Main Article Content

Franco Aversa
Lucia Prezioso
Ilenia Manfra
Federica Galaverna
Angelica Spolzino
Alessandro Monti


stem cell transplantation, haploidentical, posttransplant immune recovery, lymphocyte recovery, infections,


The advantage of using a Human Leukocyte Antigen (HLA)-mismatched related donor is that almost every patient who does not have a HLA-identical donor or who urgently needs hematopoietic stem cell transplantation (HSCT) has at least one family member with whom shares one haplotype (haploidentical) and who is promptly available as a donor. The major challenge of haplo-HSCT is intense bi-directional alloreactivity leading to high incidences of graft rejection and graft-versus-host disease (GVHD). Advances in graft processing and in pharmacologic prophylaxis of GVHD have reduced these risks and have made haplo-HSCT a viable alternative for patients lacking a matched donor. Indeed, the haplo-HSCT  has spread to centers worldwide even though some centers have preferred an approach based on T cell depletion of G-CSF-mobilized peripheral blood progenitor cells (PBPCs), others have focused on new strategies for GvHD prevention, such as G-CSF priming of bone marrow and robust post-transplant immune suppression or post-transplant cyclophosphamide (PTCY). Today, the graft can be a megadose of T-cell depleted PBPCs or standard dose of unmanipulated bone marrow and/or PBPCs.  Although haplo-HSCT modalities are based mainly on high intensity conditioning regimens, recently introduced reduced intensity regimens (RIC)   showed promise in decreasing early transplant-related mortality (TRM), and extending the opportunity of HSCT to an elderly population with more comorbidities. Infections are still mostly responsible for toxicity and non-relapse mortality due to prolonged immunosuppression related, or not, to GVHD. Future challenges lie in determining the safest preparative conditioning regimen, minimizing GvHD and promoting rapid and more robust immune reconstitution.


Download data is not yet available.

Abstract 3535
PDF Downloads 767
HTML Downloads 1267


1. Gragert L, Eapen M, Williams E, Freeman J, Spellman S, Baitty R, Hartzman R, Rizzo JD, Horowitz M, Confer D, Maiers M. HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry. N Engl J Med. 2014;371(4):339-48.
2. Kanakry CG, de Lima MJ, and Luznik L. Alternative donor allogeneic hematopoietic cell transplantation for acute myeloid leukemia. Sem in Hematol, 2015; 52 (3):232–42.
3. Fabricius WA, Ramanathan M. Review on Haploidentical Hematopoietic Cell Transplantation in Patients with Hematologic Malignancies. Adv Hematol. 2016;2016:5726132. doi: 10.1155/2016/5726132. Epub 2016 Feb 29.
4. Reisner Y, Hagin D, Martelli MF. Haploidentical hematopoietic transplantation: current status and future perspectives. Blood. 2011;118(23):6006-17.
5. Bayraktar UD, Champlin RE, Ciurea SO. Progress in haploidentical stem cell transplantation. Biol Blood Marrow Transplant. 2012;18(3):372-80
6. Aversa F, Martelli MM, Reisner Y. Use of stem cells from mismatched related donors. Curr Opin Hematol. 1997;4(6):419-22.
7. Kang Y, Chao NJ, Aversa F. Unmanipulated or CD34 selected haplotype mismatched transplants. Curr Opin Hematol. 2008;15(6):561-7.
8. Aversa F, Tabilio A, Terenzi A, Velardi A, Falzetti F, Giannoni C, Iacucci R, Zei T, Martelli MP, Gambelunghe C, Rossetti M, Caputo P, Latini P, Aristei C, Raymondi C, Reisner Y and Martelli MF. 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. 1994;84(11):3948-55.
9. Aversa F, Tabilio A, Velardi A, Cunningham I, Terenzi A, Falzetti F, Ruggeri L, Barbabietola G, Aristei C, Latini P, Reisner Y, Martelli MF. 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(17):1186-93.
10. Al Malki MM, Horowitz M, Handgretinger R, Leung W, Roy DC, Huang XJ, Fuchs E, Locatelli F, Blaise D, Mineishi S, Martelli M, Miller J, June C, Ai HS, Luznik L, Mavilio D, Lugli E, van den Brink MR, Champlin RE, Ciurea SO. Proceedings from the Second Haploidentical Stem Cell Transplantation Symposium-Haplo2014, San Francisco, California, December 4, 2014. Biol Blood Marrow Transplant. 2016;22(4):594-604
11. Luznik L, O'Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M, Gooley TA, Piantadosi S, Kaup M, Ambinder RF, Huff CA, Matsui W, Bolaños-Meade J, Borrello I, Powell JD, Harrington E, Warnock S, Flowers M, Brodsky RA, Sandmaier BM, Storb RF, Jones RJ, Fuchs EJ. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008;14(6):641-50.
12. Bacigalupo A, Sica S. HLA Haplotype Mismatch Transplants and Posttransplant Cyclophosphamide. Adv Hematol. 2016;2016:7802967. doi: 10.1155/2016/7802967. Epub 2016 Apr 7. Review
13. Aversa F, Martelli MF, Velardi A. Haploidentical hematopoietic stem cell transplantation with a megadose T-cell-depleted graft: harnessing natural and adaptive immunity. Semin Oncol. 2012;39(6):643-52.
14. Storek J, Dawson MA, Maloney DG. Correlation between the numbers of naive T cells infused with blood stem cell allografts and the counts of naive T cells after transplantation, Biol. Blood Marrow Transplant. 2003; 9: 781–4.
15. Mackall CL, Bare CV, Granger LA, Sharrow SO, Titus JA, Gress RE. Thymic-independent T cell regeneration occurs via antigen-driven expansion of peripheral T cells resulting in a repertoire that is limited in diversity and prone to skewing, J. Immunol. 1996; 156: 4609–16.
16. Arstila TP, Casrouge A, Baron V, Even J, Kanellopoulos J, Kourilsky P. A direct estimate of the human alphabeta T cell receptor diversity, Science 1999;286:958–61.
17. Sairafi D, Mattsson J, Uhlin M, Uzunel M. Thymic function after allogeneic stem cell transplantation is dependent on graft source and predictive of long term survival. Clin Immunol. 2012;142(3):343-50.
18. Waller EK, Langston AA, Lonial S, Cherry J, Somani J, Allen AJ, Rosenthal H, Redei I. Pharmacokinetics and pharmacodynamics of anti-thymocyte globulin in recipients of partially HLA-matched blood hematopoietic progenitor cell transplantation. Biol Blood Marrow Transplant. 2003;9(7):460-71.
19. Weinberg K, Blazar BR, Wagner JE, Agura E, Hill BJ, Smogorzewska M, Koup RA, Betts MR, Collins RH, Douek DC: Factors affecting thymic function after allogeneic hematopoietic stem cell transplantation. Blood 2001, 97:1458-1466.
20. Raiola AM, Dominietto A, di Grazia C, Lamparelli T, Gualandi F, Ibatici A, Bregante S, Van Lint MT, Varaldo R, Ghiso A, Gobbi M, Carella AM, Signori A, Galaverna F, Bacigalupo A. Unmanipulated haploidentical transplants compared with other alternative donors and matched sibling grafts. Biol Blood Marrow Transplant. 2014;20(10):1573-9.
21. Ciurea SO, Zhang MJ, Bacigalupo AA, Bashey A, Appelbaum FR, Aljitawi OS, Armand P, Antin JH, Chen J, Devine SM, Fowler DH, Luznik L, Nakamura R, O’Donnell PO, Perales MA, Pingali SR, Porter DL, Riches MR, Ringdén O, Rocha V, Vij R, Weisdorf DJ, Champlin RE, Horowitz MM, Fuchs EJ, Eapen M. “Haploidentical transplant with posttransplant cyclophosphamide vs matched unrelated donor transplant for acute myeloid leukemia. Blood, 2015; 126 (8):1033–40.
22. Yu Wang, Qi-Fa Liu, Lan-Ping Xu, Kai-Yan Liu, Xiao-Hui Zhang, Xiao Ma, Zhi-Ping Fan, De-Pei Wu, Xiao-Jun Huang. Haploidentical vs identical sibling transplant for AML in remission: a multicenter, prospective study. Blood, 2015; vol. 125 (25): 3956–62.
23. Balletto E, Mikulska M. Bacterial Infections in Hematopoietic Stem Cell Transplant Recipients. Mediterr J Hematol Infect Dis. 2015;7(1):e2015045. doi: 10.4084/MJHID.2015.045.
24. Chung H, Pamp SJ, Hill JA, Surana NK, Edelman SM, Troy EB, Reading NC, Villablanca EJ, Wang S, Mora JR, Umesaki Y, Mathis D, Benoist C, Relman DA, Kasper DL. Gut immune maturation depends on colonization with a host-specific microbiota. Cell. 2012;149:1578–93.
25. Wang W, Xu S, Ren Z, Jiang J, Zheng S. Gut microbiota and allogeneic transplantation. J Transl Med. 2015;13:275. doi: 10.1186/s12967-015-0640-8. Review.
26. Chung H, Kasper DL. Microbiota-stimulated immune mechanisms to maintain gut homeostasis. Curr Opin Immunol 2010; 22 (4): 455–60.
27. Murphy S, Nguyen VH. Role of gut microbiota in graft-versus-host disease. Leukemia Lymphoma 2011; 52 (10): 1844–56.
28. Aroniadis OC, Brandt LJ. Intestinal microbiota and the efficacy of fecal microbiota transplantation in gastrointestinal disease. Gastroenterol Hepatol 2014; 10 (4): 230–37.
29. Taur Y, Xavier JB, Lipuma L, Ubeda C, Goldberg J, Gobourne A, Lee YJ, Dubin KA, Socci ND, Viale A, Perales MA, Jenq RR, van den Brink MR, Pamer EG. Intestinal domination and the risk of bacteremia in patients undergoing allogeneic hematopoietic stem cell transplantation. Clin Infect Dis. 2012;55:905–14.
30. Jenq RR, Ubeda C, Taur Y, Menezes CC, Khanin R, Dudakov JA, Liu C, West ML, Singer NV, Equinda MJ, Gobourne A, Lipuma L, Young LF, Smith OM, Ghosh A, Hanash AM, Goldberg JD, Aoyama K, Blazar BR, Pamer EG, van den Brink MR. Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation. J Exp Med. 2012;209:903–11.
31. Holler E, Butzhammer P, Schmid K, Hundsrucker C, Koestler J, Peter K, Zhu W, Sporrer D, Hehlgans T, Kreutz M, Holler B, Wolff D, Edinger M, Andreesen R, Levine JE, Ferrara JL, Gessner A, Spang R, Oefner P. Metagenomic analysis of the stool microbiome in patients receiving allogeneic stem cell transplantation: loss of diversity is associated with use of systemic antibiotics and more pronounced in gastrointestinal graft-versus-host disease. Biology of Blood and Marrow Transplantation. 2014;20:640–5.
32. Girmenia C1, Ferretti A, Barberi W. Epidemiology and risk factors for invasive fungal diseases in hematopoietic stem cell transplantation. Curr Opin Hematol. 2014;21(6):459-65.
33. Girmenia C, Raiola AM, Piciocchi A, Algarotti A, Stanzani M, Cudillo L, Pecoraro C, Guidi S, Iori AP, Montante B, Chiusolo P, Lanino E, Carella AM, Zucchetti E, Bruno B, Irrera G, Patriarca F, Baronciani D, Musso M, Prete A, Risitano AM, Russo D, Mordini N, Pastore D, Vacca A, Onida F, Falcioni S, Pisapia G, Milone G, Vallisa D, Olivieri A, Bonini A, Castagnola E, Sica S, Majolino I, Bosi A, Busca A, Arcese W, Bandini G, Bacigalupo A, Rambaldi A, Locasciulli A. Incidence and outcome of invasive fungal diseases after allogeneic stem cell transplantation: a prospective study of the Gruppo Italiano Trapianto Midollo Osseo (GITMO). Biol Blood Marrow Transplant. 2014;20(6):872-80.
34. Kontoyiannis DP, Marr KA, Park BJ, Alexander BD, Anaissie EJ, Walsh TJ, Ito J, Andes DR, Baddley JW, Brown JM, Brumble LM, Freifeld AG, Hadley S, Herwaldt LA, Kauffman CA, Knapp K, Lyon GM, Morrison VA, Papanicolaou G, Patterson TF, Perl TM, Schuster MG, Walker R, Wannemuehler KA, Wingard JR, Chiller TM, Pappas PG. Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001–2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clin Infect Dis 2010; 50:1091–1100.
35. Sun Y, Meng F, Han M, Zhang X, Yu L, Huang H, Wu D, Ren H, Wang C, Shen Z, Ji Y, Huang X. Epidemiology, management, and outcome of invasive fungal disease in patients undergoing hematopoietic stem cell transplantation in China: a multicenter prospective observational study. Biol Blood Marrow Transplant. 2015;21(6):1117-26.
36. Di Bartolomeo P, Santarone S, De Angelis G, Picardi A, Cudillo L, Cerretti R, Adorno G, Angelini S, Andreani M, De Felice L, Rapanotti MC, Sarmati L, Bavaro P, Papalinetti G, Di Nicola M, Papola F, Montanari M, Nagler A, Arcese W. Haploidentical, unmanipulated, G-CSF-primed bone marrow transplantation for patients with high-risk hematologic malignancies. Blood. 2013;121(5):849-57.
37. Raiola AM, Dominietto A, Ghiso A, Di Grazia C, Lamparelli T, Gualandi F, Bregante S, Van Lint MT, Geroldi S, Luchetti S, Ballerini F, Miglino M, Varaldo R, Bacigalupo A. Unmanipulated haploidentical bone marrow transplantation and posttransplantation cyclophosphamide for hematologic malignancies after myeloablative conditioning. Biol Blood Marrow Transplant 2013; 19:117–122.
38. Crocchiolo R, Bramanti S, Vai A, Sarina B, Mineri R, Casari E, Tordato F, Mauro E, Timofeeva I, Lugli E, Mavilio D, Carlo-Stella C, Santoro A, Castagna L. Infections after T-replete haploidentical transplantation and high-dose cyclophosphamide as graft-versus-host disease prophylaxis. Transpl Infect Dis. 2015;17(2):242-9.
39. Raiola A, Dominietto A, Varaldo R, Ghiso A, Galaverna F, Bramanti S, Todisco E, Sarina B, Giordano L, Ibatici A, Santoro A, Clavio M, Bacigalupo A, Castagna L. Unmanipulated haploidentical BMT following nonmyeloablative conditioning and posttransplantation CY for advanced Hodgkin’s lymphoma. Bone Marrow Transplant 2014; 49:190–4.
40. Ljungman P, Perez-Bercoff L, Jonsson J, Avetisyan G, Sparrelid E, Aschan J, Barkholt L, Larsson K, Winiarski J, Yun Z, Ringdén O. Risk factors for the development of cytomegalovirus disease after allogeneic stem cell transplantation. Haematologica. 2006;91(1):78-83.
41. Hebart H, Einsele H. Clinical aspects of CMV infection after stem cell transplantation. Hum Immunol. 2004;65(5):432-6.
42. Loren AW, Porter DL, Stadtmauer EA, Tsai DE. Posttransplant lymphoproliferative disorder: a review. Bone Marrow Translpant. 2003;31:145–55.
43. de la Cámara R. CMV in Hematopoietic Stem Cell Transplantation. Mediterr J Hematol Infect Dis. 2016 Jun 20;8(1):e2016031. doi: 10.4084/MJHID.2016.031. eCollection 2016. Review
44. Broers AE, van Der Holt R, van Esser JW, Gratama JW, Henzen-Logmans S, Kuenen-Boumeester V, Löwenberg B, Cornelissen JJ. Increased transplantrelated morbidity and mortality in CMV- seropositive patients despite highly effective prevention of CMV disease after allogeneic T-celldepleted stem cell transplantation. Blood 2000; 95:2240–5.
45. Ljungman P, Brand R, Hoek J, de la Camara R, Cordonnier C, Einsele H, Styczynski J, Ward KN, Cesaro S; Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation. Donor Cytomegalovirus Status Influences the Outcome of Allogeneic Stem Cell Transplant: A Study by the European Group for Blood and Marrow Transplantation. Clinical Infectious Diseases. 2014;59(4):473-81.
46. Ljungman P, Einsele H, Frassoni F, Niederwieser D, Cordonnier C. Donor CMV serological status influences the outcome of CMV seropositive recipients after unrelated donor stem cell transplantation: an EBMT Megafile analysis. Blood 2003; 102:4255–60.
47. Howard DS, Phillips II GL, Reece DE, Munn RK, Henslee-Downey J, Pittard M, Barker M, Pomeroy C. Adenovirus infections in hematopoietic stem cell transplant recipients. Clin Infect Dis 1999;29:1494–1501.
48. Taniguchi K, Yoshihara S, Tamaki H, Fujimoto T, Ikegame K, Kaida K, Nakata J, Inoue T, Kato R, Fujioka T, Okada M, Soma T, Ogawa H. Incidence and treatment strategy for disseminated adenovirus disease after haploidentical stem cell transplantation. Ann Hematol. 2012;91(8):1305-12
49. Robin M1, Marque-Juillet S, Scieux C, Peffault de Latour R, Ferry C, Rocha V, Molina JM, Bergeron A, Devergie A, Gluckman E, Ribaud P, Socié G. Disseminated adenovirus infections after allogeneic hematopoietic stem cell transplantation: incidence, risk factors and outcome. Haematologica. 2007;92(9):1254-7.
50. Munoz-Cobo B, Solano C, Nieto J, de la Cámara R, Remigia MJ, Garcia-Noblejas A, López J, Benet I, Hernández-Boluda JC, Costa E, Bravo D, Navarro D. Surveillance for adenovirus DNAemia early after transplantation in adult recipients of unrelated-donor allogeneic stem cell transplants in the absence of clinically suspected infection. Bone Marrow Transplant 2011;46:1484–6.
51. Hubmann M, Fritsch S, Zoellner AK, Prevalsek D, Engel N, Bücklein V, Mumm F, Schulz C, Stemmler HJ, Jäger G, Ledderose G, Kolb HJ, Hausmann A, Hiddemann W, Moosmann A, Tischer J. Occurrence, risk factors and outcome of adenovirus infection in adult recipients of allogeneic hematopoietic stem cell transplantation. J Clin Virol. 2016;82:33-40.
52. Ruggeri A, Roth-Guepin G, Battipaglia G, Mamez AC, Malard F, Gomez A, Brissot E, Belhocine R, Vekhoff A, Lapusan S, Isnard F, Legrand O, Gozlan J, Boutolleau D, Ledraa T, Labopin M, Rubio MT, Mohty M. Incidence and risk factors for hemorrhagic cystitis in unmanipulated haploidentical transplant recipients Transpl Infect Dis. 2015;17(6):822-30.
53. Ogata M1, Satou T, Kadota J, Saito N, Yoshida T, Okumura H, Ueki T, Nagafuji K, Kako S, Uoshima N, Tsudo M, Itamura H, Fukuda T. Human herpesvirus 6 (HHV-6) reactivation and HHV-6 encephalitis after allogeneic hematopoietic cell transplantation: a multicenter, prospective study. Clin Infect Dis. 2013;57(5):671-81.
54. Sahin U, Toprak KS, Atilla PA, Atilla E, Demirer T. An overview of infectious complications after allogeneic hematopoietic stem cell transplantation. J Infect Chemother, 2016; 22: 505-14.
55. Cavattoni I, Ayuk F, Zabelina T, Bacher A, Cayroglu E, Knospe V, Illies T, Aepfelbacher M, Richard G, Kröger N, Bacher U. Diagnosis of Toxoplasma gondii infection after allogeneic stem cell transplantation can be difficult and requires intensive scrutiny. Leuk Lymphoma 2010;51:1530–5.
56. Derouin F, Pelloux H; ESCMID Study Group on Clinical Parasitology. Prevention of toxoplasmosis in transplant patients. Clin Microbiol Infect 2008;14:1089–1101.
57. Martino R, Bretagne S, Einsele H, Maertens J, Ullmann AJ, Parody R, Schumacher U, Pautas C, Theunissen K, Schindel C, Muñoz C, Margall N, Cordonnier C; Infectious Disease Working Party of the European Group for Blood and Marrow Transplantation. Early detection of Toxoplasma infection by molecular monitoring of Toxoplasma gondii in peripheral blood samples after allogeneic stem cell transplantation. Clin Infect Dis 2005;40:67–78.
58. Aversa F, Terenzi A, Tabilio A, Falzetti F, Carotti A, Ballanti S, Felicini R, Falcinelli F, Velardi A, Ruggeri L, Aloisi T, Saab JP, Santucci A, Perruccio K, Martelli MP, Mecucci C, Reisner Y, Martelli MF. 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(15):3447-54.
59. Marek A, Stern M, Chalandon Y, Ansari M, Ozsahin H, Güngör T, Gerber B, Kühne T, Passweg JR, Gratwohl A, Tichelli A, Seger R, Schanz U, Halter J, Stussi G; Swiss Blood Stem Cell Transplantation. The impact of T-cell depletion techniques on the outcome after haploidentical hematopoietic SCT. Bone Marrow Transplant. 2014;49(1):55-61.
60. Schmidt-Hieber M1, Schwarck S, Stroux A, Ganepola S, Reinke P, Thiel E, Uharek L, Blau IW. Immune reconstitution and cytomegalovirus infection after allogeneic stem cell transplantation: the important impact of in vivo T cell depletion. Int J Hematol. 2010;91(5):877-85.
61. Perruccio K, Tosti A, Burchielli E, Topini F, Ruggeri L, Carotti A, Capanni M, Urbani E, Mancusi A, Aversa F, Martelli MF, Romani L, Velardi A. Transferring functional immune responses to pathogens after haploidentical hematopoietic transplantation. Blood. 2005;106(13):4397-406.
62. Chen BJ, Cui X, Liu C, Chao NJ. Prevention of graft-versus-host disease while preserving graft-versus-leukemia effect after selective depletion of host-reactive T cells by photodynamic cell purging. Blood 2002;99(9):3083–8.
63. Perruccio K, Topini F, Tosti A, Carotti A, Burchielli E, Ruggeri L, Mancusi A, Urbani E, Aversa F, Martelli MF, Velardi A. Optimizing a photoallodepletion protocol for adoptive immunotherapy after haploidentical SCT. Bone Marrow Transplant. 2012;47(9):1196-200.
64. Bastien J-P, Roy J, Roy DC. Selective T-cell depletion for haplotype-mismatched allogeneic stem cell transplantation. Semin Oncol 2012;39(6):674–82.
65. Bonini C, Grez M, Traversari C, Ciceri F, Marktel S, Ferrari G, Dinauer M, Sadat M, Aiuti A, Deola S, Radrizzani M, Hagenbeek A, Apperley J, Ebeling S, Martens A, Kolb HJ, Weber M, Lotti F, Grande A, Weissinger E, Bueren JA, Lamana M, Falkenburg JH, Heemskerk MH, Austin T, Kornblau S, Marini F, Benati C, Magnani Z, Cazzaniga S, Toma S, Gallo-Stampino C, Introna M, Slavin S, Greenberg PD, Bregni M, Mavilio F, Bordignon C. Safety of retroviral gene marking with a truncated NGF receptor. Nat Med. 2003;9(4):367-9
66. Marktel S, Magnani Z, Ciceri F, Cazzaniga S, Riddell SR, Traversari C, Bordignon C, Bonini C. Immunologic potential of donor lymphocytes expressing a suicide gene for early immune reconstitution after hematopoietic T-cell-depleted stem cell transplantation. Blood. 2003;101:1290–8.
67. Ciceri F, Bonini C, Gallo-Stampino C, Bordignon C. Modulation of GvHD by suicide-gene transduced donor T lymphocytes: clinical applications in mismatched transplantation. Cytotherapy. 2005;7:144–9
68. Ciceri F, Bonini C, Stanghellini MT, Bondanza A, Traversari C, Salomoni M, Turchetto L, Colombi S, Bernardi M, Peccatori J, Pescarollo A, Servida P, Magnani Z, Perna SK, Valtolina V, Crippa F, Callegaro L, Spoldi E, Crocchiolo R, Fleischhauer K, Ponzoni M, Vago L, Rossini S, Santoro A, Todisco E, Apperley J, Olavarria E, Slavin S, Weissinger EM, Ganser A, Stadler M, Yannaki E, Fassas A, Anagnostopoulos A, Bregni M, Stampino CG, Bruzzi P, Bordignon C. Infusion of suicide-gene-engineered donor lymphocytes after family haploidentical haemopoietic stem-cell transplantation for leukaemia (the TK007 trial): a non-randomised phase I-II study. Lancet Oncol. 2000;10(5):489-500.
69. Di Stasi A, Tey SK, Dotti G, Fujita Y, Kennedy-Nasser A, Martinez C, Straathof K, Liu E, Durett AG, Grilley B, Liu H, Cruz CR, Savoldo B, Gee AP, Schindler J, Krance RA, Heslop HE, Spencer DM, Rooney CM, Brenner MK. Inducible apoptosis as a safety switch for adoptive cell therapy. N Engl J Med. 2011;365:1673–83.
70. Zhou X, Dotti G, Krance RA, Martinez CA, Naik S, Kamble RT, Durett AG, Dakhova O, Savoldo B, Di Stasi A, Spencer DM, Lin YF, Liu H, Grilley BJ, Gee AP, Rooney CM, Heslop HE, Brenner MK. Inducible caspase-9 suicide gene controls adverse effects from alloreplete T cells after haploidentical stem cell transplantation. Blood. 2015;125:4103-4113.
71. Di Ianni M, Del Papa B, Cecchini D, Bonifacio E, Moretti L, Zei T, Ostini RI, Falzetti F, Fontana L, Tagliapietra G, Maldini C, Martelli MF, Tabilio A. Immunomagnetic isolation of CD4+CD25+FoxP3+ natural T regulatory lymphocytes for clinical applications. Clin Exp Immunol. 2009;156(2):246-53
72. Di Ianni M, Falzetti F, Carotti A, Terenzi A, Castellino F, Bonifacio E, Del Papa B, Zei T, Ostini RI, Cecchini D, Aloisi T, Perruccio K, Ruggeri L, Balucani C, Pierini A, Sportoletti P, Aristei C, Falini B, Reisner Y, Velardi A, Aversa F, Martelli MF. Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation. Blood. 2011;117(14):3921-8.
73. Martelli MF, Di Ianni M, Ruggeri L, Falzetti F, Carotti A, Terenzi A, Pierini A, Massei MS, Amico L, Urbani E, Del Papa B, Zei T, Iacucci Ostini R, Cecchini D, Tognellini R, Reisner Y, Aversa F, Falini B, Velardi A. HLA-haploidentical transplantation with regulatory and conventional T-cell adoptive immunotherapy prevents acute leukemia relapse. Blood. 2014;124(4):638-44.
74. Li Pira G, Di Cecca S, Montanari M, Moretta L, Manca F. Specific removal of alloreactive T-cells to prevent GvHD in hemopoietic stem cell transplantation: rationale, strategies and perspectives. Blood Rev. 2016 Jul;30(4):297-307
75. Handgretinger R. New approaches to graft engineering for haploidentical bone marrow transplantation. Semin Oncol 2012;39(6):664–73.
76. Lang P, Feuchtinger T, Teltschik HM, Schwinger W, Schlegel P, Pfeiffer M, Schumm M, Lang AM, Lang B, Schwarze CP, Ebinger M, Urban C, Handgretinger R. Improved immune recovery after transplantation of TCR??/CD19-depleted allografts from haploidentical donors in pediatric patients. Bone Marrow Transplant. 2015;50 Suppl 2:S6-10.
77. Airoldi I, Bertaina A, Prigione I, Zorzoli A, Pagliara D, Cocco C, Meazza R, Loiacono F, Lucarelli B, Bernardo ME, Barbarito G, Pende D, Moretta A, Pistoia V, Moretta L, Locatelli F. ?? T-cell reconstitution after HLA-haploidentical hematopoietic transplantation depleted of TCR-??+/CD19+ lymphocytes. Blood. 2015;125(15):2349-58.
78. Li Pira G, Malaspina D, Girolami E, Biagini S, Cicchetti E, Conflitti G, Broglia M, Ceccarelli S, Lazzaro S, Pagliara D, Meschini A, Bertaina A, Montanari M, Locatelli F. Selective Depletion of ?? T Cells and B Cells for HLA-Haploidentical Hematopoietic Stem Cell Transplantation. a Three-Year Follow-Up of Procedure Efficiency. Biol Blood Marrow Transplant. 2016 Aug 9. pii: S1083-8791(16)30281-6. doi:
79. Pfeffer K, Schoel B, Gulle H, Kaufmann SH, Wagner H. Primary responses of human T cells to mycobacteria: a frequent set of gamma/delta T cells are stimulated by protease-resistant ligands. Eur J Immunol. 1990;20(5):1175-9.
80. Ciofani M, Zúñiga-Pflücker JC. Determining ?? versus ?ß T cell development. Nat Rev Immunol. 2010;10(9):657-63
81. Groh V, Steinle A, Bauer S, Spies T. Recognition of stress-induced MHC molecules by intestinal epithelial gammadelta T cells. Science. 1998;279(5357):1737-40
82. Bertaina A, Merli P, Rutella S, Pagliara D, Bernardo ME, Masetti R, Pende D, Falco M, Handgretinger R, Moretta F, Lucarelli B, Brescia LP, Li Pira G, Testi M, Cancrini C, Kabbara N, Carsetti R, Finocchi A, Moretta A, Moretta L, Locatelli F. HLA-haploidentical stem cell transplantation after removal of ??+ T and B cells in children with nonmalignant disorders. Blood. 2014;124(5):822-6.
83. Perko R, Kang G, Sunkara A, Leung W, Thomas PG, Dallas MH. Gamma delta T cell reconstitution is associated with fewer infections and improved event-free survival after hematopoietic stem cell transplantation for pediatric leukemia. Biol Blood Marrow Transplant. 2015;21(1):130-6.
84. Prezioso L, Bonomini S, Sammarelli G, Schifano C, Rossetti E, Monti A, Todaro G, Craviotto L, Manfra I, Spolzino A, Cambò B, Sassi M, Caramatti C, Aversa F . Haploidentical stem cell transplantation after negative depletion of T cells expressing the ?? chain of the T-cell receptor (TCR) for adults with hematological malignancies. EBMT Annual Meeting, 2013. Blood 2013; 122: 4609 (abstract).
85. Huang XJ, Liu DH, Liu KY, Xu LP, Chen H, Han W, Chen YH, Wang JZ, Gao ZY, Zhang YC, Jiang Q, Shi HX, Lu DP. Haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion for the treatment of hematological malignancies. Bone Marrow Transplant. 2006;38(4):291-7.
86. Chang YJ, Huang XJ. Haploidentical bone marrow transplantation without T-cell depletion. Semin Oncol. 2012;39(6):653-63
87. Huang XJ, Liu DH, Liu KY, Xu LP, Chen H, Han W, Chen YH, Zhang XH, Lu DP. Treatment of acute leukemia with unmanipulated HLA-mismatched/haploidentical blood and bone marrow transplantation. Biol Blood Marrow Transplant. 2009;15(2):257-65
88. Liu J, Xu LP, Bian Z, Chang YJ, Wang Y, Zhang XH, Huang XJ. Differential impact of two doses of antithymocyte globulin conditioning on lymphocyte recovery upon haploidentical hematopoietic stem cell transplantation. J Transl Med. 2015;13:391.
89. Arcese W, Picardi A, Santarone S, De Angelis G, Cerretti R, Cudillo L, Pennese E, Bavaro P, Olioso P, Dentamaro T, Cupelli L, Chierichini A, Ferrari A, Mengarelli A, Tirindelli MC, Testi M, Di Piazza F, Di Bartolomeo P; Rome Transplant Network. Haploidentical, G-CSF-primed, unmanipulated bone marrow transplantation for patients with high-risk hematological malignancies: an update. Bone Marrow Transplant. 2015;50 Suppl 2:S24-30.
90. Mayumi H, Umesue M, Nomoto K. Cyclophosphamide-induced immunological tolerance: an overview. Immunobiology. 1996;195:129-139.
91. Robinson TM, O'Donnell PV, Fuchs EJ, Luznik L. Haploidentical bone marrow and stem cell transplantation: experience with post-transplantation cyclophosphamide. Semin Hematol. 2016;53(2):90-7.
92. Ciurea SO1, Mulanovich V, Saliba RM, Bayraktar UD, Jiang Y, Bassett R, Wang SA, Konopleva M, Fernandez-Vina M, Montes N, Bosque D, Chen J, Rondon G, Alatrash G, Alousi A, Bashir Q, Korbling M, Qazilbash M, Parmar S, Shpall E, Nieto Y, Hosing C, Kebriaei P, Khouri I, Popat U, de Lima M, Champlin RE. Improved early outcomes using a T cell replete graft compared with T cell depleted haploidentical hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2012;18(12):1835-44.
93. Tischer J, Engel N, Fritsch S, Prevalsek D, Hubmann M, Schulz C, Zoellner AK, Bücklein V, Reibke R, Mumm F, Rieger CT, Hill W, Ledderose G, Stemmler HJ, Köhnke T, Jäger G, Kolb HJ, Schmid C, Moosmann A, Hausmann A. Virus infection in HLA-haploidentical hematopoietic stem cell transplantation: incidence in the context of immune recovery in two different transplantation settings. Ann Hematol. 2015;94(10):1677-88.