Current Problems in Pediatric and Adolescent Health Care
Volume 38, Issue 1 , Pages 6-18 , January 2008

Hematopoietic Cell Transplantation for Hemoglobinopathies

  • Lakshmanan Krishnamurti, MD

      Affiliations

    • Children’s Hospital of Pittsburgh of the University of Pittsburgh Medical Center Health System, Division of Hematology/Oncology/BMT, Pittsburgh, Pennsylvania
    • L.K. and H.F.B. contributed equally to this work.
  • ,
  • H. Franklin Bunn, MD

      Affiliations

    • Hematology Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
    • L.K. and H.F.B. contributed equally to this work.
  • ,
  • Andrea M. Williams, BA

      Affiliations

    • Children’s Hospital of Pittsburgh of the University of Pittsburgh Medical Center Health System, Division of Hematology/Oncology/BMT, Pittsburgh, Pennsylvania
  • ,
  • Jakub Tolar, MD, PhD

      Affiliations

    • Division of Pediatric Hematology, Oncology, Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.

References 

  1. 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
  2. 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
  3. Serjeant GR. Natural history and determinants of clinical severity of sickle cell disease. Curr Opin Hematol. 1995;2:103–108
  4. Platt OS, Thorington BD, Brambilla DJ, Milner PF, Rosse WF, Vichinsky E, et al. Pain in sickle cell disease (Rates and risk factors). N Engl J Med. 1991;325:11–16
  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 [see comments]). N Engl J Med. 1994;330:1639–1644
  6. Ohene-Frempong K. Stroke in sickle cell disease: demographic, clinical, and therapeutic considerations. Semin Hematol. 1991;28:213–219
  7. Armstrong FD, Thompson RJ, Wang W, Zimmerman R, Pegelow CH, Miller S, et al. Cognitive functioning and brain magnetic resonance imaging in children with sickle cell disease (Neuropsychology Committee of the Cooperative Study of Sickle Cell Disease). Pediatrics. 1996;97:864–870
  8. White DA, Moinuddin A, McKinstry RC, Noetzel M, Armstrong M, DeBaun M. Cognitive screening for silent cerebral infarction in children with sickle cell disease. J Pediatr Hematol Oncol. 2006;28:166–169
  9. Miller ST, Macklin EA, Pegelow CH, Kinney TR, Sleeper LA, Bello JA, et al. Silent infarction as a risk factor for overt stroke in children with sickle cell anemia: a report from the Cooperative Study of Sickle Cell Disease. J Pediatr. 2001;139:385–390
  10. 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
  11. 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
  12. Adams RJ. Stroke prevention in sickle cell disease. Curr Opin Hematol. 2000;7:101–105
  13. 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. Blood. 2000;95:1918–1924
  14. 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;22:1–6
  15. 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
  16. 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
  17. Abboud MR, Jackson SM, Barredo J, Beatty J, Laver J. Bone marrow transplantation for sickle cell anemia. Am J Pediatr Hematol Oncol. 1994;16:86–89
  18. Giardini C, Galimberti M, Lucarelli G, Polchi P, Angelucci E, Baronciani D, et al. Bone marrow transplantation in sickle-cell anemia in Pesaro. Bone Marrow Transplant. 1993;12:122–123
  19. 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
  20. Ferster A, Bujan W, Corazza F, Devalck C, Fondu P, Toppet M, et al. Bone marrow transplantation corrects the splenic reticuloendothelial dysfunction in sickle cell anemia. Blood. 1993;81:1102–1105
  21. Eggleston B, Patience M, Edwards S, Adamkiewicz T, Buchanan GR, Davies SC, et al. Effect of myeloablative bone marrow transplantation on growth in children with sickle cell anaemia: results of the multicenter study of haematopoietic cell transplantation for sickle cell anaemia. Br J Haematol. 2007;136:673–676
  22. 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;2:100–104
  23. Chakrabarti S, Bareford D. A survey on patient perception of reduced-intensity transplantation in adults with sickle cell disease. Bone Marrow Transplant. 2007;39:447–451
  24. Kodish E, Lantos J, Siegler M, Kohrman A, Johnson FL. Bone marrow transplantation in sickle cell disease: the trade-off between early mortality and quality of life. Clin Res. 1990;38:694–700
  25. Kodish E, Lantos J, Stocking C, Singer PA, Siegler M, Johnson FL. Bone marrow transplantation for sickle cell disease (A study of parents’ decisions). N Engl J Med. 1991;325:1349–1353
  26. van Besien K, Koshy M, Anderson-Shaw L, Talishy N, Dorn L, Devine S, et al. Allogeneic stem cell transplantation for sickle cell disease (A study of patients’ decisions). Bone Marrow Transplant. 2001;28:545–549
  27. Reed W, Smith R, Dekovic F, Lee JY, Saba JD, Trachtenberg E, et al. Comprehensive banking of sibling donor cord blood for children with malignant and nonmalignant disease. Blood. 2003;101:351–357
  28. Brichard B, Vermylen C, Ninane J, Cornu G. Persistence of fetal hemoglobin production after successful transplantation of cord blood stem cells in a patient with sickle cell anemia. J Pediatr. 1996;128:241–243
  29. Gore L, Lane PA, Quinones RR, Giller RH. Successful cord blood transplantation for sickle cell anemia from a sibling who is human leukocyte antigen-identical: implications for comprehensive care. J Pediatr Hematol Oncol. 2000;22:437–440
  30. 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;101:2137–2143
  31. 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
  32. 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
  33. Adamkiewicz TV, Mehta PS, Boyer MW, Kedar A, Olson TA, Olson E, et al. Transplantation of unrelated placental blood cells in children with high-risk sickle cell disease. Bone Marrow Transplant. 2004;34:405–411
  34. 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 centers experience. Pediatr Transplant. 2007;
  35. Werner E, Yanovich S, Rubinstein P, Kurtzberg J. Unrelated placental cord blood transplantation in a patient with sickle cell disease and acute non-lymphocytic leukemia. Blood. 1997;90:
  36. La Nasa G, Giardini C, Locatelli F, Argiolu F, Vassallo E, Prete A, et al. Unrelated bone marrow transplantation in thalassemia (The experience of the Italian Bone Marrow Transplant Group (GITMO)). Haematologica. 2002;87:58–61
  37. Storb RF, Lucarelli G, McSweeney PA, Childs RW. Hematopoietic cell transplantation for benign hematological disorders and solid tumors. Hematology (Am Soc Hematol Educ Program). 2003;372–397
  38. Krishnamurti L, Blazar BR, Wagner JE. Bone marrow transplantation without myeloablation for sickle cell disease. N Engl J Med. 2001;344:68
  39. Krishnamurti L, Wu CJ, Baker KS, Wagner JE. Matched sibling donor hematopoietic cell transplantation for sickle cell disease using a reduced intensity conditioning regimen can lead to stable long term engraftment. Blood. 2005;106(11):6569;(Abstract #3172)
  40. Schleuning M, Stoetzer O, Waterhouse C, Schlemmer M, Ledderose G, Kolb HJ. Hematopoietic stem cell transplantation after reduced-intensity conditioning as treatment of sickle cell disease. Exp Hematol. 2002;30:7–10
  41. 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
  42. van Besien K, Bartholomew A, Stock W, Peace D, Devine S, Sher D, et al. Fludarabine-based conditioning for allogeneic transplantation in adults with sickle cell disease. Bone Marrow Transplant. 2000;26:445–449
  43. Mazur M, Kurtzberg J, Halperin E, Ciocci G, Szabolcs P. Transplantation of a child with sickle cell anemia with an unrelated cord blood unit after reduced intensity conditioning. J Pediatr Hematol Oncol. 2006;28:840–844
  44. 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;35:171–177
  45. 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;9:519–528
  46. Woolfrey AE, Pulsipher MA, Storb R. Non-myeloablative hematopoietic cell transplant for treatment of nonmalignant disorders in children. Int J Hematol. 2002;76(Suppl 2):271–277
  47. Olivieri NF, Nathan DG, MacMillan JH, Wayne AS, Liu PP, McGee A, et al. Survival in medically treated patients with homozygous beta-thalassemia. N Engl J Med. 1994;331:574–578
  48. Gaziev J, Lucarelli G. Stem cell transplantation and gene therapy for hemoglobinopathies. Curr Hematol Rep. 2005;4:126–131
  49. 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
  50. Olivieri NF, Brittenham GM, McLaren CE, Templeton DM, Cameron RG, McClelland RA, et al. Long-term safety and effectiveness of iron-chelation therapy with deferiprone for thalassemia major. N Engl J Med. 1998;339:417–423
  51. Hoffbrand VA, Wonke B. Long term deferiprone chelation therapy. Adv Exp Med Biol. 2002;509:127–139
  52. Tanner MA, Galanello R, Dessi C, Smith GC, Westwood MA, Agus A, et al. A randomized, placebo-controlled, double-blind trial of the effect of combined therapy with deferoxamine and deferiprone on myocardial iron in thalassemia major using cardiovascular magnetic resonance. Circulation. 2007;115:1876–1884
  53. Cappellini MD, Cohen A, Piga A, Bejaoui M, Perrotta S, Agaoglu L, et al. A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia. Blood. 2006;107:3455–3462
  54. Neufeld EJ. Oral chelators deferasirox and deferiprone for transfusional iron overload in thalassemia major: new data, new questions. Blood. 2006;107:3436–3441
  55. Eldor A, Rachmilewitz EA. The hypercoagulable state in thalassemia. Blood. 2002;99:36–43
  56. Powars DR, Chan LS, Hiti A, Ramicone E, Johnson C. Outcome of sickle cell anemia: a 4-decade observational study of 1056 patients. Medicine (Baltimore). 2005;84:363–376
  57. 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
  58. Machado RF, Martyr S, Kato GJ, Barst RJ, Anthi A, Robinson MR, et al. Sildenafil therapy in patients with sickle cell disease and pulmonary hypertension. Br J Haematol. 2005;130:445–453
  59. Platt OS, Thorington BD, Brambilla DJ, Milner PF, Rosse WF, Vichinsky E, et al. Pain in sickle cell disease: rates and risk factors. N Engl J Med. 1991;325:11–16
  60. Charache S, Barton FB, Moore RD, Terrin ML, Steinberg MH, Dover GJ, et al. Hydroxyurea and sickle cell anemia (Clinical utility of a myelosuppressive “switching” agent. The Multicenter Study of Hydroxyurea in Sickle Cell Anemia). Medicine (Baltimore). 1996;75:300–326
  61. Steinberg MH, Rodgers GP. Pharmacologic modulation of fetal hemoglobin. Medicine (Baltimore). 2001;80:328–344
  62. Rother RP, Bell L, Hillmen P, Gladwin MT. The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: a novel mechanism of human disease. JAMA. 2005;293:1653–1662
  63. 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
  64. Nolan VG, Adewoye A, Baldwin C, Wang L, Ma Q, Wyszynski DF, et al. Sickle cell leg ulcers: associations with haemolysis and SNPs in Klotho (TEK and genes of the TGF-beta/BMP pathway). Br J Haematol. 2006;133:570–578
  65. Driscoll MC, Hurlet A, Styles L, McKie V, Files B, Olivieri N, et al. Stroke risk in siblings with sickle cell anemia. Blood. 2003;101:2401–2404
  66. Hoppe C, Klitz W, Cheng S, Apple R, Steiner L, Robles L, et al. Gene interactions and stroke risk in children with sickle cell anemia. Blood. 2004;103:2391–2396
  67. Sebastiani P, Ramoni MF, Nolan V, Baldwin CT, Steinberg MH. Genetic dissection and prognostic modeling of overt stroke in sickle cell anemia. Nat Genet. 2005;37:435–440
  68. Baldwin C, Nolan VG, Wyszynski DF, Ma QL, Sebastiani P, Embury SH, et al. Association of klotho, bone morphogenic protein 6, and annexin A2 polymorphisms with sickle cell osteonecrosis. Blood. 2005;106:372–375
  69. Haverfield EV, McKenzie CA, Forrester T, Bouzekri N, Harding R, Serjeant G, et al. UGT1A1 variation and gallstone formation in sickle cell disease. Blood. 2005;105:968–972
  70. Weatherall MW, Higgs DR, Weiss H, Weatherall DJ, Serjeant GR. Phenotype/genotype relationships in sickle cell disease: a pilot twin study. Clin Lab Haematol. 2005;27:384–390
  71. Sebastiani P, Nolan VG, Baldwin CT, Abad-Grau MM, Wang L, Adewoye AH, et al. A network model to predict the risk of death in sickle cell disease. Blood. 2007;110:2727–2735
  72. Steinberg MH, Barton F, Castro O, Pegelow CH, Ballas SK, Kutlar A, et al. Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: risks and benefits up to 9 years of treatment. JAMA. 2003;289:1645–1651
  73. Fung EB, Harmatz P, Milet M, Ballas SK, De Castro L, Hagar W, et al. Morbidity and mortality in chronically transfused subjects with thalassemia and sickle cell disease: a report from the multi-center study of iron overload. Am J Hematol. 2007;82:255–265
  74. Vichinsky E, Onyekwere O, Porter J, Swerdlow P, Eckman J, Lane P, et al. A randomised comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease. Br J Haematol. 2007;136:501–508
  75. Gladwin MT, Kato GJ. Cardiopulmonary complications of sickle cell disease: role of nitric oxide and hemolytic anemia. Hematology Am Soc Hematol Educ Program. 2005;51–57
  76. Wong WY, Powars DR. Overt and incomplete (silent) cerebral infarction in sickle cell anemia: diagnosis and management. Hematol Oncol Clin North Am. 2005;19:839–855vi
  77. Donnez J, Dolmans MM, Demylle D, Jadoul P, Pirard C, Squifflet J, et al. Restoration of ovarian function after orthotopic (intraovarian and periovarian) transplantation of cryopreserved ovarian tissue in a woman treated by bone marrow transplantation for sickle cell anaemia: case report. Hum Reprod. 2006;21:183–188
  78. Chang AH, Sadelain M. The genetic engineering of hematopoietic stem cells: the rise of lentiviral vectors, the conundrum of the LTR, and the promise of lineage-restricted vectors. Mol Ther. 2007;15:445–456
  79. Sadelain M, Boulad F, Galanello R, Giardina P, Locatelli F, Maggio A, et al. Therapeutic options for patients with severe beta-thalassemia: the need for globin gene therapy. Hum Gene Ther. 2007;18:1–9
  80. 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
  81. Chang JC, Ye L, Kan YW. Correction of the sickle cell mutation in embryonic stem cells. Proc Natl Acad Sci USA. 2006;103:1036–1040
  82. Sabatino DE, Seidel NE, Aviles-Mendoza GJ, Cline AP, Anderson SM, Gallagher PG, et al. Long-term expression of gamma-globin mRNA in mouse erythrocytes from retrovirus vectors containing the human gamma-globin gene fused to the ankyrin-1 promoter. Proc Natl Acad Sci USA. 2000;97:13294–13299
  83. Sabatino DE, Wong C, Cline AP, Pyle L, Garrett LJ, Gallagher PG, et al. A minimal ankyrin promoter linked to a human gamma-globin gene demonstrates erythroid specific copy number dependent expression with minimal position or enhancer dependence in transgenic mice. J Biol Chem. 2000;275:28549–28554
  84. Frazar TF, Weisbein JL, Anderson SM, Cline AP, Garrett LJ, Felsenfeld G, et al. Variegated expression from the murine band 3 (AE1) promoter in transgenic mice is associated with mRNA transcript initiation at upstream start sites and can be suppressed by the addition of the chicken beta-globin 5′ HS4 insulator element. Mol Cell Biol. 2003;23:4753–4763
  85. Han XD, Lin C, Chang J, Sadelain M, Kan YW. Fetal gene therapy of alpha-thalassemia in a mouse model. Proc Natl Acad Sci USA. 2007;104:9007–9011
  86. May C, Rivella S, Chadburn A, Sadelain M. Successful treatment of murine beta-thalassemia intermedia by transfer of the human beta-globin gene. Blood. 2002;99:1902–1908
  87. Rivella S, May C, Chadburn A, Riviere I, Sadelain M. A novel murine model of Cooley anemia and its rescue by lentiviral-mediated human beta-globin gene transfer. Blood. 2003;101:2932–2939
  88. Persons DA, Allay ER, Sabatino DE, Kelly P, Bodine DM, Nienhuis AW. Functional requirements for phenotypic correction of murine beta-thalassemia: implications for human gene therapy. Blood. 2001;97:3275–3282
  89. Hanawa H, Hargrove PW, Kepes S, Srivastava DK, Nienhuis AW, Persons DA. Extended beta-globin locus control region elements promote consistent therapeutic expression of a gamma-globin lentiviral vector in murine beta-thalassemia. Blood. 2004;104:2281–2290
  90. Cone RD, Weber-Benarous A, Baorto D, Mulligan RC. Regulated expression of a complete human beta-globin gene encoded by a transmissible retrovirus vector. Mol Cell Biol. 1987;7:887–897
  91. Dzierzak EA, Papayannopoulou T, Mulligan RC. Lineage-specific expression of a human beta-globin gene in murine bone marrow transplant recipients reconstituted with retrovirus-transduced stem cells. Nature. 1988;331:35–41
  92. Plavec I, Papayannopoulou T, Maury C, Meyer F. A human beta-globin gene fused to the human beta-globin locus control region is expressed at high levels in erythroid cells of mice engrafted with retrovirus-transduced hematopoietic stem cells. Blood. 1993;81:1384–1392
  93. Gelinas R, Novak U. Retroviral vectors for the beta-globin gene that demonstrate improved titer and expression. Ann NY Acad Sci. 1990;612:427–441
  94. Novak U, Harris EA, Forrester W, Groudine M, Gelinas R. High-level beta-globin expression after retroviral transfer of locus activation region-containing human beta-globin gene derivatives into murine erythroleukemia cells. Proc Natl Acad Sci USA. 1990;87:3386–3390
  95. 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
  96. Rivella S, Callegari JA, May C, Tan CW, Sadelain M. The cHS4 insulator increases the probability of retroviral expression at random chromosomal integration sites. J Virol. 2000;74:4679–4687
  97. Imren S, Payen E, Westerman KA, Pawliuk R, Fabry ME, Eaves CJ, et al. Permanent and panerythroid correction of murine beta thalassemia by multiple lentiviral integration in hematopoietic stem cells. Proc Natl Acad Sci USA. 2002;99:14380–14385
  98. Hacein-Bey-Abina S, Von Kalle C, Schmidt M, McCormack MP, Wulffraat N, Leboulch P, et al. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science. 2003;302:415–419
  99. Suwanmanee T, Sierakowska H, Fucharoen S, Kole R. Repair of a splicing defect in erythroid cells from patients with beta-thalassemia/HbE disorder. Mol Ther. 2002;6:718–726
  100. Suwanmanee T, Sierakowska H, Lacerra G, Svasti S, Kirby S, Walsh CE, et al. Restoration of human beta-globin gene expression in murine and human IVS2-654 thalassemic erythroid cells by free uptake of antisense oligonucleotides. Mol Pharmacol. 2002;62:545–553
  101. Sierakowska H, Sambade MJ, Agrawal S, Kole R. Repair of thalassemic human beta-globin mRNA in mammalian cells by antisense oligonucleotides. Proc Natl Acad Sci USA. 1996;93:12840–12844
  102. Samakoglu S, Lisowski L, Budak-Alpdogan T, Usachenko Y, Acuto S, Di Marzo R, et al. A genetic strategy to treat sickle cell anemia by coregulating globin transgene expression and RNA interference. Nat Biotechnol. 2006;24:89–94
  103. Chang AH, Stephan MT, Sadelain M. Stem cell-derived erythroid cells mediate long-term systemic protein delivery. Nat Biotechnol. 2006;24:1017–1021
  104. Persons DA, Allay ER, Sawai N, Hargrove PW, Brent TP, Hanawa H, et al. Successful treatment of murine beta-thalassemia using in vivo selection of genetically modified, drug-resistant hematopoietic stem cells. Blood. 2003;102:506–513
  105. Persons DA, Allay JA, Bonifacino A, Lu T, Agricola B, Metzger ME, et al. Transient in vivo selection of transduced peripheral blood cells using antifolate drug selection in rhesus macaques that received transplants with hematopoietic stem cells expressing dihydrofolate reductase vectors. Blood. 2004;103:796–803

 This review is the result of a symposium at the meeting of American Society of Pediatric Hematology and Oncology (ASPHO) in May, 2007.

 Supported by: Children’s Cancer Research Fund, Minneapolis, MN.

PII: S1538-5442(07)00087-9

doi: 10.1016/j.cppeds.2007.10.002

Current Problems in Pediatric and Adolescent Health Care
Volume 38, Issue 1 , Pages 6-18 , January 2008