Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Contemporary haploidentical stem cell transplant strategies in children with hematological malignancies

Abstract

The barriers to HLA-mismatched or haploidentical hematopoietic stem cell transplantation (HSCT), namely GvHD and graft failure, have been overcome with novel transplant platforms. Post-transplant Cyclophosphamide (PTCy) is widely available, feasible and easy to implement. TCRαβ T and B cell depletion comes with consistent GvHD preventive benefits irrespective of age and indication. Naive T-cell depletion helps prevention of severe viral reactivations. The Beijing protocol shows promising outcomes in patients with poor remission status at the time of transplantation. For children, the toxicities and late outcomes related to these transplants are truly relevant as they suffer the most in the long run from transplant-related toxicities, especially chronic GvHD. While comparing the outcomes of different Haplo-HSCT approaches, one must understand the transplant immunobiology and factors affecting the transplant outcomes. Leukemia remission status at the time of conditioning is a consistent factor affecting the transplant outcomes using any of these platforms. Prospective comparison of these platforms lacks in a homogenous population; however, the evidence is growing, and this review highlights the areas of research gaps.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: T-cell replete Haplo-HSCT and factors affecting its outcomes.

Similar content being viewed by others

References

  1. Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002;295:2097–2100. https://doi.org/10.1126/science.1068440

    Article  CAS  PubMed  Google Scholar 

  2. Aversa F, Terenzi A, Tabilio A, Falzetti F, Carotti A, Ballanti S, 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;23:3447–54. https://doi.org/10.1200/JCO.2005.09.117

    Article  PubMed  Google Scholar 

  3. Handgretinger R, Klingebiel T, Lang P, Schumm M, Neu S, Geiselhart A, et al. Megadose transplantation of purified peripheral blood CD34(+) progenitor cells from HLA-mismatched parental donors in children. Bone Marrow Transpl. 2001;27:777–83. https://doi.org/10.1038/sj.bmt.1702996

    Article  CAS  Google Scholar 

  4. Elmariah H, Kasamon YL, Zahurak M, Macfarlane KW, Tucker N, Rosner GL, et al. Haploidentical bone marrow transplantation with post-transplant cyclophosphamide using non-first-degree related donors. Biol Blood Marrow Transpl. 2018;24:1099–102. https://doi.org/10.1016/j.bbmt.2018.02.005

    Article  Google Scholar 

  5. Shah RM, Elfeky R, Nademi Z, Qasim W, Amrolia P, Chiesa R, et al. T-cell receptor alphabeta(+) and CD19(+) cell-depleted haploidentical and mismatched hematopoietic stem cell transplantation in primary immune deficiency. J Allergy Clin Immunol. 2018;141:1417–26 e1411. https://doi.org/10.1016/j.jaci.2017.07.008

    Article  CAS  PubMed  Google Scholar 

  6. Uygun V, Karasu G, Daloglu H, Ozturkmen S, Caki Kilic S, Hazar V, et al. Haploidentical hematopoietic stem cell transplantation with post-transplant high-dose cyclophosphamide in high-risk children: a single-center study. Pediatr Transpl. 2019;23:e13546. https://doi.org/10.1111/petr.13546

    Article  CAS  Google Scholar 

  7. Ciurea SO, Al Malki MM, Kongtim P, Fuchs EJ, Luznik L, Huang XJ, et al. The European Society for Blood and Marrow Transplantation (EBMT) consensus recommendations for donor selection in haploidentical hematopoietic cell transplantation. Bone Marrow Transpl. 2020;55:12–24. https://doi.org/10.1038/s41409-019-0499-z

    Article  CAS  Google Scholar 

  8. Wang Y, Chang YJ, Xu LP, Liu KY, Liu DH, Zhang XH, et al. Who is the best donor for a related HLA haplotype-mismatched transplant? Blood. 2014;124:843–50. https://doi.org/10.1182/blood-2014-03-563130

    Article  CAS  PubMed  Google Scholar 

  9. Emadi A, Jones RJ, Brodsky RA. Cyclophosphamide and cancer: golden anniversary. Nat Rev Clin Oncol. 2009;6:638–47. https://doi.org/10.1038/nrclinonc.2009.146

    Article  CAS  PubMed  Google Scholar 

  10. Luznik L, O’Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transpl. 2008;14:641–50. https://doi.org/10.1016/j.bbmt.2008.03.005

    Article  CAS  Google Scholar 

  11. Luznik L, Jones RJ, Fuchs EJ. High-dose cyclophosphamide for graft-versus-host disease prevention. Curr Opin Hematol. 2010;17:493–9. https://doi.org/10.1097/MOH.0b013e32833eaf1b

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kanakry CG, Ganguly S, Zahurak M, Bolanos-Meade J, Thoburn C, Perkins B, et al. Aldehyde dehydrogenase expression drives human regulatory T cell resistance to posttransplantation cyclophosphamide. Sci Transl Med. 2013;5:211ra157 https://doi.org/10.1126/scitranslmed.3006960

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ganguly S, Ross DB, Panoskaltsis-Mortari A, Kanakry CG, Blazar BR, Levy RB, et al. Donor CD4+ Foxp3+ regulatory T cells are necessary for posttransplantation cyclophosphamide-mediated protection against GVHD in mice. Blood. 2014;124:2131–41. https://doi.org/10.1182/blood-2013-10-525873

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Russo A, Oliveira G, Berglund S, Greco R, Gambacorta V, Cieri N, et al. NK cell recovery after haploidentical HSCT with posttransplant cyclophosphamide: dynamics and clinical implications. Blood. 2018;131:247–62. https://doi.org/10.1182/blood-2017-05-780668

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Jones RJ, Barber JP, Vala MS, Collector MI, Kaufmann SH, Ludeman SM, et al. Assessment of aldehyde dehydrogenase in viable cells. Blood. 1995;85:2742–6.

    Article  CAS  Google Scholar 

  16. 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. Transpl Proc. 1986;18:363–9.

    CAS  Google Scholar 

  17. O’Donnell PV, Luznik L, Jones RJ, Vogelsang GB, Leffell MS, Phelps M, et al. Nonmyeloablative bone marrow transplantation from partially HLA-mismatched related donors using posttransplantation cyclophosphamide. Biol Blood Marrow Transpl. 2002;8:377–86.

    Article  Google Scholar 

  18. Nomoto K, Eto M, Yanaga K, Nishimura Y, Maeda T, Nomoto K. Interference with cyclophosphamide-induced skin allograft tolerance by cyclosporin A. J Immunol. 1992;149:2668–74.

    CAS  PubMed  Google Scholar 

  19. Raiola AM, Dominietto A, Ghiso A, Di Grazia C, Lamparelli T, Gualandi F, et al. Unmanipulated haploidentical bone marrow transplantation and posttransplantation cyclophosphamide for hematologic malignancies after myeloablative conditioning. Biol Blood Marrow Transpl. 2013;19:117–22. https://doi.org/10.1016/j.bbmt.2012.08.014

    Article  CAS  Google Scholar 

  20. Chiusolo P, Bug G, Olivieri A, Brune M, Mordini N, Alessandrino PE, et al. A modified post-transplant cyclophosphamide regimen, for unmanipulated haploidentical marrow transplantation, in acute myeloid leukemia: a multicenter study. Biol Blood Marrow Transpl. 2018;24:1243–9. https://doi.org/10.1016/j.bbmt.2018.01.031

    Article  CAS  Google Scholar 

  21. Ruggeri A, Labopin M, Battipaglia G, Chiusolo P, Tischer J, Diez-Martin JL, et al. Timing of Post-Transplantation Cyclophosphamide Administration in Haploidentical Transplantation: A Comparative Study on Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Biol Blood Marrow Transpl. 2020;26:1915–22. https://doi.org/10.1016/j.bbmt.2020.06.026

    Article  CAS  Google Scholar 

  22. Bacigalupo A, Dominietto A, Ghiso A, Di Grazia C, Lamparelli T, Gualandi F, et al. Unmanipulated haploidentical bone marrow transplantation and post-transplant cyclophosphamide for hematologic malignanices following a myeloablative conditioning: an update. Bone Marrow Transpl. 2015;50:S37–39. https://doi.org/10.1038/bmt.2015.93

    Article  CAS  Google Scholar 

  23. Medina D, Estacio M, Rosales M, Manzi E. Haploidentical stem cell transplant with post-transplantation cyclophosphamide and mini-dose methotrexate in children. Hematol Oncol Stem Cell Ther. 2020;13:208–13. https://doi.org/10.1016/j.hemonc.2020.01.003

    Article  CAS  PubMed  Google Scholar 

  24. Bradstock KF, Bilmon I, Kwan J, Micklethwaite K, Blyth E, Deren S, et al. Single-Agent High-Dose Cyclophosphamide for Graft-versus-Host Disease Prophylaxis in Human Leukocyte Antigen-Matched Reduced-Intensity Peripheral Blood Stem Cell Transplantation Results in an Unacceptably High Rate of Severe Acute Graft-versus-Host Disease. Biol Blood Marrow Transpl. 2015;21:941–4. https://doi.org/10.1016/j.bbmt.2015.01.020

    Article  CAS  Google Scholar 

  25. Chaleff S, Otto M, Barfield RC, Leimig T, Iyengar R, Martin J, et al. A large-scale method for the selective depletion of alphabeta T lymphocytes from PBSC for allogeneic transplantation. Cytotherapy. 2007;9:746–54. https://doi.org/10.1080/14653240701644000

    Article  CAS  PubMed  Google Scholar 

  26. Locatelli F, Merli P, Rutella S. At the Bedside: Innate immunity as an immunotherapy tool for hematological malignancies. J Leukoc Biol. 2013;94:1141–57. https://doi.org/10.1189/jlb.0613343

    Article  CAS  PubMed  Google Scholar 

  27. Ruggeri L, Mancusi A, Capanni M, Urbani E, Carotti A, Aloisi T, et al. Donor natural killer cell allorecognition of missing self in haploidentical hematopoietic transplantation for acute myeloid leukemia: challenging its predictive value. Blood. 2007;110:433–40. https://doi.org/10.1182/blood-2006-07-038687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Vantourout P, Hayday A. Six-of-the-best: unique contributions of gammadelta T cells to immunology. Nat Rev Immunol. 2013;13:88–100. https://doi.org/10.1038/nri3384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol. 2008;8:726–36. https://doi.org/10.1038/nri2395

    Article  CAS  PubMed  Google Scholar 

  30. Arai S, Sahaf B, Narasimhan B, Chen GL, Jones CD, Lowsky R, et al. Prophylactic rituximab after allogeneic transplantation decreases B-cell alloimmunity with low chronic GVHD incidence. Blood. 2012;119:6145–54. https://doi.org/10.1182/blood-2011-12-395970

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Gaziev J, Isgro A, Sodani P, Paciaroni K, De Angelis G, Marziali M, et al. Haploidentical HSCT for hemoglobinopathies: improved outcomes with TCRalphabeta(+)/CD19(+)-depleted grafts. Blood Adv. 2018;2:263–70. https://doi.org/10.1182/bloodadvances.2017012005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Di Stasi A, Tey SK, Dotti G, Fujita Y, Kennedy-Nasser A, Martinez C, et al. Inducible apoptosis as a safety switch for adoptive cell therapy. N. Engl J Med. 2011;365:1673–83. https://doi.org/10.1056/NEJMoa1106152

    Article  PubMed  PubMed Central  Google Scholar 

  33. Galaverna F, Ruggeri A, Merli P, Kapoor N, Agarwal-Hashmi R, Aquino V, et al. Administration of BPX-501 Cells Following Ab T and B-Cell-Depleted HLA Haploidentical HSCT (Haplo-HSCT) in Children with Acute Leukemias (AL). ASBMT, 2019. Biol Blood Marrow Transpl. 2019;25:S15.

    Article  Google Scholar 

  34. Anderson BE, McNiff J, Yan J, Doyle H, Mamula M, Shlomchik MJ, et al. Memory CD4+ T cells do not induce graft-versus-host disease. J Clin Investig. 2003;112:101–8. https://doi.org/10.1172/JCI17601

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zheng H, Matte-Martone C, Jain D, McNiff J, Shlomchik WD. Central memory CD8+ T cells induce graft-versus-host disease and mediate graft-versus-leukemia. J Immunol. 2009;182:5938–48. https://doi.org/10.4049/jimmunol.0802212

    Article  CAS  PubMed  Google Scholar 

  36. Chen BJ, Deoliveira D, Cui X, Le NT, Son J, Whitesides JF, et al. Inability of memory T cells to induce graft-versus-host disease is a result of an abortive alloresponse. Blood. 2007;109:3115–23. https://doi.org/10.1182/blood-2006-04-016410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Bleakley M, Otterud BE, Richardt JL, Mollerup AD, Hudecek M, Nishida T, et al. Leukemia-associated minor histocompatibility antigen discovery using T-cell clones isolated by in vitro stimulation of naive CD8+ T cells. Blood. 2010;115:4923–33. https://doi.org/10.1182/blood-2009-12-260539

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Bleakley M, Heimfeld S, Jones LA, Turtle C, Krause D, Riddell SR, et al. Engineering human peripheral blood stem cell grafts that are depleted of naive T cells and retain functional pathogen-specific memory T cells. Biol Blood Marrow Transpl. 2014;20:705–16. https://doi.org/10.1016/j.bbmt.2014.01.032

    Article  CAS  Google Scholar 

  39. Appay V, van Lier RA, Sallusto F, Roederer M. Phenotype and function of human T lymphocyte subsets: consensus and issues. Cytom A. 2008;73:975–83. https://doi.org/10.1002/cyto.a.20643

    Article  Google Scholar 

  40. Chang YJ, Zhao XY, Huang XJ. Granulocyte colony-stimulating factor-primed unmanipulated haploidentical blood and marrow transplantation. Front Immunol. 2019;10:2516 https://doi.org/10.3389/fimmu.2019.02516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Huang XJ, Liu DH, Liu KY, Xu LP, Chen H, Han W, et al. Treatment of acute leukemia with unmanipulated HLA-mismatched/haploidentical blood and bone marrow transplantation. Biol Blood Marrow Transpl. 2009;15:257–65. https://doi.org/10.1016/j.bbmt.2008.11.025

    Article  CAS  Google Scholar 

  42. Luo XH, Chang YJ, Xu LP, Liu DH, Liu KY, Huang XJ. The impact of graft composition on clinical outcomes in unmanipulated HLA-mismatched/haploidentical hematopoietic SCT. Bone Marrow Transpl. 2009;43:29–36. https://doi.org/10.1038/bmt.2008.267

    Article  CAS  Google Scholar 

  43. Zhao XY, Chang YJ, Xu LP, Liu DH, Liu KY, Huang XJ. Association of natural killer cells in allografts with transplant outcomes in patients receiving G-CSF-mobilized PBSC grafts and G-CSF-primed BM grafts from HLA-haploidentical donors. Bone Marrow Transpl. 2009;44:721–8. https://doi.org/10.1038/bmt.2009.73

    Article  Google Scholar 

  44. Chang YJ, Xu LP, Wang Y, Zhang XH, Chen H, Chen YH, et al. Controlled, randomized, open-label trial of risk-stratified corticosteroid prevention of acute graft-versus-host disease after haploidentical transplantation. J Clin Oncol. 2016;34:1855–63. https://doi.org/10.1200/JCO.2015.63.8817

    Article  CAS  PubMed  Google Scholar 

  45. Yan CH, Liu DH, Liu KY, Xu LP, Liu YR, Chen H, et al. Risk stratification-directed donor lymphocyte infusion could reduce relapse of standard-risk acute leukemia patients after allogeneic hematopoietic stem cell transplantation. Blood. 2012;119:3256–62. https://doi.org/10.1182/blood-2011-09-380386

    Article  CAS  PubMed  Google Scholar 

  46. Chang YJ, Luznik L, Fuchs EJ, Huang XJ. How do we choose the best donor for T-cell-replete, HLA-haploidentical transplantation? J Hematol Oncol. 2016;9:35 https://doi.org/10.1186/s13045-016-0265-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Di Bartolomeo P, Santarone S, De Angelis G, Picardi A, Cudillo L, Cerretti R, et al. Haploidentical, unmanipulated, G-CSF-primed bone marrow transplantation for patients with high-risk hematologic malignancies. Blood. 2013;121:849–57. https://doi.org/10.1182/blood-2012-08-453399

    Article  CAS  PubMed  Google Scholar 

  48. Imus PH, Blackford AL, Bettinotti M, Luznik L, Fuchs EJ, Huff CA, et al. Severe cytokine release syndrome after haploidentical peripheral blood transplantation. Biol Blood Marrow Transpl. 2019;25:2431–7. https://doi.org/10.1016/j.bbmt.2019.07.027

    Article  CAS  Google Scholar 

  49. Mariotti J, Taurino D, Marino F, Bramanti S, Sarina B, Morabito L, et al. Pretransplant active disease status and HLA class II mismatching are associated with increased incidence and severity of cytokine release syndrome after haploidentical transplantation with posttransplant cyclophosphamide. Cancer Med. 2020;9:52–61. https://doi.org/10.1002/cam4.2607

    Article  CAS  PubMed  Google Scholar 

  50. Hong KT, Kang HJ, Choi JY, Hong CR, Cheon JE, Park JD, et al. Favorable outcome of post-transplantation cyclophosphamide haploidentical peripheral blood stem cell transplantation with targeted busulfan-based myeloablative conditioning using intensive pharmacokinetic monitoring in pediatric patients. Biol Blood Marrow Transpl. 2018;24:2239–44. https://doi.org/10.1016/j.bbmt.2018.06.034

    Article  CAS  Google Scholar 

  51. Jaiswal SR, Chakrabarti A, Chatterjee S, Bhargava S, Ray K, O’Donnell P, et al. Haploidentical peripheral blood stem cell transplantation with post-transplantation cyclophosphamide in children with advanced acute leukemia with fludarabine-, busulfan-, and melphalan-based conditioning. Biol Blood Marrow Transpl. 2016;22:499–504. https://doi.org/10.1016/j.bbmt.2015.11.010

    Article  CAS  Google Scholar 

  52. Klein OR, Chen AR, Gamper C, Loeb D, Zambidis E, Llosa N, et al. Alternative-donor hematopoietic stem cell transplantation with post-transplantation cyclophosphamide for nonmalignant disorders. Biol Blood Marrow Transpl. 2016;22:895–901. https://doi.org/10.1016/j.bbmt.2016.02.001

    Article  CAS  Google Scholar 

  53. Bonfim C, Ribeiro L, Nichele S, Loth G, Bitencourt M, Koliski A, et al. Haploidentical bone marrow transplantation with post-transplant cyclophosphamide for children and adolescents with fanconi anemia. Biol Blood Marrow Transpl. 2017;23:310–7. https://doi.org/10.1016/j.bbmt.2016.11.006

    Article  Google Scholar 

  54. Ruggeri A, Roth-Guepin G, Battipaglia G, Mamez AC, Malard F, Gomez A, et al. Incidence and risk factors for hemorrhagic cystitis in unmanipulated haploidentical transplant recipients. Transpl Infect Dis. 2015;17:822–30. https://doi.org/10.1111/tid.12455

    Article  CAS  PubMed  Google Scholar 

  55. Symons HJ, Zahurak M, Cao Y, Chen A, Cooke K, Gamper C, et al. Myeloablative haploidentical BMT with posttransplant cyclophosphamide for hematologic malignancies in children and adults. Blood Adv. 2020;4:3913–25. https://doi.org/10.1182/bloodadvances.2020001648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Kersun LS, Wimmer RS, Hoot AC, Meadows AT. Secondary malignant neoplasms of the bladder after cyclophosphamide treatment for childhood acute lymphocytic leukemia. Pediatr Blood Cancer. 2004;42:289–91. https://doi.org/10.1002/pbc.10451

    Article  PubMed  Google Scholar 

  57. Katewa S, Kharya G, Karnik L, Kassim AA, de la Fuente J. Pre-transplantation suppression of haemopoiesis is associated with a high rate of macrophage activation syndrome in Ptcy haploidentical transplantation for haemoglobinopathies. Blood. 2017;130:1931–1931.

    Google Scholar 

  58. Jaiswal SR, Chakrabarti A, Chatterjee S, Bhargava S, Ray K, Chakrabarti S. Hemophagocytic syndrome following haploidentical peripheral blood stem cell transplantation with post-transplant cyclophosphamide. Int J Hematol. 2016;103:234–42. https://doi.org/10.1007/s12185-015-1905-y

    Article  CAS  PubMed  Google Scholar 

  59. Haastrup E, Ifversen MRS, Heilmann C, Fischer-Nielsen A. Depletion of alphabeta+ T and B cells using the CliniMACS prodigy: results of 10 graft-processing procedures from haploidentical donors. Transfus Med Hemother. 2019;46:446–9. https://doi.org/10.1159/000497074

    Article  PubMed  PubMed Central  Google Scholar 

  60. Bertaina A, Zecca M, Buldini B, Sacchi N, Algeri M, Saglio F, et al. Unrelated donor vs HLA-haploidentical alpha/beta T-cell and B-cell depleted HSCT in children with acute leukemia. Blood. 2018;132:2594–607. https://doi.org/10.1182/blood-2018-07-861575

    Article  CAS  PubMed  Google Scholar 

  61. Elfeky R, Shah RM, Unni MNM, Ottaviano G, Rao K, Chiesa R, et al. New graft manipulation strategies improve the outcome of mismatched stem cell transplantation in children with primary immunodeficiencies. J Allergy Clin Immunol. 2019;144:280–93. https://doi.org/10.1016/j.jaci.2019.01.030

    Article  PubMed  Google Scholar 

  62. Balashov D, Shcherbina A, Maschan M, Trakhtman P, Skvortsova Y, Shelikhova L, et al. Single-center experience of unrelated and haploidentical stem cell transplantation with TCRalphabeta and CD19 depletion in children with primary immunodeficiency syndromes. Biol Blood Marrow Transpl. 2015;21:1955–62. https://doi.org/10.1016/j.bbmt.2015.07.008

    Article  Google Scholar 

  63. Sawada A, Shimizu M, Isaka K, Higuchi K, Mayumi A, Yoshimoto Y, et al. Feasibility of HLA-haploidentical hematopoietic stem cell transplantation with post-transplantation cyclophosphamide for advanced pediatric malignancies. Pediatr Hematol Oncol. 2014;31:754–64. https://doi.org/10.3109/08880018.2014.961214

    Article  CAS  PubMed  Google Scholar 

  64. Klein OR, Buddenbaum J, Tucker N, Chen AR, Gamper CJ, Loeb D, et al. Nonmyeloablative haploidentical bone marrow transplantation with post-transplantation cyclophosphamide for pediatric and young adult patients with high-risk hematologic malignancies. Biol Blood Marrow Transpl. 2017;23:325–32. https://doi.org/10.1016/j.bbmt.2016.11.016

    Article  Google Scholar 

  65. Dufort G, Castillo L, Pisano S, Castiglioni M, Carolina P, Andrea I, et al. Haploidentical hematopoietic stem cell transplantation in children with high-risk hematologic malignancies: outcomes with two different strategies for GvHD prevention. Ex vivo T-cell depletion and post-transplant cyclophosphamide: 10 years of experience at a single center. Bone Marrow Transpl. 2016;51:1354–60. https://doi.org/10.1038/bmt.2016.161

    Article  CAS  Google Scholar 

  66. Solomon SR, Sizemore CA, Sanacore M, Zhang X, Brown S, Holland HK, et al. Total Body Irradiation-Based Myeloablative Haploidentical Stem Cell Transplantation Is a Safe and Effective Alternative to Unrelated Donor Transplantation in Patients Without Matched Sibling Donors. Biol Blood Marrow Transpl. 2015;21:1299–307. https://doi.org/10.1016/j.bbmt.2015.03.003

    Article  Google Scholar 

  67. Katsanis E, Sapp LN, Reid SC, Reddivalla N, Stea B. T-cell replete myeloablative haploidentical bone marrow transplantation is an effective option for pediatric and young adult patients with high-risk hematologic malignancies. Front Pediatr. 2020;8:282 https://doi.org/10.3389/fped.2020.00282

    Article  PubMed  PubMed Central  Google Scholar 

  68. Katsanis E, Sapp LN, Varner N, Koza S, Stea B, Zeng Y. Haploidentical bone marrow transplantation with post-transplant cyclophosphamide/bendamustine in pediatric and young adult patients with hematologic malignancies. Biol Blood Marrow Transpl. 2018;24:2034–9. https://doi.org/10.1016/j.bbmt.2018.06.007

    Article  CAS  Google Scholar 

  69. Lopez-Hernandez G, Lopez-Santiago N, Olaya-Vargas A, Pérez-García M, Ramírez-Uribe RMN, Salazar-Rosales HdP, et al. Haploidentical stem cell transplantation with post-transplant cyclophosphamide as graft-versus-host disease prophylaxis in pediatric hematologic malignancies. Blood. 2018;132:5705–5705. https://doi.org/10.1182/blood-2018-99-115083

    Article  Google Scholar 

  70. Berger M, Lanino E, Cesaro S, Zecca M, Vassallo E, Faraci M, et al. Feasibility and outcome of haploidentical hematopoietic stem cell transplantation with post-transplant high-dose cyclophosphamide for children and adolescents with hematologic malignancies: an AIEOP-GITMO retrospective multicenter study. Biol Blood Marrow Transpl. 2016;22:902–9. https://doi.org/10.1016/j.bbmt.2016.02.002

    Article  CAS  Google Scholar 

  71. Satwani P, Jin Z, Duffy D, Morris E, Bhatia M, Garvin JH, et al. Transplantation-related mortality, graft failure, and survival after reduced-toxicity conditioning and allogeneic hematopoietic stem cell transplantation in 100 consecutive pediatric recipients. Biol Blood Marrow Transpl. 2013;19:552–61. https://doi.org/10.1016/j.bbmt.2012.12.005

    Article  Google Scholar 

  72. Lang P, Feuchtinger T, Teltschik HM, Schwinger W, Schlegel P, Pfeiffer M, et al. Improved immune recovery after transplantation of TCRalphabeta/CD19-depleted allografts from haploidentical donors in pediatric patients. Bone Marrow Transpl. 2015;50:S6–10. https://doi.org/10.1038/bmt.2015.87

    Article  CAS  Google Scholar 

  73. Lang PJ, Schlegel PG, Meisel R, Schulz AS, Greil J, Bader P, et al. Safety and efficacy of Tcralpha/Beta and CD19 depleted haploidentical stem cell transplantation following reduced intensity conditioning in children: results of a prospective multicenter phase I/II clinical trial. Blood. 2017;130:214–214.

    Article  Google Scholar 

  74. Shelikhova L, Ilushina M, Shekhovtsova Z, Shasheleva D, Khismatullina R, Kurnikova E, et al. Alphabeta T cell-depleted haploidentical hematopoietic stem cell transplantation without antithymocyte globulin in children with chemorefractory acute myelogenous leukemia. Biol Blood Marrow Transpl. 2019;25:e179–e182. https://doi.org/10.1016/j.bbmt.2019.01.023

    Article  Google Scholar 

  75. Jacoby E, Varda-Bloom N, Goldstein G, Hutt D, Churi C, Vernitsky H et al. Comparison of two cytoreductive regimens for alphabeta-T-cell-depleted haploidentical HSCT in pediatric malignancies: Improved engraftment and outcome with TBI-based regimen. Pediatr Blood Cancer. 2018;65. https://doi.org/10.1002/pbc.26839

  76. Bielorai B, Jacoby E, Varda-Bloom N, Hutt D, Churi C, Vernitsky H, et al. Haploidentical hematopoietic stem cell transplantation with alphabetaTCR+/CD19+ depletion in pediatric patients with malignant and non-malignant disorders. Bone Marrow Transpl. 2019;54:694–7. https://doi.org/10.1038/s41409-019-0607-0

    Article  CAS  Google Scholar 

  77. Locatelli F, Merli P, Pagliara D, Li Pira G, Falco M, Pende D, et al. Outcome of children with acute leukemia given HLA-haploidentical HSCT after alphabeta T-cell and B-cell depletion. Blood. 2017;130:677–85. https://doi.org/10.1182/blood-2017-04-779769

    Article  CAS  PubMed  Google Scholar 

  78. Merli P, Algeri M, Li Pira G, Falco M, Pende D, Bertaina V, et al. Alpha/beta T-cell and B-cell depletion HLA-haploidentical hematopoietic stem cell transplantation is an effective treatment for children/young adults with acute leukemia. Blood. 2018;132:2169–2169. https://doi.org/10.1182/blood-2018-99-117136

    Article  Google Scholar 

  79. Shelikhova L, Shekhovtsova Z, Balashov D, Boyakova E, Muzalevskyi I, Gutovskaya E, et al. Tcrαβ+/CD19+-depletion in hematopoietic stem cells transplantation from matched unrelated and haploidentical donors following treosulfan or TBI-based conditioning in pediatric acute lymphoblastic leukemia patients. Blood. 2016;128:4672–4672.

    Article  Google Scholar 

  80. Shelikhova L, Ilushina M, Shekhovtsova Z, Kurnikova E, Novichkova G, Maschan A, et al. Alpha/Beta T cell depleted haploidentical transplantation results in high survival in pediatric patients with acute myeloid leukemia. ASH; Atlanta, GA. Blood. 2017;130:4580.

    Google Scholar 

  81. Liu D, Huang X, Liu K, Xu L, Chen H, Han W, et al. Haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for treatment of hematological malignancies in children. Biol Blood Marrow Transpl. 2008;14:469–77. https://doi.org/10.1016/j.bbmt.2008.02.007

    Article  CAS  Google Scholar 

  82. Liu DH, Xu LP, Liu KY, Wang Y, Chen H, Han W, et al. Long-term outcomes of unmanipulated haploidentical HSCT for paediatric patients with acute leukaemia. Bone Marrow Transpl. 2013;48:1519–24. https://doi.org/10.1038/bmt.2013.99

    Article  Google Scholar 

  83. Chang YJ, Wang Y, Xu LP, Zhang XH, Chen H, Chen YH, et al. Haploidentical donor is preferred over matched sibling donor for pre-transplantation MRD positive ALL: a phase 3 genetically randomized study. J Hematol Oncol. 2020;13:27. https://doi.org/10.1186/s13045-020-00860-y

    Article  PubMed  PubMed Central  Google Scholar 

  84. Xue YJ, Suo P, Huang XJ, Lu AD, Wang Y, Zuo YX, et al. Superior survival of unmanipulated haploidentical haematopoietic stem cell transplantation compared with intensive chemotherapy as post-remission treatment for children with very high-risk philadelphia chromosome negative B-cell acute lymphoblastic leukaemia in first complete remission. Br J Haematol. 2020;188:757–67. https://doi.org/10.1111/bjh.16226

    Article  CAS  PubMed  Google Scholar 

  85. Xue YJ, Cheng YF, Lu AD, Wang Y, Zuo YX, Yan CH, et al. Allogeneic hematopoietic stem cell transplantation, especially haploidentical, may improve long-term survival for high-risk pediatric patients with philadelphia chromosome-positive acute lymphoblastic leukemia in the tyrosine kinase inhibitor era. Biol Blood Marrow Transpl. 2019;25:1611–20. https://doi.org/10.1016/j.bbmt.2018.12.007

    Article  CAS  Google Scholar 

  86. Chang YJ, Wang Y, Liu YR, Xu LP, Zhang XH, Chen H, et al. Haploidentical allograft is superior to matched sibling donor allograft in eradicating pre-transplantation minimal residual disease of AML patients as determined by multiparameter flow cytometry: a retrospective and prospective analysis. J Hematol Oncol. 2017;10:134. https://doi.org/10.1186/s13045-017-0502-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Trujillo AM, Karduss AJ, Suarez G, Perez R, Ruiz G, Cardona A, et al. Long term follow up of haploidentical peripheral blood stem cell transplantation with post-transplant cyclophosphamide in children and teenagers <18 years old with high-risk acute leukemia. very good results in CR1 and CR2 patients but unexpected high incidence of severe acute graft versus host disease in children <10 years. ASH; 7 december 2017. Blood. 2017;130:4563.

    Google Scholar 

  88. Bolanos-Meade J, Fuchs EJ, Luznik L, Lanzkron SM, Gamper CJ, Jones RJ, et al. HLA-haploidentical bone marrow transplantation with posttransplant cyclophosphamide expands the donor pool for patients with sickle cell disease. Blood. 2012;120:4285–91. https://doi.org/10.1182/blood-2012-07-438408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Raj K, Pagliuca A, Bradstock K, Noriega V, Potter V, Streetly M, et al. Peripheral blood hematopoietic stem cells for transplantation of hematological diseases from related, haploidentical donors after reduced-intensity conditioning. Biol Blood Marrow Transpl. 2014;20:890–5. https://doi.org/10.1016/j.bbmt.2014.03.003

    Article  Google Scholar 

  90. Maschan M, Shelikhova L, Ilushina M, Kurnikova E, Boyakova E, Balashov D, et al. TCR-alpha/beta and CD19 depletion and treosulfan-based conditioning regimen in unrelated and haploidentical transplantation in children with acute myeloid leukemia. Bone Marrow Transpl. 2016;51:668–74. https://doi.org/10.1038/bmt.2015.343

    Article  CAS  Google Scholar 

  91. Maschan M, Shelikhova L, Ilushina M, Shekhovtsova Z, Khismatullina R, Kurnikova E, et al. Outcome of alphabeta T cell-depleted transplantation in children with high-risk acute myeloid leukemia, grafted in remission. Bone Marrow Transpl. 2020;55:256–9. https://doi.org/10.1038/s41409-019-0531-3

    Article  Google Scholar 

  92. Bleakley M, Heimfeld S, Loeb KR, Jones LA, Chaney C, Seropian S, et al. Outcomes of acute leukemia patients transplanted with naive T cell-depleted stem cell grafts. J Clin Investig. 2015;125:2677–89. https://doi.org/10.1172/JCI81229

    Article  PubMed  PubMed Central  Google Scholar 

  93. Triplett BM, Shook DR, Eldridge P, Li Y, Kang G, Dallas M, et al. Rapid memory T-cell reconstitution recapitulating CD45RA-depleted haploidentical transplant graft content in patients with hematologic malignancies. Bone Marrow Transpl. 2015;50:1012. https://doi.org/10.1038/bmt.2015.139

    Article  CAS  Google Scholar 

  94. Mamcarz E, Madden R, Qudeimat A, Srinivasan A, Talleur A, Sharma A, et al. Improved survival rate in T-cell depleted haploidentical hematopoietic cell transplantation over the last 15 years at a single institution. Bone Marrow Transpl. 2020;55:929–38. https://doi.org/10.1038/s41409-019-0750-7

    Article  CAS  Google Scholar 

  95. Perez-Martinez A, Ferreras C, Pascual A, Gonzalez-Vicent M, Alonso L, Badell I, et al. Haploidentical transplantation in high-risk pediatric leukemia: a retrospective comparative analysis on behalf of the Spanish working Group for bone marrow transplantation in children (GETMON) and the Spanish Grupo for hematopoietic transplantation (GETH). Am J Hematol. 2020;95:28–37. https://doi.org/10.1002/ajh.25661

    Article  CAS  PubMed  Google Scholar 

  96. Zheng FM, Zhang X, Li CF, Cheng YF, Gao L, He YL, et al. Haploidentical- versus identical-sibling transplant for high-risk pediatric AML: a multi-center study. Cancer Commun (Lond). 2020;40:93–104. https://doi.org/10.1002/cac2.12014

    Article  Google Scholar 

  97. Huang XJ, Liu DH, Liu KY, Xu LP, Chen H, Han W, et al. Haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion for the treatment of hematological malignancies. Bone Marrow Transpl. 2006;38:291–7. https://doi.org/10.1038/sj.bmt.1705445

    Article  Google Scholar 

  98. Arcese W, Picardi A, Santarone S, De Angelis G, Cerretti R, Cudillo L, et al. Haploidentical, G-CSF-primed, unmanipulated bone marrow transplantation for patients with high-risk hematological malignancies: an update. Bone Marrow Transpl. 2015;50:S24–30. https://doi.org/10.1038/bmt.2015.91

    Article  CAS  Google Scholar 

  99. Wang Y, Chang YJ, Chen L, Xu LP, Bian ZL, Zhang XH, et al. Low-dose post-transplant cyclophosphamide can mitigate GVHD and enhance the G-CSF/ATG induced GVHD protective activity and improve haploidentical transplant outcomes. Oncoimmunology. 2017;6:e1356152. https://doi.org/10.1080/2162402X.2017.1356152

    Article  PubMed  PubMed Central  Google Scholar 

  100. Kanakry CG, Coffey DG, Towlerton AM, Vulic A, Storer BE, Chou J, et al. Origin and evolution of the T cell repertoire after posttransplantation cyclophosphamide. JCI Insight. 2016;1:e86252. https://doi.org/10.1172/jci.insight.86252

    Article  PubMed  PubMed Central  Google Scholar 

  101. Shah NN, Freeman AF, Su H, Cole K, Parta M, Moutsopoulos NM, et al. Haploidentical related donor hematopoietic stem cell transplantation for dedicator-of-cytokinesis 8 deficiency using post-transplantation cyclophosphamide. Biol Blood Marrow Transpl. 2017;23:980–90. https://doi.org/10.1016/j.bbmt.2017.03.016

    Article  CAS  Google Scholar 

  102. Roberto A, Di Vito C, Zaghi E, Mazza EMC, Capucetti A, Calvi M, et al. The early expansion of anergic NKG2A(pos)/CD56(dim)/CD16(neg) natural killer represents a therapeutic target in haploidentical hematopoietic stem cell transplantation. Haematologica. 2018;103:1390–402. https://doi.org/10.3324/haematol.2017.186619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Brunstein CG, Fuchs EJ, Carter SL, Karanes C, Costa LJ, Wu J, et al. Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts. Blood. 2011;118:282–8. https://doi.org/10.1182/blood-2011-03-344853

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Stabile H, Nisti P, Peruzzi G, Fionda C, Pagliara D, Brescia PL, et al. Reconstitution of multifunctional CD56(low)CD16(low) natural killer cell subset in children with acute leukemia given alpha/beta T cell-depleted HLA-haploidentical haematopoietic stem cell transplantation. Oncoimmunology. 2017;6:e1342024. https://doi.org/10.1080/2162402X.2017.1342024

    Article  PubMed  Google Scholar 

  105. Bertaina A, Zorzoli A, Petretto A, Barbarito G, Inglese E, Merli P, et al. Zoledronic acid boosts gammadelta T-cell activity in children receiving alphabeta(+) T and CD19(+) cell-depleted grafts from an HLA-haplo-identical donor. Oncoimmunology. 2017;6:e1216291. https://doi.org/10.1080/2162402X.2016.1216291

    Article  CAS  PubMed  Google Scholar 

  106. Meeh PF, King M, O’Brien RL, Muga S, Buckhalts P, Neuberg R, et al. Characterization of the gammadelta T cell response to acute leukemia. Cancer Immunol Immunother. 2006;55:1072–80. https://doi.org/10.1007/s00262-005-0094-6

    Article  PubMed  Google Scholar 

  107. Locatelli F, Pende D, Falco M, Della Chiesa M, Moretta A, Moretta L. NK cells mediate a crucial graft-versus-leukemia effect in haploidentical-HSCT to cure high-risk acute leukemia. Trends Immunol. 2018;39:577–90. https://doi.org/10.1016/j.it.2018.04.009

    Article  CAS  PubMed  Google Scholar 

  108. Gao F, Ye Y, Gao Y, Huang H, Zhao Y. Influence of KIR and NK cell reconstitution in the outcomes of hematopoietic stem cell transplantation. Front Immunol. 2020;11:2022. https://doi.org/10.3389/fimmu.2020.02022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Huang XJ, Zhao XY, Liu DH, Liu KY, Xu LP. Deleterious effects of KIR ligand incompatibility on clinical outcomes in haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion. Leukemia. 2007;21:848–51. https://doi.org/10.1038/sj.leu.2404566

    Article  CAS  PubMed  Google Scholar 

  110. Wanquet A, Bramanti S, Harbi S, Furst S, Legrand F, Faucher C, et al. Killer cell immunoglobulin-like receptor-ligand mismatch in donor versus recipient direction provides better graft-versus-tumor effect in patients with hematologic malignancies undergoing allogeneic T cell-replete haploidentical transplantation followed by post-transplant cyclophosphamide. Biol Blood Marrow Transpl. 2018;24:549–54. https://doi.org/10.1016/j.bbmt.2017.11.042

    Article  CAS  Google Scholar 

  111. Shimoni A, Labopin M, Lorentino F, Van Lint MT, Koc Y, Gülbas Z, et al. Killer cell immunoglobulin-like receptor ligand mismatching and outcome after haploidentical transplantation with post-transplant cyclophosphamide. Leukemia. 2018;33:230–9. https://doi.org/10.1038/s41375-018-0170-5

    Article  CAS  PubMed  Google Scholar 

  112. Chang YJ, Zhao XS, Wang Y, Liu YR, Xu LP, Zhang XH, et al. Effects of pre- and post-transplantation minimal residual disease on outcomes in pediatric patients with acute myeloid leukemia receiving human leukocyte antigen-matched or mismatched related donor allografts. Am J Hematol. 2017;92:E659–E661. https://doi.org/10.1002/ajh.24910

    Article  CAS  PubMed  Google Scholar 

  113. Mo XD, Zhang XH, Xu LP, Wang Y, Yan CH, Chen H, et al. Unmanipulated haploidentical hematopoietic stem cell transplantation in first complete remission can abrogate the poor outcomes of children with acute myeloid leukemia resistant to the first course of induction chemotherapy. Biol Blood Marrow Transpl. 2016;22:2235–42. https://doi.org/10.1016/j.bbmt.2016.09.004

    Article  Google Scholar 

  114. Tang FF, Cheng YF, Xu LP, Zhang XH, Yan CH, Han W, et al. Incidence, risk factors, and outcomes of chronic graft-versus-host disease in pediatric patients with hematologic malignancies after T cell-replete myeloablative haploidentical hematopoietic stem cell transplantation with antithymocyte globulin/granulocyte colony-stimulating factor. Biol Blood Marrow Transpl. 2020;26:1655–62. https://doi.org/10.1016/j.bbmt.2020.05.021

    Article  CAS  Google Scholar 

  115. Rovatti PE, Gambacorta V, Lorentino F, Ciceri F, Vago L. Mechanisms of leukemia immune evasion and their role in relapse after haploidentical hematopoietic cell transplantation. Front Immunol. 2020;11:147. https://doi.org/10.3389/fimmu.2020.00147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Zhang C, Ma YY, Liu J, Liu Y, Gao L, Gao L, et al. Preventive infusion of donor-derived CAR-T cells after haploidentical transplantation: two cases report. Med (Baltim). 2019;98:e16498. https://doi.org/10.1097/MD.0000000000016498

    Article  Google Scholar 

  117. Wiebking V, Lee CM, Mostrel N, Lahiri P, Bak R, Bao G et al. Genome editing of donor-derived T-cells to generate allogenic chimeric antigen receptor-modified T cells: Optimizing alphabeta T cell-depleted haploidentical hematopoietic stem cell transplantation. Haematologica. 2020;105. https://doi.org/10.3324/haematol.2019.233882

  118. Radojcic V, Luznik L. Mechanism of action of posttransplantation cyclophosphamide: more than meets the eye. J Clin Invest. 2019;130:2189–91. https://doi.org/10.1172/JCI128710

    Article  Google Scholar 

  119. Zvyagin IV, Mamedov IZ, Tatarinova OV, Komech EA, Kurnikova EE, Boyakova EV, et al. Tracking T-cell immune reconstitution after TCRalphabeta/CD19-depleted hematopoietic cells transplantation in children. Leukemia. 2017;31:1145–53. https://doi.org/10.1038/leu.2016.321

    Article  CAS  PubMed  Google Scholar 

  120. Bolanos-Meade J, Cooke KR, Gamper CJ, Ali SA, Ambinder RF, Borrello IM, et al. Effect of increased dose of total body irradiation on graft failure associated with HLA-haploidentical transplantation in patients with severe haemoglobinopathies: a prospective clinical trial. Lancet Haematol. 2019;6:e183–e193. https://doi.org/10.1016/S2352-3026(19)30031-6

    Article  PubMed  PubMed Central  Google Scholar 

  121. Laberko A, Bogoyavlenskaya A, Shelikhova L, Shekhovtsova Z, Balashov D, Voronin K, et al. Risk factors for and the clinical impact of cytomegalovirus and Epstein-Barr virus infections in pediatric recipients of TCR-alpha/beta- and CD19-depleted grafts. Biol Blood Marrow Transpl. 2017;23:483–90. https://doi.org/10.1016/j.bbmt.2016.12.635

    Article  Google Scholar 

  122. Triplett BM, Muller B, Kang G, Li Y, Cross SJ, Moen J, et al. Selective T-cell depletion taHaplo-HSCTrgeting CD45RA reduces viremia and enhances early T-cell recovery compared with CD3-targeted T-cell depletion. Transpl Infect Dis. 2018;20:e12823. https://doi.org/10.1111/tid.12823

    Article  CAS  Google Scholar 

  123. Sisinni L, Gasior M, de Paz R, Querol S, Bueno D, Fernandez L, et al. Unexpected high incidence of human Herpesvirus-6 encephalitis after naive T cell-depleted graft of haploidentical stem cell transplantation in pediatric patients. Biol Blood Marrow Transpl. 2018;24:2316–23. https://doi.org/10.1016/j.bbmt.2018.07.016

    Article  Google Scholar 

  124. Bertaina A, Roncarolo MG. Graft engineering and adoptive immunotherapy: new approaches to promote immune tolerance after hematopoietic stem cell transplantation. Front Immunol. 2019;10:1342. https://doi.org/10.3389/fimmu.2019.01342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Gonzalez-Llano O, Gonzalez-Lopez EE, Ramirez-Cazares AC, Marcos-Ramirez ER, Ruiz-Arguelles GJ, Gomez-Almaguer D. Haploidentical peripheral blood stem cell transplantation with posttransplant cyclophosphamide in children and adolescents with hematological malignancies. Pediatr Blood Cancer. 2016;63:2033–7. https://doi.org/10.1002/pbc.26131

    Article  CAS  PubMed  Google Scholar 

  126. Lang PJ, Schlegel PG, Meisel R, Schulz AS, Greil J, Bader P, et al. TCR-alpha/beta and CD19 depleted haploidentical stem cell transplantation following reduced intensity conditioning in children: first results of a prospective multicenter phase I/II clinical trial. Blood. 2016;128:389–389.

    Article  Google Scholar 

  127. Erbey F, Akcay A, Atay D, Ovali E, Ozturk G. Comparison of outcomes after HLA-matched unrelated and alphabeta T-cell-depleted haploidentical hematopoietic stem cell transplantation for children with high-risk acute leukemia. Pediatr Transpl. 2018;22:e13192. https://doi.org/10.1111/petr.13192

    Article  CAS  Google Scholar 

  128. Chen H, Liu KY, Xu LP, Chen YH, Zhang XH, Wang Y, et al. Haploidentical hematopoietic stem cell transplantation for pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia in the imatinib era. Leuk Res. 2017;59:136–41. https://doi.org/10.1016/j.leukres.2017.05.021

    Article  CAS  PubMed  Google Scholar 

  129. Bai L, Cheng YF, Lu AD, Suo P, Wang Y, Zuo YX, et al. Prognosis of haploidentical hematopoietic stem cell transplantation in non-infant children with t(v;11q23)/MLL-rearranged B-cell acute lymphoblastic leukemia. Leuk Res. 2020;91:106333. https://doi.org/10.1016/j.leukres.2020.106333

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Grateful to Dr Regina M Nolan (Haematology, Bristol Royal Infirmary, Bristol, UK) and Ms Karen Mazil (Research nurse, Pediatric Oncology, Alberta Children’s Hospital, Calgary) for help with English editing.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ravi M. Shah.

Ethics declarations

Conflict of interest

The author declares no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shah, R.M. Contemporary haploidentical stem cell transplant strategies in children with hematological malignancies. Bone Marrow Transplant 56, 1518–1534 (2021). https://doi.org/10.1038/s41409-021-01246-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-021-01246-5

Search

Quick links