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Allogeneic cellular and autologous stem cell therapy for sickle cell disease: ‘whom, when and how’

Bone Marrow Transplantation volume 47, pages 1489–1498 (2012)Cite this article

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Abstract

Sickle cell disease (SCD) is an autosomal recessive inherited hematological disorder characterized by chronic hemolysis and vaso-occlusion, resulting in multiorgan dysfunction and premature death. The only known curative therapy for patients with severe SCD is myeloablative conditioning and allo-SCT from HLA-matched sibling donors. In this state of the art review, we discuss current and future considerations including patient selection/eligibility, intensity of conditioning regimens, allogeneic graft sources, graft manipulation, mixed donor chimerism, organ function and stability and autologous gene correction stem cell strategies. Recent novel approaches to promote mixed donor chimerism have included the use of matched unrelated adult donors, umbilical cord blood donors, haploidentical familial donors and the utilization of nonmyeloablative, such as reduced intensity and reduced toxicity conditioning regimens. Future strategies will include gene therapy and autologous gene correction stem cell designs. Prospects are bright for novel stem and cellular approaches for patients with severe SCD, and we are currently at the end of the beginning for utilizing cellular therapeutics for the curative treatment of this chronic and debilitating condition.

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References

  1. Modell B, Darlison M . Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ 2008; 86: 480–487.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Weatherall DJ . The inherited diseases of hemoglobin are an emerging global health burden. Blood 2010; 115: 4331–4336.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Bunn HF . Pathogenesis and treatment of sickle cell disease. N Engl J Med 1997; 337: 762–769.

    CAS  PubMed  Google Scholar 

  4. Steinberg MH . Management of sickle cell disease. N Engl J Med 1999; 340: 1021–1030.

    CAS  PubMed  Google Scholar 

  5. Platt OS, Brambilla DJ, Rosse WF, Milner PF, Castro O, Steinberg MH et al. Mortality in sickle cell disease. Life expectancy and risk factors for early death. N Engl J Med 1994; 330: 1639–1644.

    CAS  PubMed  Google Scholar 

  6. Battersby AJ, Knox-Macaulay HH, Carrol ED . Susceptibility to invasive bacterial infections in children with sickle cell disease. Pediatr Blood Cancer 2010; 55: 401–406.

    PubMed  Google Scholar 

  7. DeCeulaer K, Wilson WA, Morgan AG, Serjeant GR . Plasma haemoglobin and complement activation in sickle cell disease. J Clin Lab Immunol 1981; 6: 57–60.

    CAS  PubMed  Google Scholar 

  8. Janoff E, Rubins J . Invasive pneumococcal disease in the immunocompromised host. In: Tomasz A (ed). Streptococcus pneumnoniae. Mary Ann Liebert: New York, 2000.

    Google Scholar 

  9. Koffi KG, Sawadogo D, Meite M, Nanho DC, Tanoh ES, Attia AK et al. Reduced levels of T-cell subsets CD4+ and CD8+ in homozygous sickle cell anaemia patients with splenic defects. Hematol J 2003; 4: 363–365.

    PubMed  Google Scholar 

  10. Musa BO, Onyemelukwe GC, Hambolu JO, Mamman AI, Isa AH . Pattern of serum cytokine expression and T-cell subsets in sickle cell disease patients in vaso-occlusive crisis. Clin Vaccine Immunol 2010; 17: 602–608.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Pearson HA, Gallagher D, Chilcote R, Sullivan E, Wilimas J, Espeland M et al. Developmental pattern of splenic dysfunction in sickle cell disorders. Pediatrics 1985; 76: 392–397.

    CAS  PubMed  Google Scholar 

  12. William BM, Corazza GR . Hyposplenism: a comprehensive review. Part I: basic concepts and causes. Hematology 2007; 12: 1–13.

    PubMed  Google Scholar 

  13. Herrick JB . Peculiar elongated and sickle-shaped red blood corpuscles in a case of severe anemia. Arch Intern Med 1910; 6: 517–521.

    Google Scholar 

  14. Orkin SH, Higgs DR . Medicine. Sickle cell disease at 100 years. Science 2010; 329: 291–292.

    CAS  PubMed  Google Scholar 

  15. Platt OS, Brambilla DJ, Rosse WF, Milner PF, Castro O, Steinberg MH et al. Mortality in sickle cell disease. Life expectancy and risk factors for early death. N Engl J Med 1994; 330: 1639–1644.

    CAS  PubMed  Google Scholar 

  16. Leikin SL, Gallagher D, Kinney TR, Sloane D, Klug P, Rida W . Mortality in children and adolescents with sickle cell disease. Cooperative study of sickle cell disease. Pediatrics 1989; 84: 500–508.

    CAS  PubMed  Google Scholar 

  17. Miller ST, Sleeper LA, Pegelow CH, Enos LE, Wang WC, Weiner SJ et al. Prediction of adverse outcomes in children with sickle cell disease. N Engl J Med 2000; 342: 83–89.

    CAS  PubMed  Google Scholar 

  18. Ohene-Frempong K, Weiner SJ, Sleeper LA, Miller ST, Embury S, Moohr JW et al. Cerebrovascular accidents in sickle cell disease: rates and risk factors. Blood 1998; 91: 288–294.

    CAS  PubMed  Google Scholar 

  19. Charache S, Dover GJ, Moore RD, Eckert S, Ballas SK, Koshy M et al. Hydroxyurea: effects on hemoglobin F production in patients with sickle cell anemia. Blood 1992; 79: 2555–2565.

    CAS  PubMed  Google Scholar 

  20. Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert SV 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. N Engl J Med 1995; 332: 1317–1322.

    CAS  PubMed  Google Scholar 

  21. Kinney TR, Helms RW, O′Branski EE, Ohene-Frempong K, Wang W, Daeschner C 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: 1550–1554.

    CAS  PubMed  Google Scholar 

  22. Wang WC, Wynn LW, Rogers ZR, Scott JP, Lane PA, Ware RE . A two-year pilot trial of hydroxyurea in very young children with sickle-cell anemia. J Pediatr 2001; 139: 790–796.

    CAS  PubMed  Google Scholar 

  23. Roman E, Cooney E, Harrison L, Militano O, Wolownik K, Hawks R et al. Preliminary results of the safety of immunotherapy with gemtuzumab ozogamicin following reduced intensity allogeneic stem cell transplant in children with CD33+ acute myeloid leukemia. Clin Cancer Res 2005; 11 (19 Pt 2): 7164s–7170s.

    CAS  PubMed  Google Scholar 

  24. de Montalembert M, Davies SC . Is hydroxyurea leukemogenic in children with sickle cell disease? Blood 2001; 98: 2878–2879.

    CAS  PubMed  Google Scholar 

  25. Moschovi M, Psychou F, Menegas D, Tsangaris GT, Tzortzatou-Stathopoulou F, Nicolaidou P . Hodgkin′s disease in a child with sickle cell disease treated with hydroxyurea. Pediatr Hematol Oncol 2001; 18: 371–376.

    CAS  PubMed  Google Scholar 

  26. Stricker RB, Linker CA, Crowley TJ, Embury SH . Hematologic malignancy in sickle cell disease: report of four cases and review of the literature. Am J Hematol 1986; 21: 223–230.

    CAS  PubMed  Google Scholar 

  27. Johnson FL, Look AT, Gockerman J, Ruggiero MR, Dalla-Pozza L, Billings 3rd FT . Bone-marrow transplantation in a patient with sickle-cell anemia. N Engl J Med 1984; 311: 780–783.

    CAS  PubMed  Google Scholar 

  28. 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: 369–376.

    CAS  PubMed  Google Scholar 

  29. Panepinto JA, Walters MC, Carreras J, Marsh J, Bredeson CN, Gale RP 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: 479–485.

    PubMed  Google Scholar 

  30. 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: 2749–2756.

    CAS  PubMed  Google Scholar 

  31. Hsu LL, Champion HC, Campbell-Lee SA, Bivalacqua TJ, Manci EA, Diwan BA et al. Hemolysis in sickle cell mice causes pulmonary hypertension due to global impairment in nitric oxide bioavailability. Blood 2007; 109: 3088–3098.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. 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: 1918–1924.

    CAS  PubMed  Google Scholar 

  33. Hernigou P, Bernaudin F, Reinert P, Kuentz M, Vernant JP . Bone-marrow transplantation in sickle-cell disease. Effect on osteonecrosis: a case report with a four-year follow-up. J Bone Joint Surg Am 1997; 79: 1726–1730.

    CAS  PubMed  Google Scholar 

  34. May C, Rivella S, Callegari J, Heller G, Gaensler KM, Luzzatto L et al. Therapeutic haemoglobin synthesis in beta-thalassaemic mice expressing lentivirus-encoded human beta-globin. Nature 2000; 406: 82–86.

    CAS  PubMed  Google Scholar 

  35. Persons DA . Hematopoietic stem cell gene transfer for the treatment of hemoglobin disorders. Hematol Am Soc Hematol Educ Program 2009; 1: 690–697.

    Google Scholar 

  36. Steen RG, Helton KJ, Horwitz EM, Benaim E, Thompson S, Bowman LC et al. Improved cerebrovascular patency following therapy in patients with sickle cell disease: initial results in 4 patients who received HLA-identical hematopoietic stem cell allografts. Ann Neurol 2001; 49: 222–229.

    CAS  PubMed  Google Scholar 

  37. Walters MC . Sickle cell anemia and hematopoietic cell transplantation: when is a pound of cure worth more than an ounce of prevention? Pediatr Transplant 2004; 8 Suppl 5: 33–38.

    PubMed  Google Scholar 

  38. Steen RG, Emudianughe T, Hankins GM, Wynn LW, Wang WC, Xiong X et al. Brain imaging findings in pediatric patients with sickle cell disease. Radiology 2003; 228: 216–225.

    PubMed  Google Scholar 

  39. Kalinyak KA, Morris C, Ball WS, Ris MD, Harris R, Rucknagel D . Bone marrow transplantation in a young child with sickle cell anemia. Am J Hematol 1995; 48: 256–261.

    CAS  PubMed  Google Scholar 

  40. Bunn HF . Pathogenesis and treatment of sickle cell disease. N Engl J Med 1997; 337: 762–769.

    CAS  PubMed  Google Scholar 

  41. Cairo MS, Rocha V, Gluckman E, Hale G, Wagner J . Alternative allogeneic donor sources for transplantation for childhood diseases: unrelated cord blood and haploidentical family donors. Biol Blood Marrow Transplant 2008; 14 (1 suppl): 44–53.

    PubMed  Google Scholar 

  42. Kurtzberg J, Laughlin M, Graham ML, Smith C, Olson JF, Halperin EC et al. Placental blood as a source of hematopoietic stem cells for transplantation into unrelated recipients. N Engl J Med 1996; 335: 157–166.

    CAS  PubMed  Google Scholar 

  43. Liao Y, Geyer MB, Yang AJ, Cairo MS . Cord blood transplantation and stem cell regenerative potential. Exp Hematol 2011; 39: 393–412.

    PubMed  Google Scholar 

  44. 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: 641–644.

    CAS  PubMed  Google Scholar 

  45. Bhatia M, Baldinger L, Billote G, Morris E, Bradley M, George D et al. Preliminary results of non-ablative conditioning (NAC) with busulfan (Bu), fludarabine (Flu) and alemtuzumab followed by allogeneic stem cell transplantation (AlloSCT) to induce mixed donor chimerism in patients with sickle cell disease (SCD). Biol Blood Marrow Transplantation 2008; 14 (2 suppl): 82–83.

    Google Scholar 

  46. European Group for Blood and Marrow Transplantation. Survey of outcomes of unrelated cord blood transplant in patients with hemoglobinopathies: a retrospective study on behalf of CIBMTR, NYCB and EUROCORD. Mons, Belgium, 2010.

  47. Ruggeri A, Eapen M, Scaravadou A, Cairo MS, Bhatia M, Kurtzberg J et al. Umbilical cord blood transplantation for children with thalassemia and sickle cell disease. Biol Blood Marrow Transplant 2011; 17: 1375–1382.

    PubMed  PubMed Central  Google Scholar 

  48. Bernardo ME, Zecca M, Piras E, Vacca A, Giorgiani G, Cugno C et al. Treosulfan-based conditioning regimen for allogeneic haematopoietic stem cell transplantation in patients with thalassaemia major. Br J Haematol 2008; 143: 548–551.

    PubMed  Google Scholar 

  49. Lucarelli G, Clift RA, Galimberti M, Polchi P, Angelucci E, Baronciani D et al. Marrow transplantation for patients with thalassemia: results in class 3 patients. Blood 1996; 87: 2082–2088.

    CAS  PubMed  Google Scholar 

  50. Sodani P, Isgro A, Gaziev J, Polchi P, Paciaroni K, Marziali M et al. Purified T-depleted, CD34+ peripheral blood and bone marrow cell transplantation from haploidentical mother to child with thalassemia. Blood 2010; 115: 1296–1302.

    CAS  PubMed  Google Scholar 

  51. Friedman DF, Lukas MB, Jawad A, Larson PJ, Ohene-Frempong K, Manno CS . Alloimmunization to platelets in heavily transfused patients with sickle cell disease. Blood 1996; 88: 3216–3222.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  53. Zimring JC, Hair GA, Deshpande SS, Horan JT . Immunization to minor histocompatibility antigens on transfused RBCs through crosspriming into recipient MHC class I pathways. Blood 2006; 107: 187–189.

    CAS  PubMed  Google Scholar 

  54. Socie G, Salooja N, Cohen A, Rovelli A, Carreras E, Locasciulli A et al. Nonmalignant late effects after allogeneic stem cell transplantation. Blood 2003; 101: 3373–3385.

    CAS  PubMed  Google Scholar 

  55. Vassal G, Deroussent A, Hartmann O, Challine D, Benhamou E, Valteau-Couanet D et al. Dose-dependent neurotoxicity of high-dose busulfan in children: a clinical and pharmacological study. Cancer Res 1990; 50: 6203–6207.

    CAS  PubMed  Google Scholar 

  56. Pulsipher MA, Boucher KM, Wall D, Frangoul H, Duval M, Goyal RK et al. Reduced-intensity allogeneic transplantation in pediatric patients ineligible for myeloablative therapy: results of the pediatric blood and narrow transplant consortium study ONC0313. Blood 2009; 114: 1429–1436.

    CAS  PubMed  Google Scholar 

  57. Del Toro G, Satwani P, Harrison L, Cheung YK, Brigid Bradley M, George D et al. A pilot study of reduced intensity conditioning and allogeneic stem cell transplantation from unrelated cord blood and matched family donors in children and adolescent recipients. Bone Marrow Transplant 2004; 33: 613–622.

    CAS  PubMed  Google Scholar 

  58. Satwani P, Harrison L, Morris E, Del Toro G, Cairo MS . Reduced-intensity allogeneic stem cell transplantation in adults and children with malignant and nonmalignant diseases: end of the beginning and future challenges. Biol Blood Marrow Transplant 2005; 11: 403–422.

    PubMed  Google Scholar 

  59. Bradley MB, Satwani P, Baldinger L, Morris E, van de Ven C, Del Toro G et al. Reduced intensity allogeneic umbilical cord blood transplantation in children and adolescent recipients with malignant and non-malignant diseases. Bone Marrow Transplant 2007; 40: 621–631.

    CAS  PubMed  Google Scholar 

  60. Walters MC, Patience M, Leisenring W, Rogers ZR, Aquino VM, Buchanan GR et al. Stable mixed hematopoietic chimerism after bone marrow transplantation for sickle cell anemia. Biol Blood Marrow Transplant 2001; 7: 665–673.

    CAS  PubMed  Google Scholar 

  61. Andreani M, Testi M, Gaziev J, Condello R, Bontadini A, Tazzari PL et al. Quantitatively different red cell/nucleated cell chimerism in patients with long-term, persistent hematopoietic mixed chimerism after bone marrow transplantation for thalassemia major or sickle cell disease. Haematologica 2011; 96: 128–133.

    PubMed  Google Scholar 

  62. Krishnamurti L, Kharbanda S, Biernacki MA, Zhang W, Baker KS, Wagner JE et al. Stable long-term donor engraftment following reduced-intensity hematopoietic cell transplantation for sickle cell disease. Biol Blood Marrow Transplant 2008; 14: 1270–1278.

    PubMed  Google Scholar 

  63. Chakraverty R, Peggs K, Chopra R, Milligan DW, Kottaridis PD, Verfuerth S et al. Limiting transplantation-related mortality following unrelated donor stem cell transplantation by using a nonmyeloablative conditioning regimen. Blood 2002; 99: 1071–1078.

    CAS  PubMed  Google Scholar 

  64. Shenoy S, Grossman WJ, DiPersio J, Yu LC, Wilson D, Barnes YJ et al. A novel reduced-intensity stem cell transplant regimen for nonmalignant disorders. Bone Marrow Transplant 2005; 35: 345–352.

    CAS  PubMed  Google Scholar 

  65. Bhatia M, Geyer MB, Baker C, Zuckerman WA, Duffy D, Satwani P et al. Long term organ stability and outcome in children and adolescents with sickle cell disease (SCD) following reduced toxicity conditioning (RTC) allogeneic stem cell transplantation (SCT). Biol Blood Marrow Transplant 2011; 17: S180–S181.

    Google Scholar 

  66. 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: 2309–2317.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Bolanos-Meade J, Lanzkron S, Kemberling H, Gamper C, Ambinder RF, Luznik L et al. Nonmyeloablative HLA-haploidentical bone marrow transplantation (haplo-BMT) with post-transplant high-dose cyclophosphamide (Cy) in patients with severe hemoglobinopathies. Biol Blood Marrow Transplant 2011, 17–S285.

  68. Aversa F, Tabilio A, Terenzi A, Velardi A, Falzetti F, Giannoni C et al. Successful engraftment of T-cell-depleted haploidentical “three-loci” incompatible transplants in leukemia patients by addition of recombinant human granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells to bone marrow inoculum. Blood 1994; 84: 3948–3955.

    CAS  PubMed  Google Scholar 

  69. Bhatia M, Walters MC . Hematopoietic cell transplantation for thalassemia and sickle cell disease: past, present and future. Bone Marrow Transplant 2008; 41: 109–117.

    CAS  PubMed  Google Scholar 

  70. Aversa F, Tabilio A, Velardi A, Cunningham I, Terenzi A, Falzetti F et al. Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. N Engl J Med 1998; 339: 1186–1193.

    CAS  PubMed  Google Scholar 

  71. 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: 3447–3454.

    PubMed  Google Scholar 

  72. Evans PC, Lambert N, Maloney S, Furst DE, Moore JM, Nelson JL . Long-term fetal microchimerism in peripheral blood mononuclear cell subsets in healthy women and women with scleroderma. Blood 1999; 93: 2033–2037.

    CAS  PubMed  Google Scholar 

  73. van Rood JJ, Loberiza Jr FR, Zhang MJ, Oudshoorn M, Claas F, Cairo MS et al. Effect of tolerance to noninherited maternal antigens on the occurrence of graft-versus-host disease after bone marrow transplantation from a parent or an HLA-haploidentical sibling. Blood 2002; 99: 1572–1577.

    PubMed  Google Scholar 

  74. Bank A, Dorazio R, Leboulch P . A phase I/II clinical trial of beta-globin gene therapy for beta-thalassemia. Ann N Y Acad Sci 2005; 1054: 308–316.

    CAS  PubMed  Google Scholar 

  75. Sadelain M, Boulad F, Lisowki L, Moi P, Riviere I . Stem cell engineering for the treatment of severe hemoglobinopathies. Curr Mol Med 2008; 8: 690–697.

    CAS  PubMed  Google Scholar 

  76. Lisowski L, Sadelain M . Current status of globin gene therapy for the treatment of beta-thalassaemia. Br J Haematol 2008; 141: 335–345.

    CAS  PubMed  Google Scholar 

  77. Townes TM . Gene replacement therapy for sickle cell disease and other blood disorders. Hematol Am Soc Hematol Educ Program 2008; 1: 193–196.

    Google Scholar 

  78. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS et al. Embryonic stem cell lines derived from human blastocysts. Science 1998; 282: 1145–1147.

    CAS  PubMed  Google Scholar 

  79. Takahashi K, Yamanaka S . Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126: 663–676.

    CAS  PubMed  Google Scholar 

  80. Teo AK, Vallier L . Emerging use of stem cells in regenerative medicine. Biochem J 2010; 428: 11–23.

    CAS  PubMed  Google Scholar 

  81. Warren L, Manos PD, Ahfeldt T, Loh YH, Li H, Lau F et al. Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell 2010; 7: 618–630.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Kaufman DS . Toward clinical therapies using hematopoietic cells derived from human pluripotent stem cells. Blood 2009; 114: 3513–3523.

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Wu LC, Sun CW, Ryan TM, Pawlik KM, Ren J, Townes TM . Correction of sickle cell disease by homologous recombination in embryonic stem cells. Blood 2006; 108: 1183–1188.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Hanna J, Wernig M, Markoulaki S, Sun CW, Meissner A, Cassady JP et al. Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science 2007; 318: 1920–1923.

    CAS  PubMed  Google Scholar 

  85. Management of therapy of sickle cell disease. In: Institute NHLaB (ed), Division of Blood Diseases and Resources, 3rd edn Bethesda, MD, December 1995, pp NIH publication no. 95–2117.

  86. Buchanan GR, Smith SJ . Pneumococcal septicemia despite pneumococcal vaccine and prescription of penicillin prophylaxis in children with sickle cell anemia. Am J Dis Child 1986; 140: 428–432.

    CAS  PubMed  Google Scholar 

  87. Falletta JM, Woods GM, Verter JI, Buchanan GR, Pegelow CH, Iyer RV et al. Discontinuing penicillin prophylaxis in children with sickle cell anemia. Prophylactic Penicillin Study II. J Pediatr 1995; 127: 685–690.

    CAS  PubMed  Google Scholar 

  88. Gaston MH, Verter JI, Woods G, Pegelow C, Kelleher J, Presbury G et al. Prophylaxis with oral penicillin in children with sickle cell anemia. A randomized trial. N Engl J Med 1986; 314: 1593–1599.

    CAS  PubMed  Google Scholar 

  89. Halasa NB, Shankar SM, Talbot TR, Arbogast PG, Mitchel EF, Wang WC et al. Incidence of invasive pneumococcal disease among individuals with sickle cell disease before and after the introduction of the pneumococcal conjugate vaccine. Clin Infect Dis 2007; 44: 1428–1433.

    CAS  PubMed  Google Scholar 

  90. Adams RJ, McKie VC, Hsu L, Files B, Vichinsky E, Pegelow C et al. Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. N Engl J Med 1998; 339: 5–11.

    CAS  PubMed  Google Scholar 

  91. Embury S, Hebbel RP, Mohandas N, Steinberg MH (eds). Sickle cell disease: basic principles and clinical practice. Raven Press: New York, 1994.

    Google Scholar 

  92. Vichinsky EP, Earles A, Johnson RA, Hoag MS, Williams A, Lubin B . Alloimmunization in sickle cell anemia and transfusion of racially unmatched blood. N Engl J Med 1990; 322: 1617–1621.

    CAS  PubMed  Google Scholar 

  93. Field JJ, DeBaun MR, Yan Y, Strunk RC . Growth of lung function in children with sickle cell anemia. Pediatr Pulmonol 2008; 43: 1061–1066.

    PubMed  Google Scholar 

  94. Field JJ, Glassberg J, Gilmore A, Howard J, Patankar S, Yan Y et al. Longitudinal analysis of pulmonary function in adults with sickle cell disease. Am J Hematol 2008; 83: 574–576.

    PubMed  PubMed Central  Google Scholar 

  95. Klings ES, Wyszynski DF, Nolan VG, Steinberg MH . Abnormal pulmonary function in adults with sickle cell anemia. Am J Respir Crit Care Med 2006; 173: 1264–1269.

    PubMed  PubMed Central  Google Scholar 

  96. Koumbourlis AC, Lee DJ, Lee A . Longitudinal changes in lung function and somatic growth in children with sickle cell disease. Pediatr Pulmonol 2007; 42: 483–488.

    PubMed  Google Scholar 

  97. MacLean JE, Atenafu E, Kirby-Allen M, MacLusky IB, Stephens D, Grasemann H et al. Longitudinal decline in lung volume in a population of children with sickle cell disease. Am J Respir Crit Care Med 2008; 178: 1055–1059.

    PubMed  Google Scholar 

  98. Ataga KI, Sood N, De Gent G, Kelly E, Henderson AG, Jones S et al. Pulmonary hypertension in sickle cell disease. Am J Med 2004; 117: 665–669.

    PubMed  Google Scholar 

  99. Castro O, Hoque M, Brown BD . Pulmonary hypertension in sickle cell disease: cardiac catheterization results and survival. Blood 2003; 101: 1257–1261.

    CAS  PubMed  Google Scholar 

  100. Connor P, Veys P, Amrolia P, Haworth S, Ashworth M, Moledina S . Pulmonary hypertension in children with Evans syndrome. Pediatr Hematol Oncol 2008; 25: 93–98.

    PubMed  Google Scholar 

  101. Gladwin MT, Sachdev V, Jison ML, Shizukuda Y, Plehn JF, Minter K et al. Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med 2004; 350: 886–895.

    CAS  PubMed  Google Scholar 

  102. Kato GJ, McGowan V, Machado RF, Little JA, Taylor JT, Morris CR et al. Lactate dehydrogenase as a biomarker of hemolysis-associated nitric oxide resistance, priapism, leg ulceration, pulmonary hypertension, and death in patients with sickle cell disease. Blood 2006; 107: 2279–2285.

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Machado RF, Gladwin MT . Chronic sickle cell lung disease: new insights into the diagnosis, pathogenesis and treatment of pulmonary hypertension. Br J Haematol 2005; 129: 449–464.

    CAS  PubMed  Google Scholar 

  104. Morris CR, Kato GJ, Poljakovic M, Wang X, Blackwelder WC, Sachdev V et al. Dysregulated arginine metabolism, hemolysis-associated pulmonary hypertension, and mortality in sickle cell disease. JAMA 2005; 294: 81–90.

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank Erin Morris, RN, for her outstanding contribution to the preparation of this manuscript, and to all the brave children and adults with SCD who suffer from this chronic condition.

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Authors and Affiliations

  1. Department of Pediatrics, Hackensack University Medical Center, Hackensack, NJ, USA

    J Freed

  2. Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA

    J Talano

  3. Department of Pediatrics, Columbia University, New York, NY, USA

    T Small & A Ricci

  4. Department of Pediatrics, Medicine, Pathology, Microbiology and Immunology, Cell Biology and Anatomy, New York Medical College, Valhalla, NY, USA

    M S Cairo

  5. These authors contributed equally to this work,

    J Freed & J Talano

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Correspondence to M S Cairo.

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This manuscript has been supported in part by a grant from the Pediatric Cancer Research Foundation.

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Freed, J., Talano, J., Small, T. et al. Allogeneic cellular and autologous stem cell therapy for sickle cell disease: ‘whom, when and how’. Bone Marrow Transplant 47, 1489–1498 (2012). https://doi.org/10.1038/bmt.2011.245

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