Transplantation, vol. 9, no. 12, pp. 772–780, 2003. View at Publisher · View at Google Scholar · View at Scopus
  10. D. A. Rizzieri, G. D. Long, J. J. Vredenburgh et al., “Successful allogeneic engraftment of mismatched unrelated cord blood following a nonmyeloablative preparative regimen,” Blood, vol. 98, no. 12, pp. 3486–3488, 2001. View at Publisher · View at Google Scholar · View at Scopus
  11. J. N. Barker, T. P. Krepski, T. E. DeFor, S. M. Davies, J. E. Wagner, and D. J. Weisdorf, “Searching for unrelated donor hematopoietic stem cells: availability and speed of umbilical cord blood versus bone marrow,” Biology of Blood and Marrow Transplantation, vol. 8, no. 5, pp. 257–260, 2002. View at Publisher · View at Google Scholar · View at Scopus
  12. J. Munoz, N. Shah, K. Rezvani et al., “Concise review: umbilical cord blood transplantation: past, present, and future,” Stem Cells Translational Medicine, vol. 3, no. 12, pp. 1435–1443, 2014. View at Publisher · View at Google Scholar · View at Scopus
  13. U. D. Bayraktar, R. E. Champlin, and S. O. Ciurea, “Progress in haploidentical stem cell transplantation,” Biology of Blood and Marrow Transplantation, vol. 18, no. 3, pp. 372–380, 2012. View at Publisher · View at Google Scholar · View at Scopus
  14. L. Garderet, N. Dulphy, C. Douay et al., “The umbilical cord blood αβ T-cell repertoire: characteristics of a polyclonal and naive but completely formed repertoire,” Blood, vol. 91, no. 1, pp. 340–346, 1998. View at Google Scholar · View at Scopus
  15. E. W. Petersdorf, T. A. Gooley, C. Anasetti et al., “Optimizing outcome after unrelated marrow transplantation by comprehensive matching of HLA class I and II alleles in the donor and recipient,” Blood, vol. 92, no. 10, pp. 3515–3520, 1998. View at Google Scholar · View at Scopus
  16. J. E. Wagner, J. Rosenthal, R. Sweetman et al., “Successful transplantation of HLA-matched and HLA-mismatched umbilical cord blood from unrelated donors: analysis of engraftment and acute graft- versus-host disease,” Blood, vol. 88, no. 3, pp. 795–802, 1996. View at Google Scholar · View at Scopus
  17. T. Bart, M. Boo, S. Balabanova et al., “Impact of selection of cord blood units from the United States and Swiss registries on the cost of banking operations,” Transfusion Medicine and Hemotherapy, vol. 40, no. 1, pp. 14–20, 2013. View at Publisher · View at Google Scholar · View at Scopus
  18. Y. Reisner, F. Aversa, and M. F. Martelli, “Haploidentical hematopoietic stem cell transplantation: state of art,” Bone Marrow Transplantation, vol. 50, supplement 2, pp. S1–S5, 2015. View at Publisher · View at Google Scholar
  19. J. A. Roth, M. E. Bensink, P. V. O'Donnell, E. J. Fuchs, M. Eapen, and S. D. Ramsey, “Design of a cost–effectiveness analysis alongside a randomized trial of transplantation using umbilical cord blood versus HLA-haploidentical related bone marrow in advanced hematologic cancer,” Journal of Comparative Effectiveness Research, vol. 3, no. 2, pp. 135–144, 2014. View at Publisher · View at Google Scholar · View at Scopus
  20. C. Anasetti, P. G. Beatty, R. Storb et al., “Effect of HLA incompatibility on graft-versus-host disease, relapse, and survival after marrow transplantation for patients with leukemia or lymphoma,” Human Immunology, vol. 29, no. 2, pp. 79–91, 1990. View at Publisher · View at Google Scholar · View at Scopus
  21. R. C. Ash, M. M. Horowitz, R. P. Gale et al., “Bone marrow transplantation from related donors other than HLA-identical siblings: effect of T cell depletion,” Bone Marrow Transplantation, vol. 7, no. 6, pp. 443–452, 1991. View at Google Scholar · View at Scopus
  22. Y. Kanda, S. Chiba, H. Hirai et al., “Allogeneic hematopoietic stem cell transplantation from family members other than HLA-identical siblings over the last decade (1991–2000),” Blood, vol. 102, no. 4, pp. 1541–1547, 2003. View at Publisher · View at Google Scholar · View at Scopus
  23. Y. Morishima, T. Yabe, K. Matsuo et al., “Effects of HLA allele and killer immunoglobulin-like receptor ligand matching on clinical outcome in leukemia patients undergoing transplantation with T-cell-replete marrow from an unrelated donor,” Biology of Blood and Marrow Transplantation, vol. 13, no. 3, pp. 315–328, 2007. View at Publisher · View at Google Scholar · View at Scopus
  24. R. Szydlo, J. M. Goldman, J. P. Klein et al., “Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings,” Journal of Clinical Oncology, vol. 15, no. 5, pp. 1767–1777, 1997. View at Google Scholar · View at Scopus
  25. T. Kawase, Y. Morishima, K. Matsuo et al., “High-risk HLA allele mismatch combinations responsible for severe acute graft-versus-host disease and implication for its molecular mechanism,” Blood, vol. 110, no. 7, pp. 2235–2241, 2007. View at Publisher · View at Google Scholar · View at Scopus
  26. L. Oevermann and R. Handgretinger, “New strategies for haploidentical transplantation,” Pediatric Research, vol. 71, no. 4, part 2, pp. 418–426, 2012. View at Publisher · View at Google Scholar · View at Scopus
  27. Y. Reisner, I. Ben-Bassat, D. Douer, A. Kaploon, E. Schwartz, and B. Ramot, “Demonstration of clonable alloreactive host T cells in a primate model for bone marrow transplantation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 83, no. 11, pp. 4012–4015, 1986. View at Publisher · View at Google Scholar · View at Scopus
  28. F. Aversa, A. Terenzi, A. Tabilio et al., “Full haplotype-mismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse,” Journal of Clinical Oncology, vol. 23, no. 15, pp. 3447–3454, 2005. View at Publisher · View at Google Scholar · View at Scopus
  29. C. Peters, S. Matthes-Martin, G. Fritsch et al., “Transplantation of highly purified peripheral blood CD34+ cells from HLA-mismatched parental donors in 14 children: evaluation of early monitoring of engraftment,” Leukemia, vol. 13, no. 12, pp. 2070–2078, 1999. View at Publisher · View at Google Scholar · View at Scopus
  30. Y. Reisner, N. Kapoor, D. Kirkpatrick et al., “Transplantation for severe combined immunodeficiency with HLA-A, B, D, DR incompatible parental marrow cells fractionated by soybean agglutinin and sheep red blood cells,” Blood, vol. 61, no. 2, pp. 341–348, 1983. View at Google Scholar · View at Scopus
  31. T. Klingebiel, J. Cornish, M. Labopin et al., “Results and factors influencing outcome after fully haploidentical hematopoietic stem cell transplantation in children with very high-risk acute lymphoblastic leukemia: impact of center size: an analysis on behalf of the Acute Leukemia and Pediatric Disease Working Parties of the European Blood and Marrow Transplant group,” Blood, vol. 115, no. 17, pp. 3437–3446, 2010. View at Publisher · View at Google Scholar · View at Scopus
  32. N. A. Kernan, C. Bordignon, C. A. Keever et al., “Graft failures after T cell depleted marrow transplants for leukemia: clinical and in vitro characteristics,” Transplantation Proceedings, vol. 19, no. 6, supplement 7, pp. 29–32, 1987. View at Google Scholar · View at Scopus
  33. R. C. Barfield, M. Otto, J. Houston et al., “A one-step large-scale method for T- and B-cell depletion of mobilized PBSC for allogeneic transplantation,” Cytotherapy, vol. 6, no. 1, pp. 1–6, 2004. View at Publisher · View at Google Scholar · View at Scopus
  34. W. Leung, “Use of NK cell activity in cure by transplant,” British Journal of Haematology, vol. 155, no. 1, pp. 14–29, 2011. View at Publisher · View at Google Scholar · View at Scopus
  35. C. Bottino, L. Moretta, D. Pende, M. Vitale, and A. Moretta, “Learning how to discriminate between friends and enemies, a lesson from natural killer cells,” Molecular Immunology, vol. 41, no. 6-7, pp. 569–575, 2004. View at Publisher · View at Google Scholar · View at Scopus
  36. A. Moretta, F. Locatelli, and L. Moretta, “Human NK cells: from HLA class I-specific killer Ig-like receptors to the therapy of acute leukemias,” Immunological Reviews, vol. 224, no. 1, pp. 58–69, 2008. View at Publisher · View at Google Scholar · View at Scopus
  37. W. Leung, R. Iyengar, V. Turner et al., “Determinants of antileukemia effects of allogeneic NK cells,” The Journal of Immunology, vol. 172, no. 1, pp. 644–650, 2004. View at Publisher · View at Google Scholar · View at Scopus
  38. L. Ruggeri, A. Mancusi, M. Capanni et al., “Donor natural killer cell allorecognition of missing self in haploidentical hematopoietic transplantation for acute myeloid leukemia: challenging its predictive value,” Blood, vol. 110, no. 1, pp. 433–440, 2007. View at Publisher · View at Google Scholar · View at Scopus
  39. F. Locatelli, D. Pende, R. Maccario, M. C. Mingari, A. Moretta, and L. Moretta, “Haploidentical hemopoietic stem cell transplantation for the treatment of high-risk leukemias: how NK cells make the difference,” Clinical Immunology, vol. 133, no. 2, pp. 171–178, 2009. View at Publisher · View at Google Scholar · View at Scopus
  40. R. Handgretinger, X. Chen, M. Pfeiffer et al., “Feasibility and outcome of reduced-intensity conditioning in haploidentical transplantation,” Annals of the New York Academy of Sciences, vol. 1106, pp. 279–289, 2007. View at Publisher · View at Google Scholar · View at Scopus
  41. J. M. Goldman, R. P. Gale, M. M. Horowitz et al., “Bone marrow transplantation for chronic myelogenous leukemia in chronic phase: increased risk for relapse associated with T-cell depletion,” Annals of Internal Medicine, vol. 108, no. 6, pp. 806–814, 1988. View at Publisher · View at Google Scholar · View at Scopus
  42. A. M. Marmont, M. M. Horowitz, R. P. Gale et al., “T-cell depletion of HLA-identical transplants in leukemia,” Blood, vol. 78, no. 8, pp. 2120–2130, 1991. View at Google Scholar · View at Scopus
  43. S. Chaleff, M. Otto, R. C. Barfield et al., “A large-scale method for the selective depletion of αβ T lymphocytes from PBSC for allogeneic transplantation,” Cytotherapy, vol. 9, no. 8, pp. 746–754, 2007. View at Publisher · View at Google Scholar · View at Scopus
  44. E. Rådestad, H. Wikell, M. Engström et al., “Alpha/beta T-cell depleted grafts as an immunological booster to treat graft failure after hematopoietic stem cell transplantation with HLA-matched related and unrelated donors,” Journal of Immunology Research, vol. 2014, Article ID 578741, 14 pages, 2014. View at Publisher · View at Google Scholar · View at Scopus
  45. M. Bonneville, R. L. O'Brien, and W. K. Born, “γδ T cell effector functions: a blend of innate programming and acquired plasticity,” Nature Reviews Immunology, vol. 10, no. 7, pp. 467–478, 2010. View at Publisher · View at Google Scholar
  46. S. Chiplunkar, S. Dhar, D. Wesch, and D. Kabelitz, “γδ T cells in cancer immunotherapy: current status and future prospects,” Immunotherapy, vol. 1, no. 4, pp. 663–678, 2009. View at Publisher · View at Google Scholar · View at Scopus
  47. K. T. Godder, P. J. Henslee-Downey, J. Mehta et al., “Long term disease-free survival in acute leukemia patients recovering with increased γδ T cells after partially mismatched related donor bone marrow transplantation,” Bone Marrow Transplantation, vol. 39, no. 12, pp. 751–757, 2007. View at Publisher · View at Google Scholar · View at Scopus
  48. J. L. M. Ferrara and P. Reddy, “Pathophysiology of graft-versus-host disease,” Seminars in Hematology, vol. 43, no. 1, pp. 3–10, 2006. View at Publisher · View at Google Scholar
  49. A. Q. Gomes, D. S. Martins, and B. Silva-Santos, “Targeting γδ T lymphocytes for cancer immunotherapy: from novel mechanistic insight to clinical application,” Cancer Research, vol. 70, no. 24, pp. 10024–10027, 2010. View at Publisher · View at Google Scholar · View at Scopus
  50. W. Scheper, S. Van Dorp, S. Kersting et al., “γδ T cells elicited by CMV reactivation after allo-SCT cross-recognize CMV and leukemia,” Leukemia, vol. 27, no. 6, pp. 1328–1338, 2013. View at Publisher · View at Google Scholar · View at Scopus
  51. D. Balashov, A. Shcherbina, M. Maschan et al., “Single-center experience of unrelated and haploidentical stem cell transplantation with TCRαβ and CD19 depletion in children with primary immunodeficiency syndromes,” Biology of Blood and Marrow Transplantation, vol. 21, no. 11, pp. 1955–1962, 2015. View at Publisher · View at Google Scholar
  52. C. Anasetti, D. Amos, P. G. Beatty et al., “Effect of HLA compatibility on engraftment of bone marrow transplants in patients with leukemia or lymphoma,” The New England Journal of Medicine, vol. 320, no. 4, pp. 197–204, 1989. View at Publisher · View at Google Scholar · View at Scopus
  53. P. G. Beatty, R. A. Clift, E. M. Mickelson et al., “Marrow transplantation from related donors other than HLA-identical siblings,” The New England Journal of Medicine, vol. 313, no. 13, pp. 765–771, 1985. View at Publisher · View at Google Scholar · View at Scopus
  54. “The host barrier in animal models of T-cell depleted allogeneic bone marrow transplantation. T-cell depletion in allogeneic bone marrow transplantation,” in Serono Symposia Review, Y. Reisner, T. Lapidot, T. S. Singer, and E. Schwartz, Eds., 1988.
  55. P. J. Martin, “The role of donor lymphoid cells in allogeneic marrow engraftment,” Bone Marrow Transplantation, vol. 6, no. 5, pp. 283–289, 1990. View at Google Scholar · View at Scopus
  56. R. J. Soiffer, P. Mauch, N. J. Tarbell et al., “Total lymphoid irradiation to prevent graft rejection in recipients of HLA non-identical T cell-depleted allogeneic marrow,” Bone Marrow Transplantation, vol. 7, no. 1, pp. 23–33, 1991. View at Google Scholar · View at Scopus
  57. F. Aversa, A. Tabilio, A. Velardi et al., “Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched hla haplotype,” The New England Journal of Medicine, vol. 339, no. 17, pp. 1186–1193, 1998. View at Publisher · View at Google Scholar · View at Scopus
  58. E. Bachar-Lustig, N. Rachamim, H.-W. Li, F. Lan, and Y. Reisner, “Megadose of T cell-depleted bone marrow overcomes MHC barriers in sublethally irradiated mice,” Nature Medicine, vol. 1, no. 12, pp. 1268–1273, 1995. View at Publisher · View at Google Scholar · View at Scopus
  59. F. Aversa, A. Tabilio, A. Terenzi et al., “Successful engraftment of T-cell-depleted haploidentical ‘three-loci’ incompatible transplants in leukemia patients by addition of recombinant human granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells to bone marrow inoculum,” Blood, vol. 84, no. 11, pp. 3948–3955, 1994. View at Google Scholar · View at Scopus
  60. Y. Reisner and M. F. Martelli, “Bone marrow transplantation across HLA barriers by increasing the number of transplanted cells,” Immunology Today, vol. 16, no. 9, pp. 437–440, 1995. View at Publisher · View at Google Scholar · View at Scopus
  61. E. Naparstek, M. Delukina, R. Or et al., “Engraftment of marrow allografts treated with Campath-1 monoclonal antibodies,” Experimental Hematology, vol. 27, no. 7, pp. 1210–1218, 1999. View at Publisher · View at Google Scholar · View at Scopus
  62. J. L. M. Ferrara, R. Levy, and N. J. Chao, “Pathophysiologic mechanisms of acute graft-vs.-host disease,” Biology of Blood and Marrow Transplantation, vol. 5, no. 6, pp. 347–356, 1999. View at Publisher · View at Google Scholar · View at Scopus
  63. N. A. Kernan, G. Bartsch, R. C. Ash et al., “Analysis of 462 transplantations from unrelated donors facilitated by the national marrow donor program,” The New England Journal of Medicine, vol. 328, no. 9, pp. 593–602, 1993. View at Publisher · View at Google Scholar · View at Scopus
  64. L. Luznik, P. V. O'Donnell, H. J. Symons et al., “HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide,” Biology of Blood and Marrow Transplantation, vol. 14, no. 6, pp. 641–650, 2008. View at Publisher · View at Google Scholar · View at Scopus
  65. H. Ogawa, K. Ikegame, S. Yoshihara et al., “Unmanipulated HLA 2-3 antigen-mismatched (haploidentical) stem cell transplantation using nonmyeloablative conditioning,” Biology of Blood and Marrow Transplantation, vol. 12, no. 10, pp. 1073–1084, 2006. View at Publisher · View at Google Scholar · View at Scopus
  66. S. Kreiter, N. Winkelmann, P. M. Schneider et al., “Failure of sustained engraftment after non-myeloablative conditioning with low-dose TBI and T cell-reduced allogeneic peripheral stem cell transplantation,” Bone Marrow Transplantation, vol. 28, no. 2, pp. 157–161, 2001. View at Publisher · View at Google Scholar · View at Scopus
  67. J. R. Passweg, S. Meyer-Monard, M. Gregor et al., “Non-myeloablative stem cell transplantation: high stem cell dose will not compensate for T cell depletion in allogeneic non-myeloablative stem cell transplantation,” Bone Marrow Transplantation, vol. 30, no. 5, pp. 267–271, 2002. View at Publisher · View at Google Scholar · View at Scopus
  68. D. A. Rizzieri, L. P. Koh, G. D. Long et al., “Partially matched, nonmyeloablative allogeneic transplantation: clinical outcomes and immune reconstitution,” Journal of Clinical Oncology, vol. 25, no. 6, pp. 690–697, 2007. View at Publisher · View at Google Scholar · View at Scopus
  69. P. V. O'Donnell, L. Luznik, R. J. Jones et al., “Nonmyeloablative bone marrow transplantation from partially HLA-mismatched related donors using posttransplantation cyclophosphamide,” Biology of Blood and Marrow Transplantation, vol. 8, no. 7, pp. 377–386, 2002. View at Publisher · View at Google Scholar · View at Scopus
  70. H. Mayumi, K. Himeno, N. Tokuda, and K. Nomoto, “Drug-induced tolerance to allografts in mice. VII. Optimal protocol and mechanism of cyclophosphamide-induced tolerance in an H-2 haplotype-identical strain combination,” Transplantation Proceedings, vol. 18, no. 2, pp. 363–369, 1986. View at Google Scholar · View at Scopus
  71. H. Mayumi, M. Umesue, and K. Nomoto, “Cyclophosphamide-induced immunological tolerance: an overview,” Immunobiology, vol. 195, no. 2, pp. 129–139, 1996. View at Publisher · View at Google Scholar · View at Scopus
  72. L. Luznik, S. Jalla, L. W. Engstrom, R. Lannone, and E. J. Fuchs, “Durable engraftment of major histocompatibility complex-incompatible cells after nonmyeloablative conditioning with fludarabine, low-dose total body irradiation, and posttransplantation cyclophosphamide,” Blood, vol. 98, no. 12, pp. 3456–3464, 2001. View at Publisher · View at Google Scholar · View at Scopus
  73. L. Luznik, L. W. Engstrom, R. Iannone, and E. J. Fuchs, “Posttransplantation cyclophosphamide facilitates engraftment of major histocompatibility complex-identical allogeneic marrow in mice conditioned with low-dose total body irradiation,” Biology of Blood and Marrow Transplantation, vol. 8, no. 3, pp. 131–138, 2002. View at Publisher · View at Google Scholar · View at Scopus
  74. R. J. Jones, J. P. Barber, M. S. Vala et al., “Assessment of aldehyde dehydrogenase in viable cells,” Blood, vol. 85, no. 10, pp. 2742–2746, 1995. View at Google Scholar · View at Scopus
  75. S. Sakaguchi, N. Sakaguchi, M. Asano, M. Itoh, and M. Toda, “Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor α-chains (CD25): breakdown of a single mechanism of self-tolerance causes various autoimmune diseases,” The Journal of Immunology, vol. 155, no. 3, pp. 1151–1164, 1995. View at Google Scholar · View at Scopus
  76. Z. Fehérvari and S. Sakaguchi, “CD4+ Tregs and immune control,” The Journal of Clinical Investigation, vol. 114, no. 9, pp. 1209–1217, 2004. View at Publisher · View at Google Scholar · View at Scopus
  77. C. I. Kingsley, M. Karim, A. R. Bushell, and K. J. Wood, “CD25+CD4+ regulatory T cells prevent graft rejection: CTLA-4- and IL-10-dependent immunoregulation of alloresponses,” The Journal of Immunology, vol. 168, no. 3, pp. 1080–1086, 2002. View at Publisher · View at Google Scholar · View at Scopus
  78. J. Yu, X. Ren, F. Yan et al., “Alloreactive natural killer cells promote haploidentical hematopoietic stem cell transplantation by expansion of recipient-derived CD4+CD25+ regulatory T cells,” Transplant International, vol. 24, no. 2, pp. 201–212, 2011. View at Publisher · View at Google Scholar · View at Scopus
  79. M. Edinger, P. Hoffmann, J. Ermann et al., “CD4+CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation,” Nature Medicine, vol. 9, no. 9, pp. 1144–1150, 2003. View at Publisher · View at Google Scholar · View at Scopus
  80. A. Trenado, F. Charlotte, S. Fisson et al., “Recipient-type specific CD4+CD25+ regulatory T cells favor immune reconstitution and control graft-versus-host disease while maintaining graft-versus-leukemia,” The Journal of Clinical Investigation, vol. 112, no. 11, pp. 1688–1696, 2003. View at Publisher · View at Google Scholar · View at Scopus
  81. S. C. Jones, G. F. Murphy, and R. Korngold, “Post-hematopoietic cell transplantation control of graft-versus-host disease by donor CD4+25+ T cells to allow an effective graft-versus-leukemia response,” Biology of Blood and Marrow Transplantation, vol. 9, no. 4, pp. 243–256, 2003. View at Publisher · View at Google Scholar · View at Scopus
  82. K. Rezvani, S. Mielke, M. Ahmadzadeh et al., “High donor FOXP3-positive regulatory T-cell (Treg) content is associated with a low risk of GVHD following HLA-matched allogeneic SCT,” Blood, vol. 108, no. 4, pp. 1291–1297, 2006. View at Publisher · View at Google Scholar · View at Scopus
  83. V. H. Nguyen, S. Shashidhar, D. S. Chang et al., “The impact of regulatory T cells on T-cell immunity following hematopoietic cell transplantation,” Blood, vol. 111, no. 2, pp. 945–953, 2008. View at Publisher · View at Google Scholar · View at Scopus
  84. M. Di Ianni, F. Falzetti, A. Carotti et al., “Immunoselection and clinical use of T regulatory cells in HLA-haploidentical stem cell transplantation,” Best Practice & Research: Clinical Haematology, vol. 24, no. 3, pp. 459–466, 2011. View at Publisher · View at Google Scholar · View at Scopus
  85. A. M. Hanash and R. B. Levy, “Donor CD4+CD25+ T cells promote engraftment and tolerance following MHC-mismatched hematopoietic cell transplantation,” Blood, vol. 105, no. 4, pp. 1828–1836, 2005. View at Publisher · View at Google Scholar · View at Scopus
  86. P. Hoffmann and M. Edinger, “CD4+CD25+ regulatory T cells and graft-versus-host disease,” Seminars in Hematology, vol. 43, no. 1, pp. 62–69, 2006. View at Publisher · View at Google Scholar · View at Scopus
  87. M. Di Ianni, F. Falzetti, A. Carotti et al., “Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation,” Blood, vol. 117, no. 14, pp. 3921–3928, 2011. View at Publisher · View at Google Scholar · View at Scopus
  88. M. Di Ianni, B. Del Papa, D. Cecchini et al., “Immunomagnetic isolation of CD4+CD25+FoxP3+ natural T regulatory lymphocytes for clinical applications,” Clinical & Experimental Immunology, vol. 156, no. 2, pp. 246–253, 2009. View at Publisher · View at Google Scholar · View at Scopus
  89. L. M. Williams and A. Y. Rudensky, “Maintenance of the Foxp3-dependent developmental program in mature regulatory T cells requires continued expression of Foxp3,” Nature Immunology, vol. 8, no. 3, pp. 277–284, 2007. View at Publisher · View at Google Scholar · View at Scopus
  90. D. J. Hartigan-O'Connor, C. Poon, E. Sinclair, and J. M. McCune, “Human CD4+ regulatory T cells express lower levels of the IL-7 receptor alpha chain (CD127), allowing consistent identification and sorting of live cells,” Journal of Immunological Methods, vol. 319, no. 1-2, pp. 41–52, 2007. View at Publisher · View at Google Scholar · View at Scopus
  91. M. Battaglia, A. Stabilini, B. Migliavacca, J. Horejs-Hoeck, T. Kaupper, and M.-G. Roncarolo, “Rapamycin promotes expansion of functional CD4+CD25+FOXP3+ regulatory T cells of both healthy subjects and type 1 diabetic patients,” The Journal of Immunology, vol. 177, no. 12, pp. 8338–8347, 2006. View at Publisher · View at Google Scholar · View at Scopus
  92. J. Peccatori, A. Forcina, D. Clerici et al., “Sirolimus-based graft-versus-host disease prophylaxis promotes the in vivo expansion of regulatory T cells and permits peripheral blood stem cell transplantation from haploidentical donors,” Leukemia, vol. 29, no. 2, pp. 396–405, 2014. View at Publisher · View at Google Scholar
  93. C. Anasetti, B. R. Logan, S. J. Lee et al., “Peripheral-blood stem cells versus bone marrow from unrelated donors,” The New England Journal of Medicine, vol. 367, no. 16, pp. 1487–1496, 2012. View at Publisher · View at Google Scholar · View at Scopus
  94. O. Ringdén, M. Labopin, D. W. Beelen et al., “Bone marrow or peripheral blood stem cell transplantation from unrelated donors in adult patients with acute myeloid leukaemia, an Acute Leukaemia Working Party analysis in 2262 patients,” Journal of Internal Medicine, vol. 272, no. 5, pp. 472–483, 2012. View at Publisher · View at Google Scholar · View at Scopus
  95. A. M. Raiola, A. Dominietto, A. Ghiso et al., “Unmanipulated haploidentical bone marrow transplantation and posttransplantation cyclophosphamide for hematologic malignancies after myeloablative conditioning,” Biology of Blood and Marrow Transplantation, vol. 19, no. 1, pp. 117–122, 2013. View at Publisher · View at Google Scholar · View at Scopus
  96. P. D. Bartolomeo, S. Santarone, G. De Angelis et al., “Haploidentical, unmanipulated, G-CSF-primed bone marrow transplantation for patients with high-risk hematologic malignancies,” Blood, vol. 121, no. 5, pp. 849–857, 2013. View at Publisher · View at Google Scholar · View at Scopus
  97. C. G. Kanakry, S. Ganguly, M. Zahurak et al., “Aldehyde dehydrogenase expression drives human regulatory T cell resistance to posttransplantation cyclophosphamide,” Science Translational Medicine, vol. 5, no. 211, Article ID 211ra157, 2013. View at Publisher · View at Google Scholar · View at Scopus