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Hematopoietic stem cell transplantation for adult sickle cell disease in the era of universal donor availibility

Bone Marrow Transplantation volume 53, pages 1390–1400 (2018)Cite this article

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Abstract

Current projections estimate that the number of newborns with sickle cell disease (SCD) globally will exceed 400,000 by 2050. Over the last three decades, increased newborn screening, supportive care, and use of hydroxyurea therapy, have decreased early childhood mortality among individuals affected with SCD. Despite hematopoietic cell transplantation (HCT) being curative in SCD, its impact on disease free survival remains unknown, especially in adults, partly due to previous limitations in donor options and perceived mortality in adults using myeloablative conditioning. Novel non-myeloablative or reduced intensity conditioning regimens have made HCT safer and applicable to adults with SCD who were previously excluded. Other reasons for limited use of HCT in SCD includes referral bias, provider preference, poor education of patient/families, perceived procedure risks, costs and limited logistic resources in both low income, middle income, and high income countries. Current data from landmark studies indicate that both the long-term disease-free survival and overall survival exceed 90% after matched sibling donor HCT in children. Improving transplant outcomes and expanding donor pool will increase the use of transplant for SCD, especially in affected adults. On-going investigations using matched umbilical cord units, unrelated matched donor, and related haploidentical donors, promises to make HCT a viable option for nearly all eligible patients with SCD. This systematic review focuses on the recent data for HCT for patients with adult SCD with particular emphasis on donor sources and availability as illustrated by a case presentation exhibiting real world issues.

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References

  1. Xu L-H, Fang J-P, Xu H-G, Weng W-J. Homing and engraftment of bone marrow cells derived from different donors in a murine model of sensitization. Hematology. 2012;17:215–19.

    Article  PubMed  Google Scholar 

  2. Van Besien K, Bartholomew A, Stock W, Peace D. Fludarabine-based conditioning for allogeneic transplantation in adults with sickle cell disease. Bone Marrow transplant. 2000;26:445-9.

    Article  PubMed  Google Scholar 

  3. Oringanje C, Nemecek E, Oniyangi O. Hematopoietic stem cell transplantation for people with sickle cell disease. Cochrane Library. 2016;CD007001.

  4. Oringanje C, Nemecek E, Oniyangi O. Hematopoietic stem cell transplantation for children with sickle cell disease. Cochrane Library. 2009;CD007001.

  5. Gluckman E, Cappelli B, Bernaudin F, Labopin M, Volt F, et al. Sickle cell disease: an international survey of results of HLA-identical sibling hematopoietic stem cell transplantation. Blood. 2017;129:1548–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Shenoy S. Hematopoietic stem-cell transplantation for sickle cell disease: current evidence and opinions. Ther Adv Hematol. 2013;4:335–44.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Shenoy S. Hematopoietic stem cell transplantation for sickle cell disease: current practice and emerging trends. Hematol Am Soc Hematol Educ Program. 2011;2011:273–79.

    Article  Google Scholar 

  8. Holtick U, Albrecht M, Chemnitz JM, Theurich S, Skoetz N. Bone marrow versus peripheral blood allogeneic haematopoietic stem cell transplantation for haematological malignancies in adults. Cochrane Database Syst Rev 2014;C010189.

  9. Bolanos-Meade J, Fuchs EJ, Luznik L, Lanzkron SM, Gamper CJ. HLA-haploidentical bone marrow transplantation with posttransplant cyclophosphamide expands the donor pool for patients with sickle cell disease. Blood. 2012;120:4285–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Anasetti C, Logan BR, Lee SJ, Waller EK, Weisdorf DJ, et al. Peripheral-blood stem cells versus bone marrow from unrelated donors. New Engl J Med. 2012;367:1487–96.

    Article  CAS  PubMed  Google Scholar 

  11. Rezvani K, Flanagan AM, Sarma U, Constantinovici N, Bain BJ. Investigation of ethnic neutropenia by assessment of bone marrow colony-forming cells. Acta Haematol. 2001;105:32–7.

    Article  CAS  PubMed  Google Scholar 

  12. Ozdogu H, Boga C. Hematopoietic stem cell transplantation in adult sickle cell disease: problems and solutions. Turk J Haematol. 2015;32:195–205.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Luznik L, Fuchs EJ. High-dose, post-transplantation cyclophosphamide to promote graft-host tolerance after allogeneic hematopoietic stem cell transplantation. Immunol Res. 2010;47:65–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Knuppel E, Medinger M, Stehle G, Infanti L, Halter J. Haploidentical hematopoietic bone marrow transplantation followed by living kidney transplantation from the same donor in a sickle cell disease patient with end-stage renal failure. Ann Hematol. 2017;96:703–5.

    Article  PubMed  Google Scholar 

  15. Woodard P, Lubin B, Walters CM. New approaches to hematopoietic cell transplantation for hematological diseases in children. Pediatr Clin North Am. 2002;49:989–1007.

    Article  PubMed  Google Scholar 

  16. Brodsky RA, Luznik L, Bolanos-Meade J, Leffell MS, Jones RJ. Reduced intensity HLA-haploidentical BMT with post transplantation cyclophosphamide in nonmalignant hematologic diseases. Bone Marrow Transplant. 2008;42:523–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Sodani P, Isgro A, Gaziev J, Polchi P, Paciaroni K, et al. Purified T-depleted, CD34 + peripheral blood and bone marrow cell transplantation from haploidentical mother to child with thalassemia. Blood. 2010;115:1296–302.

    Article  CAS  PubMed  Google Scholar 

  18. Isgro A, Marziali M, Sodani P, Gaziev J, Erer B, et al. Immunohematologic reconstitution in pediatric patients after T cell-depleted HLA-haploidentical stem cell transplantation for thalassemia. Biol Blood Marrow Transplant. 2010;16:1557–66.

    Article  PubMed  Google Scholar 

  19. Gragert L, Eapen M, Williams E, Freeman J, Spellman S, et al. HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry. New Engl J Med. 2014;371:339–48.

    Article  CAS  PubMed  Google Scholar 

  20. Foell J, Pfirstinger B, Rehe K, Wolff D, Holler E. Haploidentical stem cell transplantation with CD3(+)-/CD19(+)- depleted peripheral stem cells for patients with advanced stage sickle cell disease and no alternative donor: results of a pilot study. Bone Marrow Transplant. 2017;52:938–40.

    Article  CAS  PubMed  Google Scholar 

  21. Poire X, van Besien K. Alemtuzumab in allogeneic hematopoetic stem cell transplantation. Expert Opin Biol Ther. 2011;11:1099–111.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Luznik L, Bolanos-Meade J, Zahurak M, Chen AR, Smith BD, et al. High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease. Blood. 2010;115:3224–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Luznik L, O’Donnell PV, Symons HJ, Chen AR, Leffell MS, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008;14:641–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Locatelli F, Kabbara N, Ruggeri A, Ghavamzadeh A, Roberts I, et al. Outcome of patients with hemoglobinopathies given either cord blood or bone marrow transplantation from an HLA-identical sibling. Blood. 2013;122:1072–8.

    Article  CAS  PubMed  Google Scholar 

  25. Shenoy S. Umbilical cord blood: an evolving stem cell source for sickle cell disease transplants. Stem Cells Transl Med. 2013;2:337–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kamani NR, Walters MC, Carter S, Aquino V, Brochstein JA, 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;18:1265–72.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Ruggeri A, Eapen M, Scaravadou A, Cairo MS, Bhatia M, et al. Umbilical cord blood transplantation for children with thalassemia and sickle cell disease. Biol Blood Marrow Transplant. 2011;17:1375–82.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Dahlberg A, Brashem-Stein C, Delaney C, Bernstein ID. Enhanced generation of cord blood hematopoietic stem and progenitor cells by culture with StemRegenin1 and Delta1(Ext-IgG.). Leukemia. 2014;28:2097–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Horwitz ME, Chao NJ, Rizzieri DA, Long GD, Sullivan KM, et al. Umbilical cord blood expansion with nicotinamide provides long-term multilineage engraftment. J Clin Investig. 2014;124:3121–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kharbanda S, Smith AR, Hutchinson SK, McKenna DH. 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;20:581–6.

    Article  PubMed  Google Scholar 

  31. 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;84:323–7.

    Article  PubMed  Google Scholar 

  32. Platt OS, Brambilla DJ, Rosse WF, Milner PF. Mortality in sickle cell disease. Life expectancy and risk factors for early death. New Engl J Med. 1994;330:1639–44.

    Article  CAS  PubMed  Google Scholar 

  33. Wayne AS, Schoenike SE, Pegelow CH. Financial analysis of chronic transfusion for stroke prevention in sickle cell disease. Blood. 2000;96:2369–72.

    CAS  PubMed  Google Scholar 

  34. Vermylen C, Cornu G, Ferster A, Brichard B, Ninane J. Haematopoietic stem cell transplantation for sickle cell anaemia: the first 50 patients transplanted in Belgium. Bone Marrow Transplant. 1998;22:1–6.

    Article  CAS  PubMed  Google Scholar 

  35. Bernaudin F, Socie G, Kuentz M, Chevret S, Duval M. Long-term results of related myeloablative stem-cell transplantation to cure sickle cell disease. Blood. 2007;110:2749–56.

    Article  CAS  PubMed  Google Scholar 

  36. Lucarelli G, Gaziev J, Isgrò A, Sodani P, Paciaroni K. Allogeneic cellular gene therapy in hemoglobinopathies—evaluation of hematopoietic SCT in sickle cell anemia. Bone Marrow Transplant. 2012;47:227–30.

    Article  CAS  PubMed  Google Scholar 

  37. Panepinto JA, Walters MC, Carreras J, Marsh J, Bredeson CN, et al. Matched-related donor transplantation for sickle cell disease: report from the Center for International Blood and Transplant Research. Br J Haematol. 2007;137:479–85.

    Article  PubMed  Google Scholar 

  38. Vassiliou G, Amrolia P, Roberts IA. Allogeneic transplantation for haemoglobinopathies. Best Pract Res Clin Haematol. 2001;14:807–22.

    Article  CAS  PubMed  Google Scholar 

  39. Hsieh MM, Kang EM, Fitzhugh CD, Link MB, Bolan CD. Allogeneic hematopoietic stem-cell transplantation for sickle cell disease. New Engl J Med. 2009;361:2309–17.

    Article  CAS  PubMed  Google Scholar 

  40. Horan JT, Liesveld JL, Fenton P, Blumberg N, Walters MC. Hematopoietic stem cell transplantation for multiply transfused patients with sickle cell disease and thalassemia after low-dose total body irradiation, fludarabine, and rabbit anti-thymocyte globulin. Bone Marrow Transplant. 2005;35:171–7.

    Article  CAS  PubMed  Google Scholar 

  41. Shenoy S, Grossman WJ, DiPersio J, Yu LC, Wilson D. A novel reduced-intensity stem cell transplant regimen for nonmalignant disorders. Bone Marrow Transplant. 2005;35:345–52.

    Article  CAS  PubMed  Google Scholar 

  42. Iannone R, Casella JF, Fuchs EJ, Chen AR, Jones RJ. Results of minimally toxic nonmyeloablative transplantation in patients with sickle cell anemia and beta-thalassemia. Biol Blood Marrow Transplant. 2003;9:519–28.

    Article  PubMed  Google Scholar 

  43. Bhatia M, Sheth S. Hematopoietic stem cell transplantation in sickle cell disease: patient selection and special considerations. J Blood Med. 2015;6:229–38.

    PubMed  PubMed Central  Google Scholar 

  44. Talano JA, Cairo MS. Smoothing the crescent curve: sickle cell disease. Hematol Am Soc Hematol Educ Program. 2014;2014:468–74.

    Article  Google Scholar 

  45. Walters MC, Sullivan KM. Stem-cell transplantation for sickle cell disease. New Engl J Med. 2010;362:955–6.

    Article  CAS  PubMed  Google Scholar 

  46. Vermylen C, Cornu G, Ferster A, Brichard B, Ninane J, et al. Haematopoietic stem cell transplantation for sickle cell anaemia: the first 50 patients transplanted in Belgium. Bone Marrow Transplant. 1998;22:1–6.

    Article  CAS  PubMed  Google Scholar 

  47. Gaziev J, Lucarelli G. Allogeneic cellular gene therapy for hemoglobinopathies. Hematol/Oncol Clin North Am. 2010;24:1145–63.

    Article  Google Scholar 

  48. Vermylen C. Hematopoietic stem cell transplantation in sickle cell disease. Blood Rev. 2003;17:163–6.

    Article  PubMed  Google Scholar 

  49. Lucarelli G, Isgro A, Sodani P, Gaziev J. Hematopoietic stem cell transplantation in thalassemia and sickle cell anemia. Cold Spring Harb Perspect Med. 2012;2:a011825.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Michlitsch JG, Walters MC. Recent advances in bone marrow transplantation in hemoglobinopathies. Curr Mol Med. 2008;8:675–89.

    Article  CAS  PubMed  Google Scholar 

  51. Hladun R, Elorza I, Olive T, Dapena JL, Llort A, Sanchez de Toledo J, Diaz, de Heredia C. Results of hematopoietic stem cell transplantation in hemoglobinopathies: thalassemia major and sickle cell disease. An De Pediatr (Barc, Spain: 2003). 2013;79:75–82.

    Article  CAS  Google Scholar 

  52. Bhatia M, Kolva E, Cimini L, Jin Z, Satwani P, et al. Health-related quality of life after allogeneic hematopoietic stem cell transplantation for sickle cell disease. Biol Blood Marrow Transplant. 2015;21:666–72.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Dallas MH, Triplett B, Shook DR, Hartford C, Srinivasan A. Long-term outcome and evaluation of organ function in pediatric patients undergoing haploidentical and matched related hematopoietic cell transplantation for sickle cell disease. Biol Blood Marrow Transplant. 2013;19:820–30.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Choudhary D, Sharma SK, Gupta N, Kharya G, Pavecha P. Treosulfan-thiotepa-fludarabine-based conditioning regimen for allogeneic transplantation in patients with thalassemia major: a single-center experience from north India. Biol Blood Marrow Transplant. 2013;19:492–5.

    Article  CAS  PubMed  Google Scholar 

  55. Strocchio L, Zecca M, Comoli P, Mina T, Giorgiani G. Treosulfan-based conditioning regimen for allogeneic haematopoietic stem cell transplantation in children with sickle cell disease. Br J Haematol. 2015;169:726–36.

    Article  CAS  PubMed  Google Scholar 

  56. Gluckman E. Allogeneic transplantation strategies including haploidentical transplantation in sickle cell disease. Hematol Am Soc Hematol Educ Program. 2013;2013:370–6.

    Article  Google Scholar 

  57. Badat M, Davies J. Gene therapy in a patient with sickle cell disease. New Engl J Med. 2017;376:2093–4.

    Article  PubMed  Google Scholar 

  58. Locatelli F, Rocha V, Reed W, Bernaudin F, Ertem M, Grafakos S, et al. Related umbilical cord blood transplantation in patients with thalassemia and sickle cell disease. Blood. 2003;101:2137–43.

    Article  CAS  PubMed  Google Scholar 

  59. Walters MC, Sullivan KM, Bernaudin F, Souillet G, Vannier JP, Johnson FL, et al. Neurologic complications after allogeneic marrow transplantation for sickle cell anemia. Blood. 1995;85:879–84.

    CAS  PubMed  Google Scholar 

  60. Gaziev J, Sodani P, Polchi P, Andreani M, Lucarelli G. Bone marrow transplantation in adults with thalassemia: treatment and long-term follow-up. Ann NY Acad Sci. 2005;1054:196–205.

    Article  PubMed  Google Scholar 

  61. Krishnamurti L, Blazar BR, Wagner JE. Bone marrow transplantation without myeloablation for sickle cell disease. New Engl J Med. 2001;344:68.

    Article  CAS  PubMed  Google Scholar 

  62. Bernaudin F, Socie G, Kuentz M, Chevret S, Duval M, et al. Long-term results of related myeloablative stem-cell transplantation to cure sickle cell disease. Blood. 2007;110:2749–56.

    Article  CAS  PubMed  Google Scholar 

  63. Krishnamurti L, Blazar BR, Wagner JE: Bone marrow transplantation without myeloablation for sickle cell disease. The New England journal of medicine 2001;344:68.

    Article  CAS  PubMed  Google Scholar 

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Author contributions

HMA and SKH wrote the manuscript. SY, AK, SMI contributed substantially to the conception, acquisition, analysis, and interpretation of the data for the work. All authors approved the final approval of the version to be published.

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Authors and Affiliations

  1. Department of Internal Medicine, Seton Hall University (St Francis) program, Trenton, USA

    Hafiz Muhammad Aslam

  2. King Faisal University Hospital and Research Center, Riyadh, Saudi Arabia

    Said Yousuf

  3. Department of Medicine, Division of Hematology/Oncology, Vanderbilt University, Nashville, TN, USA

    Adetola Kassim

  4. Department of Internal Medicine, University at Buffalo (Catholic Health System-Sisters of Charity) Program, Buffalo, USA

    Shumaila Muhammad Iqbal

  5. Department of Medicine, Division of Hematology, Mayo Clinic, Rochester, MN, 55905, USA

    Shahrukh K. Hashmi

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  1. Hafiz Muhammad Aslam
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Correspondence to Hafiz Muhammad Aslam.

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Aslam, H.M., Yousuf, S., Kassim, A. et al. Hematopoietic stem cell transplantation for adult sickle cell disease in the era of universal donor availibility. Bone Marrow Transplant 53, 1390–1400 (2018). https://doi.org/10.1038/s41409-018-0193-6

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