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REVIEW

Managing the Cerebrovascular Complications of Sickle Cell Disease: Current Perspectives

, , &
Pages 279-293 | Received 23 Nov 2022, Accepted 31 Mar 2023, Published online: 14 Apr 2023

References

  • Allison AC. Notes on sickle-cell polymorphism. Ann Hum Genet. 1954;19(1):39–51. doi:10.1111/j.1469-1809.1954.tb01261.x
  • Piel FB, Patil AP, Howes RE, et al. Global distribution of the sickle cell gene and geographical confirmation of the malaria hypothesis. Nat Commun. 2010;1:104. doi:10.1038/ncomms1104
  • Esoh K, Wonkam A. Evolutionary history of sickle-cell mutation: implications for global genetic medicine. Hum Mol Genet. 2021;30(R1):R119–R128. doi:10.1093/hmg/ddab004
  • Wailoo K. Drawing Blood: Technology and Disease Identity in Twentieth-Century America. Johns Hopkins University Press; 1999.
  • Steinberg MH. Pathophysiology of sickle cell disease. Baillieres Clin Haematol. 1998;11(1):163–184. doi:10.1016/s0950-3536(98)80074-7
  • Carden MA, Fasano RM, Meier ER. Not all red cells sickle the same: contributions of the reticulocyte to disease pathology in sickle cell anemia. Blood Rev. 2020;40:100637. doi:10.1016/j.blre.2019.100637
  • Hebbel RP. Ischemia-reperfusion injury in sickle cell anemia: relationship to acute chest syndrome, endothelial dysfunction, arterial vasculopathy, and inflammatory pain. Hematol Oncol Clin North Am. 2014;28(2):181–198. doi:10.1016/j.hoc.2013.11.005
  • Kuypers FA. Hemoglobin s polymerization and red cell membrane changes. Hematol Oncol Clin North Am. 2014;28(2):155–179. doi:10.1016/j.hoc.2013.12.002
  • Nouraie M, Lee JS, Zhang Y, et al. The relationship between the severity of hemolysis, clinical manifestations and risk of death in 415 patients with sickle cell anemia in the US and Europe. Haematologica. 2013;98(3):464–472. doi:10.3324/haematol.2012.068965
  • Liguoro I, Arigliani M, Tan HL, Gupta A. The burden of sleep disordered breathing in children with sickle cell disease. Pediatr Pulmonol. 2021;56(12):3607–3633. doi:10.1002/ppul.25632
  • Tantawy A, El-Sherif N, Makkeyah S, et al. Sleep disordered breathing and its relation to stroke and pulmonary hypertension in children with sickle cell disease: a single-center cross-sectional study. Ann Hematol. 2023;102(2):271–281. doi:10.1007/s00277-023-05099-4
  • Vingert B, Tamagne M, Habibi A, et al. Phenotypic differences of CD4(+) T cells in response to red blood cell immunization in transfused sickle cell disease patients. Eur J Immunol. 2015;45(6):1868–1879. doi:10.1002/eji.201445187
  • van Beers EJ, Yang Y, Raghavachari N, et al. Iron, inflammation, and early death in adults with sickle cell disease. Circ Res. 2015;116(2):298–306. doi:10.1161/CIRCRESAHA.116.304577
  • Hoppe CC. Inflammatory mediators of endothelial injury in sickle cell disease. Hematol Oncol Clin North Am. 2014;28(2):265–286. doi:10.1016/j.hoc.2013.11.006
  • Kutlar A, Embury SH. Cellular adhesion and the endothelium: p-selectin. Hematol Oncol Clin North Am. 2014;28(2):323–339. doi:10.1016/j.hoc.2013.11.007
  • Piccin A, Murphy C, Eakins E, et al. Circulating microparticles, protein C, free protein S and endothelial vascular markers in children with sickle cell anaemia. J Extracell Vesicles. 2015;4:28414. doi:10.3402/jev.v4.28414
  • Piccin A, Murphy C, Eakins E, et al. Insight into the complex pathophysiology of sickle cell anaemia and possible treatment. Eur J Haematol. 2019;102(4):319–330. doi:10.1111/ejh.13212
  • Lim MY, Ataga KI, Key NS. Hemostatic abnormalities in sickle cell disease. Curr Opin Hematol. 2013;20(5):472–477. doi:10.1097/MOH.0b013e328363442f
  • Ataga KI, Key NS. Hypercoagulability in sickle cell disease: new approaches to an old problem. Hematology. 2007;2007(1):91–96. doi:10.1182/asheducation-2007.1.91
  • Runge A, Brazel D, Pakbaz Z. Stroke in sickle cell disease and the promise of recent disease modifying agents. J Neurol Sci. 2022;442:120412. doi:10.1016/j.jns.2022.120412
  • Ohene-Frempong K, Weiner SJ, Sleeper LA, et al. Cerebrovascular accidents in sickle cell disease: rates and risk factors. Blood. 1998;91(1):288–294.
  • Maduakor C, Alakbarzade V, Sammaraiee Y, et al. The epidemiology of neurological complications in adults with sickle cell disease: a retrospective cohort study. Front Neurol. 2021;12:744118. doi:10.3389/fneur.2021.744118
  • DeBaun MR, Jordan LC, King AA, et al. American Society of Hematology 2020 guidelines for sickle cell disease: prevention, diagnosis, and treatment of cerebrovascular disease in children and adults. Blood Adv. 2020;4(8):1554–1588. doi:10.1182/bloodadvances.2019001142
  • Adams R, McKie V, Nichols F, et al. The use of transcranial ultrasonography to predict stroke in sickle cell disease. N Engl J Med. 1992;326(9):605–610. doi:10.1056/NEJM199202273260905
  • Kwiatkowski JL, Voeks JH, Kanter J, et al. Ischemic stroke in children and young adults with sickle cell disease in the post-STOP era. Am J Hematol. 2019;94(12):1335–1343. doi:10.1002/ajh.25635
  • Stotesbury H, Kawadler JM, Hales PW, Saunders DE, Clark CA, Kirkham FJ. Vascular instability and neurological morbidity in sickle cell disease: an integrative framework. Front Neurol. 2019;10:871. doi:10.3389/fneur.2019.00871
  • Schatz J, White DA, Moinuddin A, Armstrong M, DeBaun MR. Lesion burden and cognitive morbidity in children with sickle cell disease. J Child Neurol. 2002;17(12):890–894. doi:10.1177/08830738020170122401
  • Vichinsky EP, Neumayr LD, Gold JI, et al. Neuropsychological dysfunction and neuroimaging abnormalities in neurologically intact adults with sickle cell anemia. JAMA. 2010;303(18):1823–1831. doi:10.1001/jama.2010.562
  • Prussien KV, Jordan LC, DeBaun MR, Compas BE. Cognitive function in sickle cell disease across domains, cerebral infarct status, and the lifespan: a meta-analysis. J Pediatr Psychol. 2019;44(8):948–958. doi:10.1093/jpepsy/jsz031
  • Portela GT, Butters MA, Brooks MM, Candra L, Rosano C, Novelli EM. Comprehensive assessment of cognitive function in adults with moderate and severe sickle cell disease. Am J Hematol. 2022;97(9):E344–E346. doi:10.1002/ajh.26643
  • Adams RJ, Nichols FT, Figueroa R, McKie V, Lott T. Transcranial Doppler correlation with cerebral angiography in sickle cell disease. Stroke. 1992;23(8):1073–1077. doi:10.1161/01.str.23.8.1073
  • Siegel MJ, Luker GD, Glauser TA, DeBaun MR. Cerebral infarction in sickle cell disease: transcranial Doppler US versus neurologic examination. Radiology. 1995;197(1):191–194. doi:10.1148/radiology.197.1.7568822
  • Silva GS, Vicari P, Figueiredo MS, Carrete H, Idagawa MH, Massaro AR. Brain magnetic resonance imaging abnormalities in adult patients with sickle cell disease: correlation with transcranial Doppler findings. Stroke. 2009;40(7):2408–2412. doi:10.1161/STROKEAHA.108.537415
  • Adams RJ, McKie VC, Brambilla D, et al. Stroke prevention trial in sickle cell anemia. Control Clin Trials. 1998;19(1):110–129.
  • Hankins JS, Fortner GL, McCarville MB, et al. The natural history of conditional transcranial Doppler flow velocities in children with sickle cell anaemia. Br J Haematol. 2008;142(1):94–99. doi:10.1111/j.1365-2141.2008.07167.x
  • Jones AM, Seibert JJ, Nichols FT, et al. Comparison of transcranial color Doppler imaging (TCDI) and transcranial Doppler (TCD) in children with sickle-cell anemia. Pediatr Radiol. 2001;31(7):461–469. doi:10.1007/s002470100427
  • McCarville MB, Li C, Xiong X, Wang W. Comparison of transcranial Doppler sonography with and without imaging in the evaluation of children with sickle cell anemia. Am J Roentgenol. 2004;183(4):1117–1122. doi:10.2214/ajr.183.4.1831117
  • Lee L, Smith-Whitley K, Banks S, Puckrein G. Reducing health care disparities in sickle cell disease: a review. Public Health Rep. 2019;134(6):599–607. doi:10.1177/0033354919881438
  • Wailoo K. Dying in the city of the blues: sickle cell anemia and the politics of race and health. Studies in social medicine. University of North Carolina Press; 2001. Available from: http://www.loc.gov/catdir/samples/unc041/00062865.html. Accessed April 2, 2015.
  • 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. N Engl J Med. 1998;339(1):5–11. doi:10.1056/NEJM199807023390102
  • Lee MT, Piomelli S, Granger S, et al. Stroke Prevention Trial in Sickle Cell Anemia (STOP): extended follow-up and final results. Blood. 2006;108(3):847–852. doi:10.1182/blood-2005-10-009506
  • Abboud MR, Yim E, Musallam KM, Adams RJ. Discontinuing prophylactic transfusions increases the risk of silent brain infarction in children with sickle cell disease: data from STOP II. Blood. 2011;118(4):894–898. doi:10.1182/blood-2010-12-326298
  • Wayne AS, Kevy SV, Nathan DG. Transfusion management of sickle cell disease. Blood. 1993;81(5):1109–1123.
  • Wahl S, Quirolo KC. Current issues in blood transfusion for sickle cell disease. Curr Opin Pediatr. 2009;21(1):15–21. doi:10.1097/MOP.0b013e328321882e
  • Marouf R. Blood transfusion in sickle cell disease. Hemoglobin. 2011;35(5–6):495–502. doi:10.3109/03630269.2011.596984
  • 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
  • Howard J. Sickle cell disease: when and how to transfuse. Hematology Am Soc Hematol Educ Program. 2016;2016(1):625–631.
  • Talano JAM, Hillery CA, Gottschall JL, Baylerian DM, Scott JP. Delayed hemolytic transfusion reaction/hyperhemolysis syndrome in children with sickle cell disease. Pediatrics. 2003;111(6 Pt 1):e661–665.
  • Win N. Hyperhemolysis syndrome in sickle cell disease. Expert Rev Hematol. 2009;2(2):111–115. doi:10.1586/ehm.09.2
  • Yazdanbakhsh K, Ware RE, Noizat-Pirenne F. Red blood cell alloimmunization in sickle cell disease: pathophysiology, risk factors, and transfusion management. Blood. 2012;120(3):528–537. doi:10.1182/blood-2011-11-327361
  • Linder GE, Chou ST. Red cell transfusion and alloimmunization in sickle cell disease. Haematologica. 2021;106(7):1805–1815. doi:10.3324/haematol.2020.270546
  • LaSalle-Williams M, Nuss R, Le T, et al. Extended red blood cell antigen matching for transfusions in sickle cell disease: a review of a 14-year experience from a single center (CME). Transfusion. 2011;51(8):1732–1739. doi:10.1111/j.1537-2995.2010.03045.x
  • Casas J, Friedman DF, Jackson T, Vege S, Westhoff CM, Chou ST. Changing practice: red blood cell typing by molecular methods for patients with sickle cell disease. Transfusion. 2015. doi:10.1111/trf.12987
  • Coates TD, Wood JC. How we manage iron overload in sickle cell patients. Br J Haematol. 2017;177(5):703–716. doi:10.1111/bjh.14575
  • Wilson SR, Sears M, Williams E, et al. Gaps in the diagnosis and management of iron overload in sickle cell disease: a “real-world” report from the GRNDaD registry. Br J Haematol. 2021;195(5):e157–e160. doi:10.1111/bjh.17762
  • Adamkiewicz TV, Abboud MR, Paley C, et al. Serum ferritin level changes in children with sickle cell disease on chronic blood transfusion are nonlinear and are associated with iron load and liver injury. Blood. 2009;114(21):4632–4638. doi:10.1182/blood-2009-02-203323
  • Wood JC. Estimating tissue iron burden: current status and future prospects. Br J Haematol. 2015;170(1):15–28. doi:10.1111/bjh.13374
  • Vichinsky E, Onyekwere O, Porter J, 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(3):501–508. doi:10.1111/j.1365-2141.2006.06455.x
  • Vichinsky E, Pakbaz Z, Onyekwere O, et al. Patient-reported outcomes of deferasirox (Exjade, ICL670) versus deferoxamine in sickle cell disease patients with transfusional hemosiderosis. Substudy of a randomized open-label Phase II trial. Acta Haematol. 2008;119(3):133–141. doi:10.1159/000125550
  • Treadwell MJ, Law AW, Sung J, et al. Barriers to adherence of deferoxamine usage in sickle cell disease. Pediatr Blood Cancer. 2005;44(5):500–507. doi:10.1002/pbc.20290
  • Novartis. Exjade (Deferasirox). United States Food and Drug Administration; 2013. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021882s019lbl.pdf. Accessed November 21, 2022.
  • Velasquez J, Wray AA. Deferoxamine. In: StatPearls. StatPearls Publishing; 2022. Available from: http://www.ncbi.nlm.nih.gov/books/NBK557654/. Accessed November 21, 2022.
  • Calvaruso G, Vitrano A, Di Maggio R, et al. Deferiprone versus deferoxamine in sickle cell disease: results from a 5-year long-term Italian multi-center randomized clinical trial. Blood Cells Mol Dis. 2014;53(4):265–271. doi:10.1016/j.bcmd.2014.04.004
  • Elalfy MS, Hamdy M, El Beshlawy A, et al. Deferiprone for transfusional iron overload in sickle cell disease and other anemias: open-label study of up to 3 years. Blood Adv. 2022:bloodadvances.2021006778. doi:10.1182/bloodadvances.2021006778
  • 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
  • Treadwell MJ, Du L, Bhasin N, et al. Barriers to hydroxyurea use from the perspectives of providers, individuals with sickle cell disease, and families: report from a U.S. regional collaborative. Front Genet. 2022;13:921432. doi:10.3389/fgene.2022.921432
  • Vick L, Potts M, Jaskowiak M, Gibson RW. Hydroxyurea adherence strategies for persons with sickle cell disease: a systematic review. J Health Care Poor Underserved. 2021;32(1):99–118. doi:10.1353/hpu.2021.0011
  • Hodges JR, Phillips SM, Norell S, et al. Intentional and unintentional nonadherence to hydroxyurea among people with sickle cell disease: a qualitative study. Blood Adv. 2020;4(18):4463–4473. doi:10.1182/bloodadvances.2020001701
  • Steinberg MH, McCarthy WF, Castro O, et al. The risks and benefits of long-term use of hydroxyurea in sickle cell anemia: a 17.5 year follow-up. Am J Hematol. 2010;85(6):403–408. doi:10.1002/ajh.21699
  • Rodriguez A, Duez P, Dedeken L, Cotton F, Ferster A. Hydroxyurea (hydroxycarbamide) genotoxicity in pediatric patients with sickle cell disease. Pediatr Blood Cancer. 2018;65(7):e27022. doi:10.1002/pbc.27022
  • Rankine-Mullings AE, Nevitt SJ. Hydroxyurea (hydroxycarbamide) for sickle cell disease. Cochrane Database Syst Rev. 2022;(9). doi:10.1002/14651858.CD002202.pub3
  • Wang WC, Ware RE, Miller ST, et al. Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG). Lancet. 2011;377(9778):1663–1672. doi:10.1016/S0140-6736(11)60355-3
  • Lebensburger JD, Miller ST, Howard TH, et al. Influence of severity of anemia on clinical findings in infants with sickle cell anemia: analyses from the BABY HUG study. Pediatr Blood Cancer. 2012;59(4):675–678. doi:10.1002/pbc.24037
  • Smart LR, Ambrose EE, Balyorugulu G, et al. Stroke Prevention with Hydroxyurea Enabled through Research and Education (SPHERE): a Phase 2 primary stroke prevention trial in Sub-Saharan Africa. AHA. 2022;145(6):66. doi:10.1159/000526322
  • Miller ST, Macklin EA, Pegelow CH, 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. The Journal of Pediatrics. 2001;139(3):385–390. doi:10.1067/mpd.2001.117580.
  • DeBaun MR, Armstrong FD, McKinstry RC, Ware RE, Vichinsky E, Kirkham FJ. Silent cerebral infarcts: a review on a prevalent and progressive cause of neurologic injury in sickle cell anemia. Blood. 2012;119(20):4587–4596. doi:10.1182/blood-2011-02-272682
  • DeBaun MR, Gordon M, McKinstry RC, et al. Controlled trial of transfusions for silent cerebral infarcts in sickle cell anemia. N Engl J Med. 2014;371(8):699–710. doi:10.1056/NEJMoa1401731
  • Guilliams KP, Fields ME, Hulbert ML. Higher-than-expected prevalence of silent cerebral infarcts in children with hemoglobin SC disease. Blood. 2015;125(2):416–417. doi:10.1182/blood-2014-10-605964
  • Sathi BK, Yoshida Y, Weaver MR, et al. Unusually high prevalence of stroke and cerebral vasculopathy in hemoglobin SC Disease: a Retrospective Single Institution Study. Acta Haematol. 2022;145(2):160–169. doi:10.1159/000519360
  • Hasson C, Veling L, Rico J, Mhaskar R. The role of hydroxyurea to prevent silent stroke in sickle cell disease. Medicine. 2019;98(51):e18225. doi:10.1097/MD.0000000000018225
  • Fields ME, Guilliams KP, Ragan D, et al. Hydroxyurea reduces cerebral metabolic stress in patients with sickle cell anemia. Blood. 2019;133(22):2436–2444. doi:10.1182/blood-2018-09-876318
  • Estcourt LJ, Kimber C, Hopewell S, Trivella M, Doree C, Abboud MR. Interventions for preventing silent cerebral infarcts in people with sickle cell disease. Cochrane Database Syst Rev. 2020;4:CD012389. doi:10.1002/14651858.CD012389.pub3
  • Powars D, Wilson B, Imbus C, Pegelow C, Allen J. The natural history of stroke in sickle cell disease. Am J Med. 1978;65(3):461–471.
  • Webb J, Kwiatkowski JL. Stroke in patients with sickle cell disease. Expert Rev Hematol. 2013;6(3):301–316. doi:10.1586/ehm.13.25
  • Rafay MF, Shapiro KA, Surmava AM, et al. Spectrum of cerebral arteriopathies in children with arterial ischemic stroke. Neurology. 2020;94(23):e2479–e2490. doi:10.1212/WNL.0000000000009557
  • Aa K, Na G. How I treat and manage strokes in sickle cell disease. Blood. 2015;125(22). doi:10.1182/blood-2014-09-551564
  • Hulbert ML, Scothorn DJ, Panepinto JA, et al. Exchange blood transfusion compared with simple transfusion for first overt stroke is associated with a lower risk of subsequent stroke: a retrospective cohort study of 137 children with sickle cell anemia. J Pediatr. 2006;149(5):710–712. doi:10.1016/j.jpeds.2006.06.037
  • Hurlet-Jensen AM, Prohovnik I, Pavlakis SG, Piomelli S. Effects of total hemoglobin and hemoglobin S concentration on cerebral blood flow during transfusion therapy to prevent stroke in sickle cell disease. Stroke. 1994;25(8):1688–1692. doi:10.1161/01.str.25.8.1688
  • Strouse JJ, Lanzkron S, Urrutia V. The epidemiology, evaluation and treatment of stroke in adults with sickle cell disease. Expert Rev Hematol. 2011;4(6):597–606. doi:10.1586/ehm.11.61
  • Frye RE. Reversible posterior leukoencephalopathy syndrome in sickle-cell anemia. Pediatr Neurol. 2009;40(4):298–301. doi:10.1016/j.pediatrneurol.2008.10.024
  • Hinchey J, Chaves C, Appignani B, et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med. 1996;334(8):494–500. doi:10.1056/NEJM199602223340803
  • Raj S, Killinger J, Overby P. Blood transfusion in sickle cell disease leading to posterior reversible encephalopathy syndrome (PRES). J Child Neurol. 2013;28(10):1284–1286. doi:10.1177/0883073812453497
  • Vargas A, Testai FD. Posterior reversible encephalopathy syndrome in adult sickle-cell patients: case series and literature review. J Clin Neurosci. 2019;70:249–250. doi:10.1016/j.jocn.2019.08.070
  • Sidani CA, Ballourah W, El Dassouki M, et al. Venous sinus thrombosis leading to stroke in a patient with sickle cell disease on hydroxyurea and high hemoglobin levels: treatment with thrombolysis. Am J Hematol. 2008;83(10):818–820. doi:10.1002/ajh.21261
  • Rahimi Z, Parsian A. Sickle cell disease and venous thromboembolism. Mediterr J Hematol Infect Dis. 2011;3(1):e2011024. doi:10.4084/MJHID.2011.024
  • Lusher JM, Haghighat H, Khalifa AS. A prophylactic transfusion program for children with sickle cell anemia complicated by CNS infarction. Am J Hematol. 1976;1(2):265–273. doi:10.1002/ajh.2830010210
  • Russell M, Goldberg H, Hodson A, et al. Effect of transfusion therapy on arteriographic abnormalities and on recurrence of stroke in sickle cell disease. Blood. 1984;63(1):162–169. doi:10.1182/blood.V63.1.162.162
  • Pegelow CH, Adams RJ, McKie V, et al. Risk of recurrent stroke in patients with sickle cell disease treated with erythrocyte transfusions. J Pediatr. 1995;126(6):896–899. doi:10.1016/S0022-3476(95)70204-0
  • Estcourt LJ, Kohli R, Hopewell S, Trivella M, Wang WC. Blood transfusion for preventing primary and secondary stroke in people with sickle cell disease. Cochrane Database Syst Rev. 2020;7:CD003146. doi:10.1002/14651858.CD003146.pub4
  • Ware RE, Helms RW. Stroke With Transfusions Changing to Hydroxyurea (SWiTCH). Blood. 2012;119(17):3925–3932. doi:10.1182/blood-2011-11-392340
  • Kayle M, Docherty SL, Sloane R, et al. Transition to adult care in sickle cell disease: a longitudinal study of clinical characteristics and disease severity. Pediatr Blood Cancer. 2019;66(1):e27463. doi:10.1002/pbc.27463
  • Lanzkron S, Carroll CP, Haywood C. Mortality rates and age at death from sickle cell disease: u.S., 1979–2005. Public Health Rep. 2013;128(2):110–116. doi:10.1177/003335491312800206
  • Anie KA, Telfair J; Sickle Cell Disease Transition Study Working Group. Multi-site study of transition in adolescents with sickle cell disease in the United Kingdom and the United States. Int J Adolesc Med Health. 2005;17(2):169–178. doi:10.1515/ijamh.2005.17.2.169
  • Treadwell M, Telfair J, Gibson RW, Johnson S, Osunkwo I. Transition from pediatric to adult care in sickle cell disease: establishing evidence-based practice and directions for research. Am J Hematol. 2011;86(1):116–120. doi:10.1002/ajh.21880
  • Treadwell M, Johnson S, Sisler I, et al. Development of a sickle cell disease readiness for transition assessment. Int J Adolesc Med Health. 2016;28(2):193–201. doi:10.1515/ijamh-2015-0010
  • Currie S, Raghavan A, Batty R, Connolly DJA, Griffiths PD. Childhood moyamoya disease and moyamoya syndrome: a pictorial review. Pediatr Neurol. 2011;44(6):401–413. doi:10.1016/j.pediatrneurol.2011.02.007
  • Dobson SR, Holden KR, Nietert PJ, et al. Moyamoya syndrome in childhood sickle cell disease: a predictive factor for recurrent cerebrovascular events. Blood. 2002;99(9):3144–3150.
  • Griessenauer CJ, Lebensburger JD, Chua MH, et al. Encephaloduroarteriosynangiosis and encephalomyoarteriosynangiosis for treatment of moyamoya syndrome in pediatric patients with sickle cell disease. J Neurosurg Pediatr. 2015:1–10. doi:10.3171/2014.12.PEDS14522
  • Winstead M, Sun PP, Martin K, et al. Encephaloduroarteriosynangiosis (EDAS) in young patients with cerebrovascular complications of sickle cell disease: single-institution experience. Pediatr Hematol Oncol. 2017;34(2):100–106. doi:10.1080/08880018.2017.1313917
  • Alamri A, Hever P, Cheserem J, Gradil C, Bassi S, Tolias CM. Encephaloduroateriosynangiosis (EDAS) in the management of Moyamoya syndrome in children with sickle cell disease. Br J Neurosurg. 2019;33(2):161–164. doi:10.1080/02688697.2017.1339227
  • Gluckman E, Cappelli B, Bernaudin F, et al. Sickle cell disease: an international survey of results of HLA-identical sibling hematopoietic stem cell transplantation. Blood. 2016. doi:10.1182/blood-2016-10-745711
  • Khemani K, Katoch D, Krishnamurti L. Curative therapies for sickle cell disease. Ochsner J. 2019;19(2):131–137. doi:10.31486/toj.18.0044
  • Verlhac S, Gabor F, Paillard P, et al. Improved stenosis outcome in stroke-free sickle cell anemia children after transplantation compared to chronic transfusion. Br J Haematol. 2021;193(1). doi:10.1111/bjh.17178
  • Thurn S, Kleinschmidt K, Kovacic I, et al. Transcranial Doppler sonography and the effect of haematopoietic stem cell transplantation in sickle cell disease. Neurol Res Pract. 2022;4(1):12. doi:10.1186/s42466-022-00175-y
  • Wailoo K, Pemberton S. The Troubled Dream of Genetic Medicine: Ethnicity and Innovation in Tay-Sachs, Cystic Fibrosis, and Sickle Cell Disease. Johns Hopkins University Press; 2006. Available from: http://ebookcentral.proquest.com/lib/unc/detail.action?docID=3318266. Accessed March 18, 2022.
  • DeBaun MR, Clayton EW. Primum non nocere: the case against transplant for children with sickle cell anemia without progressive end-organ disease. Blood Adv. 2017;1(26):2568–2571. doi:10.1182/bloodadvances.2017007690
  • Fitzhugh CD, Walters MC. The case for HLA-identical sibling hematopoietic stem cell transplantation in children with symptomatic sickle cell anemia. Blood Adv. 2017;1(26):2563–2567. doi:10.1182/bloodadvances.2017007708
  • Stenger E, Xiang Y, Wetzel M, et al. Long-term organ function after HCT for SCD: a report from the sickle cell transplant advocacy and research alliance. Transplant Cell Ther. 2022:S2666-6367(22)01708–0. doi:10.1016/j.jtct.2022.10.012
  • 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
  • Ngwube A, Shah N, Godder K, Jacobsohn D, Hulbert ML, Shenoy S. Abatacept is effective as GVHD prophylaxis in unrelated donor stem cell transplantation for children with severe sickle cell disease. Blood Adv. 2020;4(16):3894–3899. doi:10.1182/bloodadvances.2020002236
  • Kasow KA, Krajewski J, Haines H, et al. Curing children with sickle hemoglobinopathies of varying severity early in life with HLA-matched sibling donor (MSD) hematopoietic cell transplantation (HCT) following a reduced intensity conditioning (RIC) regimen: a Sickle Transplant, Advocacy, and Research (STAR) trial. Transplant Cell Ther. 2021;29(2S):S293.
  • Krishnamurti L, Neuberg DS, Sullivan KM, et al. Bone marrow transplantation for adolescents and young adults with sickle cell disease: results of a prospective multicenter pilot study. Am J Hematol. 2019;94(4):446–454. doi:10.1002/ajh.25401
  • Stimpson SJ, DeBaun M. Comparing outcomes for young adults with severe SCD treated with HLA-identical sibling and matched unrelated HCT versus standard supportive care. Hematologist. 2016;13:3. doi:10.1182/hem.V13.3.5469
  • 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
  • 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. 2016;22(3):441–448. doi:10.1016/j.bbmt.2015.08.036
  • Nickel RS, Chiang K, Hardy SJ, et al. Nonmyeloablative HLA-identical sibling donor transplantation for children and young adults with sickle cell disease: interim results of the SUN multicenter phase II trial. Blood. 2021;138:1799. doi:10.1182/blood-2021-144454
  • Carden MA, Little J. Emerging disease-modifying therapies for sickle cell disease. Haematologica. 2019;104(9):1710–1719. doi:10.3324/haematol.2018.207357
  • Migotsky M, Beestrum M, Badawy SM. Recent advances in sickle-cell disease therapies: a review of voxelotor, crizanlizumab, and L-glutamine. Pharmacy. 2022;10(5):123. doi:10.3390/pharmacy10050123
  • Ataga KI, Kutlar A, Kanter J, et al. SUSTAIN: a multicenter, randomized, placebo-controlled, double-blind, 12-month study to assess safety and efficacy of SelG1 with or without hydroxyurea therapy in sickle cell disease patients with sickle cell-related pain crises. Blood. 2016;128(22):1. doi:10.1182/blood.V128.22.1.1
  • Safo MK, Kato GJ. Therapeutic strategies to alter the oxygen affinity of sickle hemoglobin. Hematol Oncol Clin North Am. 2014;28(2):217–231. doi:10.1016/j.hoc.2013.11.001
  • Ki JH, Rc A. 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. doi:10.1016/S2352-3026(21)00059-4
  • Hebbel RP, Hedlund BE. Sickle hemoglobin oxygen affinity-shifting strategies have unequal cerebrovascular risks. Am J Hematol. 2018;93(3):321–325. doi:10.1002/ajh.24975
  • 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
  • Bank A, Markowitz D, Lerner N. Gene transfer. A potential approach to gene therapy for sickle cell disease. Ann N Y Acad Sci. 1989;565:37–43. doi:10.1111/j.1749-6632.1989.tb24147.x
  • Abraham AA, Tisdale JF. Gene therapy for sickle cell disease: moving from the bench to the bedside. Blood. 2021;138(11):932–941. doi:10.1182/blood.2019003776
  • Kolata G. Pioneering gene therapy freed her of sickle cell. Is a cure at hand? The New York Times; 2021. Available from: https://www.nytimes.com/2021/09/14/health/sickle-cell-cure.html. Accessed November 22, 2022.
  • Stein R. First sickle cell patient treated with CRISPR gene-editing still thriving. NPR; 2021. Available from: https://www.npr.org/sections/health-shots/2021/12/31/1067400512/first-sickle-cell-patient-treated-with-crispr-gene-editing-still-thriving. Accessed November 22, 2022.
  • 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
  • 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
  • Kohn DB, Sadelain M, Glorioso JC. Occurrence of leukaemia following gene therapy of X-linked SCID. Nat Rev Cancer. 2003;3(7):477–488. doi:10.1038/nrc1122
  • Jones RJ, DeBaun MR. Leukemia after gene therapy for sickle cell disease: insertional mutagenesis, busulfan, both, or neither. Blood. 2021;138(11):942–947. doi:10.1182/blood.2021011488