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Review

An update review of new therapies in sickle cell disease: the prospects for drug combinations

, , , &
Pages 157-170 | Received 19 Dec 2023, Accepted 07 Feb 2024, Published online: 04 Mar 2024

References

  • Piel FB, Steinberg MH, Rees DC, et al. Sickle cell disease. N Engl J Med. 2017;376(16):1561–1573. doi: 10.1056/NEJMra1510865
  • Esham KS, Rodday AM, Smith HP, et al. Assessment of health-related quality of life among adults hospitalized with sickle cell disease vaso-occlusive crisis. Blood Adv. 2020;4(1):19–27. doi: 10.1182/bloodadvances.2019000128
  • Piel FB, Rees DC, DeBaun MR, et al. Defining global strategies to improve outcomes in sickle cell disease: a lancet haematology commission. Lancet Haematol. 2023;10(8):e633–e686. doi: 10.1016/S2352-3026(23)00096-0
  • Chou ST, Alsawas M, Fasano RM, et al. American society of hematology 2020 guidelines for sickle cell disease: transfusion support. Blood Adv. 2020;4(2):327–355. doi: 10.1182/bloodadvances.2019001143
  • Ataga KI. The challenge of clinical end points in sickle cell disease. Blood. 2023;142(24):2047–2054. doi: 10.1182/blood.2023021220
  • Ali MA, Ahmad A, Chaudry H, et al. Efficacy and safety of recently approved drugs for sickle cell disease: a review of clinical trials. Exp Hematol. 2020;92:11–18. doi: 10.1016/j.exphem.2020.08.008
  • Salinas Cisneros G, Thein SL. Research in sickle cell disease: from bedside to bench to bedside. Hemasphere. 2021;5(6):e584. doi: 10.1097/HS9.0000000000000584
  • Tshilolo L, Tomlinson G, Williams TN, et al. Hydroxyurea for children with sickle cell anemia in Sub-Saharan Africa. N Engl J Med. 2019;380(2):121–131. doi: 10.1056/NEJMoa1813598
  • Opoka RO, Ndugwa CM, Latham TS, et al. Novel use of hydroxyurea in an African region with malaria (NOHARM): a trial for children with sickle cell anemia. Blood. 2017;130(24):2585–2593. doi: 10.1182/blood-2017-06-788935
  • John CC, Opoka RO, Latham TS, et al. Hydroxyurea Dose Escalation for Sickle Cell Anemia in Sub-Saharan Africa. N Engl J Med. 2020;382(26):2524–2533. doi: 10.1056/NEJMoa2000146
  • 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(11):932–938. doi: 10.1002/ajh.23547
  • Ware R, Schultz W, Yovetich N, et al. Stroke with transfusions changing to hydroxyurea (SWiTCH): a phase III randomized clinical trial for treatment of children with sickle cell anemia, stroke, and iron overload. Pediatr Blood Cancer. 2011;57(6):1011–1017. doi: 10.1002/pbc.23145
  • Ware RE, Helms RW. SWITCH investigators. Stroke with transfusions changing to hydroxyurea (SWiTCH). Blood. 2012;119(17):3925–3932. doi: 10.1182/blood-2011-11-392340
  • Ware RE, Davis BR, Schultz WH, et al. Hydroxycarbamide versus chronic transfusion for maintenance of transcranial doppler flow velocities in children with sickle cell anaemia—TCD with transfusions changing to hydroxyurea (TWiTCH): a multicentre, open-label, phase 3, non-inferiority trial. Lancet. 2016;387(10019):661–670. doi: 10.1016/S0140-6736(15)01041-7
  • Galadanci NA, Umar Abdullahi S, Vance LD, et al. Feasibility trial for primary stroke prevention in children with sickle cell anemia in Nigeria (SPIN trial). Am J Hematol. 2017;92(8):780–788. doi: 10.1002/ajh.24770
  • Galadanci NA, Abdullahi SU, Ali Abubakar S, et al. Moderate fixed-dose hydroxyurea for primary prevention of strokes in Nigerian children with sickle cell disease: final results of the SPIN trial. Am J Hematol. 2020;95(9):E247–E250. doi: 10.1002/ajh.25900
  • Abdullahi SU, Jibir BW, Bello-Manga H, et al. Hydroxyurea for primary stroke prevention in children with sickle cell anaemia in Nigeria (SPRING): a double-blind, multicentre, randomised, phase 3 trial. Lancet Haematol. 2022;9(1):e26–e37. doi: 10.1016/S2352-3026(21)00368-9
  • Ambrose EE, Latham TS, Songoro P, et al. Hydroxyurea with dose escalation for primary stroke risk reduction in children with sickle cell anaemia in Tanzania (SPHERE): an open-label, phase 2 trial. Lancet Haematol. 2023;10(4):e261–e271. doi: 10.1016/S2352-3026(22)00405-7
  • Hankins JS, Mccarville MB, Rankine-Mullings A, et al. Prevention of conversion to abnormal transcranial doppler with hydroxyurea in sickle cell anemia: a phase III international randomized clinical trial. Am J Hematol. 2015;90(12):1099–1105. doi: 10.1002/ajh.24198
  • Nieves RM, Latham T, Marte N, et al. Hydroxyurea with dose escalation to reduce primary stroke risk in children with sickle cell anemia in Dominican Republic: the sacred trial. Blood. 2022;140(Supplement 1):451–452. doi: 10.1182/blood-2022-168324
  • Rankine-Mullings A, Reid M, Soares D, et al. Hydroxycarbamide treatment reduces transcranial doppler velocity in the absence of transfusion support in children with sickle cell anaemia, elevated transcranial doppler velocity, and cerebral vasculopathy: the EXTEND trial. Br J Haematol. 2021;195(4):612–620. doi: 10.1111/bjh.17698
  • Molokie R, Lavelle D, Gowhari M, et al. Oral tetrahydrouridine and decitabine for non-cytotoxic epigenetic gene regulation in sickle cell disease: a randomized phase 1 study. PLoS Med. 2017;14(9):e1002382. doi: 10.1371/journal.pmed.1002382
  • Andemariam B, Højlund Nielsen P, Zillmer R, et al. ASCENT1: a phase 2 trial to evaluate the efficacy and safety of oral decitabine-tetrahydrouridine (NDec) in patients with sickle cell disease. Blood. 2022;140(Supplement 1):5420–5421. doi: 10.1182/blood-2022-169283
  • Cao H, Stamatoyannopoulos G, Jung M. Induction of human γ globin gene expression by histone deacetylase inhibitors. Blood. 2004;103(2):701–709. doi: 10.1182/blood-2003-02-0478
  • McCaffrey PG, Newsome DA, Fibach E, et al. Induction of γ-globin by histone deacetylase inhibitors. Blood. 1997;90(5):2075–2083. doi: 10.1182/blood.V90.5.2075
  • Perrine S, Ginder G, Faller D, et al. A short-term trial of butyrate to stimulate fetal-globin-gene expression in the β-globin disorders. N Engl J Med. 1993;328(2):81–86. doi: 10.1056/NEJM199301143280202
  • Selby R, Nisbet-Brown E, Basran R, et al. Valproic acid and augmentation of fetal hemoglobin in individuals with and without sickle cell disease. Blood. 1997;90(2):891–893. doi: 10.1182/blood.V90.2.891
  • Kutlar A, Reid ME, Inati A, et al. A dose-escalation phase IIa study of 2,2-dimethylbutyrate (HQK-1001), an oral fetal globin inducer, in sickle cell disease. Am J Hematol. 2013;88(11):E255–E260. doi: 10.1002/ajh.23533
  • Okam M, Esrick E, Mandell E, et al. Phase 1/2 trial of vorinostat in patients with sickle cell disease who have not benefitted from hydroxyurea. Blood. 2015;125(23):3668–3669. doi: 10.1182/blood-2015-03-635391
  • Study details | study of panobinostat (LBH589) in patients with sickle cell disease | ClinicalTrials.Gov [Internet]. [cited 2023 Dec 4]. Available from: https://clinicaltrials.gov/study/NCT01245179
  • McArthur JG, Svenstrup N, Chen C, et al. A novel, highly potent and selective phosphodiesterase-9 inhibitor for the treatment of sickle cell disease. Haematologica. 2020;105(3):623–631. doi: 10.3324/haematol.2018.213462
  • Andemariam B, Bronte L, Gordeuk V, et al. The safety, pharmacokinetics & pharmacodynamic effects of IMR-687, a highly-selective PDE9 inhibitor, in adults with sickle cell disease: phase-2A placebo-controlled & open-label extension studies. Hemasphere. 2021;5:90.
  • Oder E, Safo MK, Abdulmalik O, et al. New developments in anti-sickling agents: can drugs directly prevent the polymerization of sickle haemoglobin in vivo? Br J Haematol Med. 2016;175:24–30.
  • Hutchaleelaha A, Patel M, Washington C, et al. Pharmacokinetics and pharmacodynamics of voxelotor (GBT440) in healthy adults and patients with sickle cell disease. Br J Clin Pharmacol. 2019;85(6):1290–1302. doi: 10.1111/bcp.13896
  • Vichinsky E, Hoppe CC, Ataga KI, et al. A phase 3 randomized trial of voxelotor in sickle cell disease. N Engl J Med. 2019;381(6):509–519. doi: 10.1056/NEJMoa1903212
  • Howard J, Ataga K, Brown R, et al. Voxelotor in adolescents and adults with sickle cell disease (HOPE): long-term follow-up results of an international, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Haematol. 2021;8(5):e323–e333. doi: 10.1016/S2352-3026(21)00059-4
  • Estepp JH, Kalpatthi R, Woods G, et al. Safety and efficacy of voxelotor in pediatric patients with sickle cell disease aged 4 to 11 years. Pediatr Blood Cancer. 2022;69(8):e29716. doi: 10.1002/pbc.29716
  • Saraf SL, Abdullahi SU, Akinsete AM, et al. Preliminary results from a multicenter phase 2/3 study of next-generation HbS polymerization inhibitor GBT021601 for the treatment of patients with sickle cell disease. Blood. 2023;142(Supplement 1):274. doi: 10.1182/blood-2023-177781
  • Ataga KI, Kutlar A, Kanter J, et al. Crizanlizumab for the prevention of pain crises in sickle cell disease. N Engl J Med. 2017;376(5):429–439. doi: 10.1056/NEJMoa1611770
  • Liles DK, Shah NR, Scullin B, et al. Long-term biological effects in sickle cell disease: insights from a post-crizanlizumab study. Br J Haematol. 2021;195(4):e150–e153. doi: 10.1111/bjh.17739
  • Kutlar A, Kanter J, Liles DK, et al. Effect of crizanlizumab on pain crises in subgroups of patients with sickle cell disease: a SUSTAIN study analysis. Am J Hematol. 2019;94(1):55–61. doi: 10.1002/ajh.25308
  • Telen MJ, Wun T, McCavit TL, et al. Randomized phase 2 study of GMI-1070 in SCD: reduction in time to resolution of vaso-occlusive events and decreased opioid use. Blood. 2015;125(17):2656–2664. doi: 10.1182/blood-2014-06-583351
  • Dampier CD, Telen MJ, Wun T, et al. A randomized clinical trial of the efficacy and safety of rivipansel for sickle cell vaso-occlusive crisis. Blood. 2023;141(2):168–179. doi: 10.1182/blood.2022015797
  • Biemond B, Tombak A, Kilinc Y, et al. Sevuparin for the treatment of acute pain crisis in patients with sickle cell disease: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Haematol. 2021;8(5):e334–e343. doi: 10.1016/S2352-3026(21)00053-3
  • Dansdill D, Halandras PM, Beverly J, et al. Synthetic, organic compound vepoloxamer (P-188) potentiates tissue plasminogen activator. J Vasc Surg. 2018;67(1):294–299. doi: 10.1016/j.jvs.2016.03.473
  • Adams-Graves P, Kedar A, Koshy M, et al. RheothRx (poloxamer 188) injection for the acute painful episode of sickle cell disease: a pilot study. Blood. 1997;90(5):2041–2046. doi: 10.1182/blood.V90.5.2041
  • Orringer EP, Casella JF, Ataga KI, et al. Purified poloxamer 188 for treatment of acute vaso-occlusive crisis of sickle cell disease: a randomized controlled trial. JAMA. 2001;286(17):2099–2106. doi: 10.1001/jama.286.17.2099
  • Casella J, Barton B, Kanter J, et al. Effect of poloxamer 188 vs placebo on painful vaso-occlusive episodes in children and adults with sickle cell disease: a randomized clinical trial. JAMA. 2021;325(15):1513–1523. doi: 10.1001/jama.2021.3414
  • Niihara Y, Miller ST, Kanter J, et al. A phase 3 trial of l -glutamine in sickle cell disease. N Engl J Med. 2018;379(3):226–235. doi: 10.1056/NEJMoa1715971
  • Zaidi AU, Estepp J, Shah N, et al. A reanalysis of pain crises data from the pivotal L-glutamine in sickle cell disease trial. Contemp Clin Trials. 2021;110:106546. doi: 10.1016/j.cct.2021.106546
  • Morris SM, Jr. Recent advances in arginine metabolism: roles and regulation of the arginases. Br J Pharmacol. 2000;157(6) :922–930. doi: 10.1111/j.1476-5381.2009.00278.x
  • Morris CR, Kuypers FA, Lavrisha L, et al. A randomized, placebo-controlled trial of arginine therapy for the treatment of children with sickle cell disease hospitalized with vaso-occlusive pain episodes. Haematologica. 2013;98(9):1375–1382. doi: 10.3324/haematol.2013.086637
  • Morris CR, Brown LAS, Reynolds M, et al. Impact of arginine therapy on mitochondrial function in children with sickle cell disease during vaso-occlusive pain. Blood. 2020;136(12):1402–1406. doi: 10.1182/blood.2019003672
  • Onalo R, Cooper P, Cilliers A, et al. Randomized control trial of oral arginine therapy for children with sickle cell anemia hospitalized for pain in Nigeria. Am J Hematol. 2021;96(1):89–97. doi: 10.1002/ajh.26028
  • Dumas G, Habibi A, Onimus T, et al. Eculizumab salvage therapy for delayed hemolysis transfusion reaction in sickle cell disease patients. Blood. 2016;127(8):1062–1064. doi: 10.1182/blood-2015-09-669770
  • McNamara LA, Topaz N, Wang X, et al. High risk for invasive meningococcal disease among patients receiving eculizumab (soliris) despite receipt of meningococcal vaccine. MMWR Morb Mortal Wkly Rep. 2017;66(27):734–737. doi: 10.15585/mmwr.mm6627e1
  • Chonat S, Graciaa S, Shin HS, et al. Eculizumab for complement mediated thrombotic microangiopathy in sickle cell disease. Haematologica. 2020;105(12):2887–2891. doi: 10.3324/haematol.2020.262006
  • Azul M, Shah S, Williams S, et al. Evidence for complement-mediated bone marrow necrosis in a young adult with sickle cell disease. Blood Cells Mol Dis United States. 2021;86:102508. doi: 10.1016/j.bcmd.2020.102508
  • Callaghan M, Ataga K, De Franceschi L, et al. P120: trial in progress: the randomized, double-blind, placebo-controlled phase 2A crosswalk-c trial evaluating the efficacy of crovalimab as adjunct treatment in the prevention of Vaso-Occlusive Episodes (VOES) in Patients (PTS) with Sickle Cell Disease (SCD). Hemasphere. 2022;6:27–28. doi: 10.1097/01.HS9.0000821572.78026.e4
  • Xu JZ, Conrey A, Frey I, et al. A phase 1 dose escalation study of the pyruvate kinase activator mitapivat (AG-348) in sickle cell disease. Blood. 2022;140(19):2053–2062. doi: 10.1182/blood.2022015403
  • van Dijk MJ, Rab MAE, van Oirschot BA, et al. Safety and efficacy of mitapivat, an oral pyruvate kinase activator, in sickle cell disease: a phase 2, open-label study. Am J Hematol. 2022;97(7):E226–E229. doi: 10.1002/ajh.26554
  • Study details | a study evaluating the efficacy and safety of mitapivat (AG-348) in participants with sickle cell disease (RISE UP) | ClinicalTrials.Gov [Internet]. [cited 2023 Dec 10]. Available from: https://clinicaltrials.gov/study/NCT05031780
  • Forsyth S, Schroeder P, Geib J, et al. Safety, pharmacokinetics, and pharmacodynamics of etavopivat (FT-4202), an allosteric activator of pyruvate kinase-R, in healthy adults: a randomized, placebo-controlled, double-blind, first-in-human phase 1 trial. Clin Pharmacol Drug Dev. 2022;11(5):654–665. doi: 10.1002/cpdd.1058
  • Study details | a study of Etavopivat in adults and adolescents with sickle cell disease (HIBISCUS) | ClinicalTrials.Gov [Internet]. [cited 2023 Dec 10]. Available from: https://www.clinicaltrials.gov/study/NCT04624659
  • Iqbal M, Reljic T, Corbacioglu S, et al. Systematic review/Meta-analysis on efficacy of allogeneic hematopoietic cell transplantation in sickle cell disease: an international effort on behalf of the pediatric diseases working party of European society for blood and marrow transplantation and th. Transplant Cell Ther. 2021;27(2):.e167.1–.e167.12. doi: 10.1016/j.jtct.2020.10.007
  • Bhatia M, Kolva E, Cimini L, et al. Health-related quality of life after allogeneic hematopoietic stem cell transplantation for sickle cell disease. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2015;21(4):666–672. doi: 10.1016/j.bbmt.2014.12.007
  • Dedeken L, Lê PQ, Azzi N, et al. Haematopoietic stem cell transplantation for severe sickle cell disease in childhood: a single centre experience of 50 patients. Br J Haematol. 2014;165(3):402–408. doi: 10.1111/bjh.12737
  • Hsieh MM, Kang EM, Fitzhugh CD, et al. Allogeneic hematopoietic stem-cell transplantation for sickle cell disease. N Engl J Med. 2009;361(24):2309–2317. doi: 10.1056/NEJMoa0904971
  • Hulbert ML, Shenoy S. Hematopoietic stem cell transplantation for sickle cell disease: progress and challenges. Pediatr Blood Cancer. 2018;65(9):e27263. doi: 10.1002/pbc.27263
  • King AA, Kamani N, Bunin N, et al. Successful matched sibling donor marrow transplantation following reduced intensity conditioning in children with hemoglobinopathies. Am J Hematol. 2015;90(12):1093–1098. doi: 10.1002/ajh.24183
  • Locatelli F, Kabbara N, Ruggeri A, et al. Outcome of patients with hemoglobinopathies given either cord blood or bone marrow transplantation from an HLA-identical sibling. Blood. 2013;122(6):1072–1078. doi: 10.1182/blood-2013-03-489112
  • Saraf SL, Oh AL, Patel PR, et al. Nonmyeloablative stem cell transplantation with Alemtuzumab/Low-dose irradiation to cure and improve the quality of life of adults with sickle cell disease. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2016;22(3):441–448. doi: 10.1016/j.bbmt.2015.08.036
  • Guilcher GMT, Truong TH, Saraf SL, et al. Curative therapies: allogeneic hematopoietic cell transplantation from matched related donors using myeloablative, reduced intensity, and nonmyeloablative conditioning in sickle cell disease. Semin Hematol. 2018;55(2):87–93. doi: 10.1053/j.seminhematol.2018.04.011
  • Abraham A, Hsieh M, Eapen M, et al. Relationship between mixed donor–recipient chimerism and disease recurrence after hematopoietic cell transplantation for sickle cell disease. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2017;23(12):2178–2183. doi: 10.1016/j.bbmt.2017.08.038
  • 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):1–6. doi: 10.1038/sj.bmt.1701291
  • 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(7):913–920. doi: 10.1038/bmt.2014.84
  • Abraham A, Cluster A, Jacobsohn D, et al. Unrelated umbilical cord blood transplantation for sickle cell disease following reduced-intensity conditioning: results of a phase I trial. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2017;23(9):1587–1592. doi: 10.1016/j.bbmt.2017.05.027
  • Shenoy S, Eapen M, Panepinto JA, et al. A trial of unrelated donor marrow transplantation for children with severe sickle cell disease. Blood. 2016;128(21):2561–2567. doi: 10.1182/blood-2016-05-715870
  • Foell J, Schulte JH, Pfirstinger B, et al. Haploidentical CD3 or α/β T-cell depleted HSCT in advanced stage sickle cell disease. Bone Marrow Transplant. 2019;54(11):1859–1867. doi: 10.1038/s41409-019-0550-0
  • Gaziev J, Isgrò A, Mozzi AF, et al. New insights into the pharmacokinetics of intravenous busulfan in children with sickle cell anemia undergoing bone marrow transplantation. Pediatr Blood Cancer. 2015;62(4):680–686. doi: 10.1002/pbc.25376
  • Limerick E, Abraham A. Across the myeloablative spectrum: hematopoietic cell transplant conditioning regimens for pediatric patients with sickle cell disease. J Clin Med. 2022;11(13):11. doi: 10.3390/jcm11133856
  • Vallée T, Schmid I, Gloning L, et al. Excellent outcome of stem cell transplantation for sickle cell disease. Ann Hematol. 2023;102(11):3217–3227. doi: 10.1007/s00277-023-05447-4
  • de la Fuente J, Dhedin N, Koyama T, et al. Haploidentical bone marrow transplantation with post-transplantation cyclophosphamide plus thiotepa improves donor engraftment in patients with sickle cell anemia: results of an international learning collaborative. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2019;25(6):1197–1209. doi: 10.1016/j.bbmt.2018.11.027
  • Shenoy S. Umbilical cord blood: an evolving stem cell source for sickle cell disease transplants. Stem Cells Transl Med. 2013;2(5):337–340. doi: 10.5966/sctm.2012-0180
  • Bernaudin F, Dalle JH, Bories D, et al. Long-term event-free survival, chimerism and fertility outcomes in 234 patients with sickle-cell anemia younger than 30 years after myeloablative conditioning and matched-sibling transplantation in France. Haematologica. 2020;105(1):91–101. doi: 10.3324/haematol.2018.213207
  • Thomson AM, McHugh TA, Oron AP. Global, regional, and national prevalence and mortality burden of sickle cell disease, 2000–2021: a systematic analysis from the global burden of disease study 2021. Lancet Haematol. 2023;10(8):e585–e599. doi: 10.1016/S2352-3026(23)00118-7
  • Inam Z, Tisdale JF, Leonard A. Outcomes and long-term effects of hematopoietic stem cell transplant in sickle cell disease. Expert Rev Hematol. 2023;16(11):879–903. doi: 10.1080/17474086.2023.2268271
  • Lidonnici MR, Scaramuzza S, Ferrari G. Gene therapy for hemoglobinopathies. Hum Gene Ther. 2023;34(17–18):793–807. doi: 10.1089/hum.2023.138
  • Frangoul H, Locatelli F, Bhatia M, et al. Efficacy and safety of a single dose of exagamglogene autotemcel for severe sickle cell disease. Blood. 2022;140(Supplement 1):29–31. doi: 10.1182/blood-2022-162353
  • Kanter J, Thompson AA, Pierciey FJJ, et al. Lovo-cel gene therapy for sickle cell disease: treatment process evolution and outcomes in the initial groups of the HGB-206 study. Am J Hematol. 2023;98(1):11–22. doi: 10.1002/ajh.26741
  • Kanter J, Walters MC, Krishnamurti L, et al. Biologic and clinical efficacy of LentiGlobin for sickle cell disease. N Engl J Med. 2022;386(7):617–628. doi: 10.1056/NEJMoa2117175
  • Spencer Chapman M, Cull AH, Ciuculescu MF, et al. Clonal selection of hematopoietic stem cells after gene therapy for sickle cell disease. Nat Med. 2023;29(12):3175–3183. doi: 10.1038/s41591-023-02636-6
  • Goyal S, Tisdale J, Schmidt M, et al. Acute myeloid leukemia case after gene therapy for sickle cell disease. N Engl J Med. 2022;386(2):138–147. doi: 10.1056/NEJMoa2109167
  • Lubeck D, Agodoa I, Bhakta N, et al. Estimated life expectancy and income of patients with sickle cell disease compared with those without sickle cell disease. JAMA Netw Open. 2019;2(11):e1915374. doi: 10.1001/jamanetworkopen.2019.15374
  • Jeste ND, Sánchez LM, Urcuyo GS, et al. Stroke avoidance for children in República Dominicana (SACRED): protocol for a prospective study of stroke risk and hydroxyurea treatment in sickle cell anemia. JMIR Res Protoc. 2017;6(6):e107. doi: 10.2196/resprot.7491
  • Study details | study of two doses of crizanlizumab versus placebo in adolescent and adult sickle cell disease patients | ClinicalTrials.Gov [Internet]. [cited 2023 Dec 10]. Available from: https://www.clinicaltrials.gov/study/NCT03814746
  • Andemariam B, Mant T, Eleftheriou P, et al. Treatment with IMR-687, a highly selective PDE9 inhibitor, increases HbF and reduces VOCs in adults with sickle cell disease in a long-term, phase 2a, open-label extension study. Blood. 2021;138(Supplement 1):2046. doi: 10.1182/blood-2021-149536
  • Lucarelli G, Isgrò A, Sodani P, et al. Hematopoietic SCT for the black African and non-black African variants of sickle cell anemia. Bone Marrow Transplant. 2014;49(11):1376–1381. doi: 10.1038/bmt.2014.167
  • Hsieh MM, Fitzhugh CD, Weitzel RP, et al. Nonmyeloablative HLA-matched sibling allogeneic hematopoietic stem cell transplantation for severe sickle cell phenotype. JAMA. 2014;312(1):48–56. doi: 10.1001/jama.2014.7192
  • Ozdogu H, Boga C, Yeral M, et al. Allogenic peripheral stem cell transplantation from HLA-matched related donors for adult sickle cell disease: remarkable outcomes from a single-center trial. Bone Marrow Transplant. 2018;53(7):880–890. doi: 10.1038/s41409-018-0111-y
  • Ozdogu H, Boga C, Yeral M, et al. Excellent outcomes of allogeneic transplantation from peripheral blood of HLA-matched related donors for adult sickle cell disease with ATLG and posttransplant cyclophosphamide-containing regimen: an update work. Bone Marrow Transplant England. 2020;55(8):1647–1651. doi: 10.1038/s41409-020-0805-9
  • Ballas S.K. The evolving pharmacotherapeutic landscape for the treatment of Sickle Cell Disease. Mediterr J Hematol Infect Dis. 2020;12(1):e2020010.

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