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Hematopoietic Cell Transplantation and Sickle-Cell Disease: An Option for Everyone?

  • Hematology/Oncology (C Cole, Section Editor)
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Abstract

There have been vast improvements in the care of patients with sickle-cell disease (SCD) such that patients are now surviving four times longer today than in the 1970s. This is largely due to improvements in supportive care therapies such as infection prophylaxis, vaccinations, and better pain management strategies. Hematopoietic cell transplantation (HCT) affords patients with SCD the only curative treatment and is usually reserved only for the most symptomatic of patients who have matched sibling donors. As more is learned about the natural progression of this disease, there has been a push toward modifying conditioning regimens to decrease regimen-related toxicities such that all patients with matched sibling donors can be offered this option. In this article, we review the current state of HCT in patients with SCD and the progress that has been made in an attempt to render this treatment as an option for all patients afflicted with this condition.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. McGann PT. Sickle cell anemia: an underappreciated and unaddressed contributor to global childhood mortality. J Pediatr. 2014;165:18–22.

    Article  PubMed  Google Scholar 

  2. Chakravorty S, Williams TN. Sickle cell disease: a neglected chronic disease of increasing global health importance. Arch Dis Child. 2015;100:48–53.

    Article  PubMed Central  PubMed  Google Scholar 

  3. • Shenoy S. Hematopoietic stem-cell transplantation for sickle cell disease: current evidence and opinions. Ther Adv Hematol. 2013;4:335–44. This paper was important in that it helped to highlight the current advances in Stem Cell Transplantation including advances in sibling donor transplants, unrelated transplants, and haploidentical transplants. It also discussed current indications for transplant.

  4. Powars DR, Chan LS, Hiti A, Ramicone E, Johnson C. Outcome of sickle cell anemia: a 4-decade observational study of 1056 patients. Medicine. 2005;84:363–76.

    Article  PubMed  Google Scholar 

  5. • Yawn BP, Buchanan GR, Afenyi-Annan AN, et al. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. Jama. 2014;312:1033–48. This paper focused on the treatment options for Sickle Cell Disease focusing primarily on medical treatments without mentioning Stem Cell Transplant as a viable option, highlighting the need to improve awareness of this therapeutic modality.

  6. Platt OS, Brambilla DJ, Rosse WF, et al. Mortality in sickle cell disease. Life expectancy and risk factors for early death. N Engl J Med. 1994;330:1639–44.

    Article  CAS  PubMed  Google Scholar 

  7. Quinn CT, Rogers ZR, McCavit TL, Buchanan GR. Improved survival of children and adolescents with sickle cell disease. Blood. 2010;115:3447–52.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Elmariah H, Garrett ME, De Castro LM, et al. Factors associated with survival in a contemporary adult sickle cell disease cohort. Am J Hematol. 2014;89:530–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Kinney TR, Helms RW, O’Branski EE, et al. Safety of hydroxyurea in children with sickle cell anemia: results of the HUG-KIDS study, a phase I/II trial. Pediatric Hydroxyurea Group. Blood. 1999;94:1550–4.

    CAS  PubMed  Google Scholar 

  10. Adams RJ, McKie VC, Hsu L, et al. Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial doppler ultrasonography. New Engl J Med. 1998;339:5–11.

    Article  CAS  PubMed  Google Scholar 

  11. Charache S, Terrin ML, Moore RD, et al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. New Engl J Med. 1995;332:1317–22.

    Article  CAS  PubMed  Google Scholar 

  12. Alvarez O, Yovetich NA, Scott JP, et al. Pain and other non-neurological adverse events in children with sickle cell anemia and previous stroke who received hydroxyurea and phlebotomy or chronic transfusions and chelation: results from the SWiTCH clinical trial. Am J Hematol. 2013;88:932–8.

    Article  CAS  PubMed  Google Scholar 

  13. Johnson FL, Look AT, Gockerman J, Ruggiero MR, Dalla-Pozza L, Billings FT 3rd. Bone-marrow transplantation in a patient with sickle-cell anemia. New Engl J Med. 1984;311:780–3.

    Article  CAS  PubMed  Google Scholar 

  14. Bernaudin F, Sfgm TC. Stem cell transplantation in sickle cell disease: results, perspectives. Arch Pediatr. 2008;15:633–5.

    Article  PubMed  Google Scholar 

  15. Panepinto JA, Walters MC, Carreras J, 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 

  16. Hoppe CC, Walters MC. Bone marrow transplantation in sickle cell anemia. Curr Opin Oncol. 2001;13:85–90.

    Article  CAS  PubMed  Google Scholar 

  17. Walters MC, Storb R, Patience M, 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;95:1918–24.

    CAS  PubMed  Google Scholar 

  18. Vermylen C, Cornu G, Ferster A, 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 

  19. Quinn CT, Lee NJ, Shull EP, Ahmad N, Rogers ZR, Buchanan GR. Prediction of adverse outcomes in children with sickle cell anemia: a study of the Dallas Newborn Cohort. Blood. 2008;111:544–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Walters MC, Patience M, Leisenring W, et al. Bone marrow transplantation for sickle cell disease. New Engl J Med. 1996;335:369–76.

    Article  CAS  PubMed  Google Scholar 

  21. Walters MC, Patience M, Leisenring W, et al. Stable mixed hematopoietic chimerism after bone marrow transplantation for sickle cell anemia. Biol Blood Marrow Transplant. 2001;7:665–73.

    Article  CAS  PubMed  Google Scholar 

  22. 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 

  23. Iannone R, Casella JF, Fuchs EJ, et al. 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 

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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Krishnamurti L, Kharbanda S, Biernacki MA, et al. Stable long-term donor engraftment following reduced-intensity hematopoietic cell transplantation for sickle cell disease. Biol Blood Marrow Transplant. 2008;14:1270–8.

    Article  PubMed  Google Scholar 

  26. Bhatia M, Jin Z, Baker C, et al. Reduced toxicity, myeloablative conditioning with BU, fludarabine, alemtuzumab and SCT from sibling donors in children with sickle cell disease. Bone Marrow Transplant. 2014;49:913–20.

    Article  CAS  PubMed  Google Scholar 

  27. Matthes-Martin S, Lawitschka A, Fritsch G, et al. Stem cell transplantation after reduced-intensity conditioning for sickle cell disease. Eur J Haematol. 2013;90:308–12.

    Article  PubMed  Google Scholar 

  28. • Gluckman E. Allogeneic transplantation strategies including haploidentical transplantation in sickle cell disease. Hematol Am Soc Hematol Educ Program. 2013;2013:370–6. Reviewed the novelty of haploidentical stem cell transplantation and its utility in Sickle Cell Disease, highlighting outcomes. One of the first papers highlighting this treatment route.

  29. Locatelli F, Rocha V, Reed W, 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 

  30. Boncimino A, Bertaina A, Locatelli F. Cord blood transplantation in patients with hemoglobinopathies. Transfus Apher Sci. 2010;42:277–81.

    Article  PubMed  Google Scholar 

  31. Bolanos-Meade J, Brodsky RA. Blood and marrow transplantation for sickle cell disease: is less more? Blood Rev. 2014;28:243–8.

    Article  PubMed  Google Scholar 

  32. • Kamani NR, Walters MC, Carter 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;18:1265–72. Highlighted the multi-center trial evaluating the role of unrelated cord blood transplants in patients with sickle cell disease.

  33. Adamkiewicz TV, Szabolcs P, Haight A, et al. Unrelated cord blood transplantation in children with sickle cell disease: review of four-center experience. Pediatr Transplant. 2007;11:641–4.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed Central  PubMed  Google Scholar 

  35. • Radhakrishnan K, Bhatia M, Geyer MB, et al. Busulfan, fludarabine, and alemtuzumab conditioning and unrelated cord blood transplantation in children with sickle cell disease. Biol Blood Marrow Transplant. 2013;19:676–7. Highlighted the multi-center trial evaluating the role of unrelated cord blood transplants in patients with sickle cell disease.

  36. Gragert L, Eapen M, Williams E, 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 

  37. Munchel AT, Kasamon YL, Fuchs EJ. Treatment of hematological malignancies with nonmyeloablative, HLA-haploidentical bone marrow transplantation and high dose, post-transplantation cyclophosphamide. Best Pract Res Clin Haematol. 2011;24:359–68.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Brodsky RA, Luznik L, Bolanos-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;42:523–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. • Bolanos-Meade J, Fuchs EJ, Luznik L, 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. As with the reference above, the paper reviewed haploidentical Stem Cell Transplantation in this patient population with a newer modality of using post transplant cyclophosphamide and its efficacy.

  40. • Dallas MH, Triplett B, Shook DR, et al. 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. Contrasted the above paper in that the approach was using a CD34 selected approach rather than post transplant cyclophosphamide and focused on long terms outcomes after transplant in these patients.

  41. Verlinsky Y, Rechitsky S, Schoolcraft W, Strom C, Kuliev A. Preimplantation diagnosis for Fanconi anemia combined with HLA matching. JAMA. 2001;285:3130–3.

    Article  CAS  PubMed  Google Scholar 

  42. • Kahraman S, Beyazyurek C, Yesilipek MA, et al. Successful haematopoietic stem cell transplantation in 44 children from healthy siblings conceived after preimplantation HLA matching. Reprod Biomed Online. 2014;29:340–51. Reviewed the efficacy of pre-implantation HLA matching in patients undergoing HCT.

  43. Morgan ER, Girod J, Rinehart JS. Having a child to save a sibling: reassessing risks and benefits of creating stem cell donors. Pediatr Blood Cancer. 2007;48:249–53.

    Article  PubMed  Google Scholar 

  44. Romero Z, Urbinati F, Geiger S, et al. β-Globin gene transfer to human bone marrow for sickle cell disease. J Clin Invest. 2013;pii:67930.

    Google Scholar 

  45. Platt OS, Guinan EC. Bone marrow transplantation in sickle cell anemia–the dilemma of choice. New Engl J Med. 1996;335:426–8.

    Article  CAS  PubMed  Google Scholar 

  46. Nickel RS, Hendrickson JE, Haight AE. The ethics of a proposed study of hematopoietic stem cell transplant for children with “less severe” sickle cell disease. Blood. 2014;124:861–6.

    Article  CAS  PubMed  Google Scholar 

  47. Walters MC, Hardy K, Edwards S, et al. Pulmonary, gonadal, and central nervous system status after bone marrow transplantation for sickle cell disease. Biol Blood Marrow Transplant. 2010;16:263–72.

    Article  PubMed Central  PubMed  Google Scholar 

  48. Bhatia M, Walters MC. Hematopoietic cell transplantation for thalassemia and sickle cell disease: past, present and future. Bone Marrow Transplant. 2008;41:109–17.

    Article  CAS  PubMed  Google Scholar 

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Author notes

    Authors and Affiliations

    1. Division of Pediatric Hematology/Oncology/Stem Cell Transplantation, Columbia University Medical Center, Morgan Stanley Children’s Hospital of New York, 161 Fort Washington Avenue, IP-7, New York, NY, 10032, USA

      Justine Kahn

    2. Division of Pediatric Stem Cell Transplantation, Columbia University Medical Center, Morgan Stanley Children’s Hospital of New York, 3959 Broadway, CHN 1016, New York, NY, 10032, USA

      Elana Smilow

    3. Division of Pediatric Stem Cell Transplantation, Columbia University Medical Center, 3959 Broadway, CHN 1007, New York, NY, 10032, USA

      Monica Bhatia

    Authors
    1. Justine Kahn
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    2. Elana Smilow
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    3. Monica Bhatia
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    Corresponding author

    Correspondence to Monica Bhatia.

    Additional information

    Justine Kahn and Elana Smilow contributed equally to this work and should both be considered first authors.

    This article is part of the Topical Collection on Hematology/Oncology.

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    Kahn, J., Smilow, E. & Bhatia, M. Hematopoietic Cell Transplantation and Sickle-Cell Disease: An Option for Everyone?. Curr Pediatr Rep 3, 146–153 (2015). https://doi.org/10.1007/s40124-015-0079-7

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    • DOI: https://doi.org/10.1007/s40124-015-0079-7

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