Haploidentical Transplants: Nonmalignant Diseases in Adults

  • Javier Bolaños Meade
Part of the Advances and Controversies in Hematopoietic Transplantation and Cell Therapy book series (ACHTCT)


Haploidentical transplantation is becoming a common practice in recent times particularly after the introduction of post-transplant cyclophosphamide by the Johns Hopkins group (Luznik et al. Biol Blood Marrow Transplant 14(6):641–650, 2008; Bacigalupo et al. Adv Hematol 2016:7802967, 2016). In the past, the excessive morbidity and mortality caused by the HLA-mismatched transplant made this intervention very high risk for treatment-related mortality, but nowadays it appears that the outcomes are similar to those of HLA-matched transplants, i.e., HLA-matched, related, or unrelated (Ciurea et al. Blood 126(8):1033–1040, 2015; Kanate et al. Blood 127(7):938–947, 2016; Ghosh et al. J Clin Oncol 34(26):3141–3149, 2016). In fact, they appear to compare well with other alternative donors such as cord transplants (Brunstein et al. Blood 118(2):282–288, 2011). There are many potential advantages in using haploidentical donors as alternative donors when needed. Given that the toxicity seen in haploidentical transplants is not different compared with other types of allogeneic transplant approaches, its use in hereditary nonmalignant disorders seems logical for exploration. In this chapter, the results of such approach in patients with hereditary nonmalignant disorders will be reviewed.


Haploidentical transplant GvHD CD34 T-cell depletion G-CSF Graft Sickle cell disease Thalassemia Hereditary Conditioning Nonmalignant Benign Immunodeficiency Chimera 


  1. 1.
    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 Transplant. 2008;14(6):641–50.CrossRefGoogle Scholar
  2. 2.
    Bacigalupo A, Sica S. HLA haplotype mismatch transplants and posttransplant cyclophosphamide. Adv Hematol. 2016;2016:7802967.CrossRefGoogle Scholar
  3. 3.
    Ciurea SO, Zhang MJ, Bacigalupo AA, Bashey A, Appelbaum FR, Aljitawi OS, et al. Haploidentical transplant with posttransplant cyclophosphamide vs matched unrelated donor transplant for acute myeloid leukemia. Blood. 2015;126(8):1033–40.CrossRefGoogle Scholar
  4. 4.
    Kanate AS, Mussetti A, Kharfan-Dabaja MA, Ahn KW, DiGilio A, Beitinjaneh A, et al. Reduced-intensity transplantation for lymphomas using haploidentical related donors vs HLA-matched unrelated donors. Blood. 2016;127(7):938–47.CrossRefGoogle Scholar
  5. 5.
    Ghosh N, Rocha V, Ahn KW, DiGilio A, Hari P, Bachanova V, et al. Reduced-intensity transplantation for lymphomas using haploidentical related donors versus HLA-matched sibling donors. A CIBMTR analysis. J Clin Oncol. 2016;34(26):3141–9.CrossRefGoogle Scholar
  6. 6.
    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(2):282–8.CrossRefGoogle Scholar
  7. 7.
    Piel FB, Hay SI, Gupta S, Weatherall DJ, Williams TN. Global burden of sickle cell anaemia in children under five, 2010-2050: modelling based on demographics, excess mortality, and interventions. PLoS Med. 2013;10(7):e1001484.CrossRefGoogle Scholar
  8. 8.
    Kauf TL, Coates TD, Huazhi L, Mody-Patel N, Hartzema AG. The cost of health care for children and adults with sickle cell disease. Am J Hematol. 2009;84(6):323–7.CrossRefGoogle Scholar
  9. 9.
    Ballas SK, Bauserman RL, McCarthy WF, Waclawiw MA. The impact of hydroxyurea on career and employment of patients with sickle cell anemia. J Natl Med Assoc. 2010;102(11):993–9.CrossRefGoogle Scholar
  10. 10.
    Johnson FL, Look AT, Gockerman J, Ruggiero MR, la-Pozza L, Billings FT III. Bone-marrow transplantation in a patient with sickle-cell anemia. N Engl J Med. 1984;311(12):780–3.CrossRefGoogle Scholar
  11. 11.
    Bernaudin F, Souillet G, Vannier JP, Plouvier E, Lemerle S, Michel G, et al. Treatment of severe forms of sickle cell anemia with bone marrow allograft: French experience (15 cases). SFGM. Nouv Rev Fr Hematol. 1993;35(3):319–23.PubMedGoogle Scholar
  12. 12.
    Walters MC, Patience M, Leisenring W, Eckman JR, Scott JP, Mentzer WC, et al. Bone marrow transplantation for sickle cell disease. N Engl J Med. 1996;335(6):369–76.CrossRefGoogle Scholar
  13. 13.
    Walters MC, Patience M, Leisenring W, Eckman JR, Buchanan GR, Rogers ZR, et al. Barriers to bone marrow transplantation for sickle cell anemia. Biol Blood Marrow Transplant. 1996;2(2):100–4.PubMedGoogle Scholar
  14. 14.
    Hsieh MM, Kang EM, Fitzhugh CD, Link MB, Bolan CD, Kurlander R, et al. Allogeneic hematopoietic stem-cell transplantation for sickle cell disease. N Engl J Med. 2009;361(24):2309–17.CrossRefGoogle Scholar
  15. 15.
    Gluckman E. Allogeneic transplantation strategies including haploidentical transplantation in sickle cell disease. Hematology Am Soc Hematol Educ Program. 2013;2013:370–6.PubMedGoogle Scholar
  16. 16.
    Bolaños-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(22):4285–91.CrossRefGoogle Scholar
  17. 17.
    Hulbert ML, McKinstry RC, Lacey JL, Moran CJ, Panepinto JA, Thompson AA, et al. Silent cerebral infarcts occur despite regular blood transfusion therapy after first strokes in children with sickle cell disease. Blood. 2011;117(3):772–9.CrossRefGoogle Scholar
  18. 18.
    Chakrabarti S, Bareford D. A survey on patient perception of reduced-intensity transplantation in adults with sickle cell disease. Bone Marrow Transplant. 2007;39(8):447–51.CrossRefGoogle Scholar
  19. 19.
    Bernaudin F, Socie G, Kuentz M, Chevret S, Duval M, Bertrand Y, et al. Long-term results of related myeloablative stem-cell transplantation to cure sickle cell disease. Blood. 2007;110(7):2749–56.CrossRefGoogle Scholar
  20. 20.
    Vermylen C, Cornu G, Ferster A, Brichard B, Ninane J, Ferrant A, et al. Haematopoietic stem cell transplantation for sickle cell anaemia: the first 50 patients transplanted in Belgium. Bone Marrow Transplant. 1998;22(1):1–6.CrossRefGoogle Scholar
  21. 21.
    Walters MC, Storb R, Patience M, Leisenring W, Taylor T, Sanders JE, et al. Impact of bone marrow transplantation for symptomatic sickle cell disease: an interim report. Multicenter investigation of bone marrow transplantation for sickle cell disease. Blood. 2000;95(6):1918–24.PubMedGoogle Scholar
  22. 22.
    Locatelli F, Kabbara N, Ruggeri A, Ghavamzadeh A, Roberts I, Li CK, et al. Outcome of patients with hemoglobinopathies given either cord blood or bone marrow transplantation from an HLA-identical sibling. Blood. 2013;122(6):1072–8.CrossRefGoogle Scholar
  23. 23.
    Jacobsohn DA, Duerst R, Tse W, Kletzel M. Reduced intensity haemopoietic stem-cell transplantation for treatment of non-malignant diseases in children. Lancet. 2004;364(9429):156–62.CrossRefGoogle Scholar
  24. 24.
    Horwitz ME, Spasojevic I, Morris A, Telen M, Essell J, Gasparetto C, et al. Fludarabine-based nonmyeloablative stem cell transplantation for sickle cell disease with and without renal failure: clinical outcome and pharmacokinetics. Biol Blood Marrow Transplant. 2007;13(12):1422–6.CrossRefGoogle Scholar
  25. 25.
    Iannone R, Casella JF, Fuchs EJ, Chen AR, Jones RJ, Woolfrey A, et al. Results of minimally toxic nonmyeloablative transplantation in patients with sickle cell anemia and beta-thalassemia. Biol Blood Marrow Transplant. 2003;9(8):519–28.CrossRefGoogle Scholar
  26. 26.
    Hsieh MM, Fitzhugh CD, Weitzel R. Nonmyeloablative HLA-matched sibling allogeneic hematopoietic stem cell transplantation for severe sickle cell phenotype. JAMA. 2014;312(1):48–56.CrossRefGoogle Scholar
  27. 27.
    Kharbanda S, Smith AR, Hutchinson SK, McKenna DH, Ball JB, Lamb LS Jr, et al. Unrelated donor allogeneic hematopoietic stem cell transplantation for patients with hemoglobinopathies using a reduced-intensity conditioning regimen and third-party mesenchymal stromal cells. Biol Blood Marrow Transplant. 2014;20(4):581–6.CrossRefGoogle Scholar
  28. 28.
    Adamkiewicz TV, Szabolcs P, Haight A, Baker KS, Staba S, Kedar A, et al. Unrelated cord blood transplantation in children with sickle cell disease: review of four-center experience. Pediatr Transplant. 2007;11(6):641–4.CrossRefGoogle Scholar
  29. 29.
    Kamani NR, Walters MC, Carter S, Aquino V, Brochstein JA, Chaudhury S, et al. Unrelated donor cord blood transplantation for children with severe sickle cell disease: results of one cohort from the phase II study from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). Biol Blood Marrow Transplant. 2012;18(8):1265–72.CrossRefGoogle Scholar
  30. 30.
    Doney K, Dahlberg SJ, Monroe D, Storb R, Buckner CD, Thomas ED. Therapy of severe aplastic anemia with anti-human thymocyte globulin and androgens: the effect of HLA-haploidentical marrow infusion. Blood. 1984;63(2):342–8.PubMedGoogle Scholar
  31. 31.
    Bishop MR, Henslee-Downey PJ, Anderson JR, Romond EH, Marciniak E, Yankey R, et al. Long-term survival in advanced chronic myelogenous leukemia following bone marrow transplantation from haploidentical related donors. Bone Marrow Transplant. 1996;18(4):747–53.PubMedGoogle Scholar
  32. 32.
    Brodsky RA, Luznik L, Bolaños-Meade J, Leffell MS, Jones RJ, Fuchs EJ. Reduced intensity HLA-haploidentical BMT with post transplantation cyclophosphamide in nonmalignant hematologic diseases. Bone Marrow Transplant. 2008;42(8):523–7.CrossRefGoogle Scholar
  33. 33.
    de la Fuente J, O’Boyle F, Harrington Y, Bradshaw A, Hind S, Chakravorty S, et al. Haploidentical BMT with a post-infusion of stem cells cyclophosphamide approach is feasible and leads to a high rate of donor engraftment in haemoglobinopathies allowing universal application of transplantation. Blood. 2015;126(23):4317.Google Scholar
  34. 34.
    Pai SY, Logan BR, Griffith LM, Buckley RH, Parrott RE, Dvorak CC, et al. Transplantation outcomes for severe combined immunodeficiency, 2000-2009. N Engl J Med. 2014;371(5):434–46.CrossRefGoogle Scholar
  35. 35.
    Reisner Y, Kapoor N, Kirkpatrick D, Pollack MS, Cunningham-Rundles S, Dupont B, 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. 1983;61(2):341–8.PubMedGoogle Scholar
  36. 36.
    Cowan MJ, Wara DW, Weintrub PS, Pabst H, Ammann AJ. Haploidentical bone marrow transplantation for severe combined immunodeficiency disease using soybean agglutinin-negative, T-depleted marrow cells. J Clin Immunol. 1985;5(6):370–6.CrossRefGoogle Scholar
  37. 37.
    Tsuji Y, Imai K, Kajiwara M, Aoki Y, Isoda T, Tomizawa D, et al. Hematopoietic stem cell transplantation for 30 patients with primary immunodeficiency diseases: 20 years experience of a single team. Bone Marrow Transplant. 2006;37(5):469–77.CrossRefGoogle Scholar
  38. 38.
    Dezern AE, Dorr D, Luznik L, Bolaños-Meade J, Gamper C, Symons HJ, et al. Using Haploidentical (haplo) donors and high-dose post-transplant cyclophosphamide (PTCy) for refractory severe aplastic anemia (SAA). Blood. 2015;126(23):2031.Google Scholar
  39. 39.
    Hickstein DD, Shah NN, Freeman AF, Zerbe C, Holland SM, Parta M. Allogeneic hematopoietic stem cell transplant for GATA2 deficiency. Blood. 2015;126(23):1500.Google Scholar
  40. 40.
    Zecca M, Strocchio L, Pagliara D, Comoli P, Bertaina A, Giorgiani G, et al. HLA-haploidentical T cell-depleted allogeneic hematopoietic stem cell transplantation in children with Fanconi anemia. Biol Blood Marrow Transplant. 2014;20(4):571–6.CrossRefGoogle Scholar
  41. 41.
    Gondek LP, Zheng G, Ghiaur G, Dezern AE, Matsui W, Yegnasubramanian S, et al. Donor cell leukemia arising from clonal hematopoiesis after bone marrow transplantation. Leukemia. 2016;30(9):1916–20.CrossRefGoogle Scholar
  42. 42.
    Zeidan AM, Forde PM, Symons H, Chen A, Smith BD, Pratz K, et al. HLA-haploidentical donor lymphocyte infusions for patients with relapsed hematologic malignancies after related HLA-haploidentical bone marrow transplantation. Biol Blood Marrow Transplant. 2014;20(3):314–8.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Adult Bone Marrow Transplant ProgramThe Sidney Kimmel Comprehensive Cancer Center and Johns Hopkins University School of MedicineBaltimoreUSA

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