Sickle cell anemia
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Section editor | |
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Benjamin Tillman, MD Vanderbilt University Nashville, TN, USA |
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Last updated on 2024-07-23: 7 regimens on this page
7 variants on this page
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Guidelines
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
ASH
- 2021: Kanter et al. American Society of Hematology 2021 guidelines for sickle cell disease: stem cell transplantation link to PMC article PubMed
- 2020: Chou et al. American Society of Hematology 2020 guidelines for sickle cell disease: transfusion support link to PMC article PubMed
- 2020: DeBaun et al. American Society of Hematology 2020 guidelines for sickle cell disease: prevention, diagnosis, and treatment of cerebrovascular disease in children and adults link to PMC article PubMed
- 2020: Brandow et al. American Society of Hematology 2020 guidelines for sickle cell disease: management of acute and chronic pain link to PMC article PubMed
- 2019: Liem et al. American Society of Hematology 2019 guidelines for sickle cell disease: cardiopulmonary and kidney disease link to PMC article PubMed
BSH
- 2021: Oteng-Ntim et al. Management of sickle cell disease in pregnancy. A British Society for Haematology Guideline PubMed
NHLBI
All lines of therapy
Crizanlizumab monotherapy
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ataga et al. 2016 (SUSTAIN) | 2013-2015 | Randomized Phase 2 (E-RT-esc) | 1. Placebo | Superior annual rate of crises (primary endpoint) |
2. Crizanlizumab; 2.5 mg/kg | Not reported |
Supportive therapy
- Crizanlizumab (Adakveo) 5 mg/kg IV once on day 1
14-day cycle for 26 cycles (1 year)
References
- SUSTAIN: Ataga KI, Kutlar A, Kanter J, Liles D, Cancado R, Friedrisch J, Guthrie TH, Knight-Madden J, Alvarez OA, Gordeuk VR, Gualandro S, Colella MP, Smith WR, Rollins SA, Stocker JW, Rother RP. Crizanlizumab for the prevention of pain crises in sickle cell disease. N Engl J Med. 2017 Feb 2;376(5):429-439. Epub 2016 Dec 3. link to original article link to PMC article dosing details in abstract have been reviewed by our editors PubMed NCT01895361
Exagamglogene autotemcel monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Frangoul et al. 2024 (CLIMB SCD-121) | 2018-11-27 to not reported | Non-randomized phase 3 (RT) |
References
- CLIMB SCD-121: Frangoul H, Locatelli F, Sharma A, Bhatia M, Mapara M, Molinari L, Wall D, Liem RI, Telfer P, Shah AJ, Cavazzana M, Corbacioglu S, Rondelli D, Meisel R, Dedeken L, Lobitz S, de Montalembert M, Steinberg MH, Walters MC, Eckrich MJ, Imren S, Bower L, Simard C, Zhou W, Xuan F, Morrow PK, Hobbs WE, Grupp SA; CLIMB SCD-121 Study Group. Exagamglogene Autotemcel for Severe Sickle Cell Disease. N Engl J Med. 2024 May 9;390(18):1649-1662. Epub 2024 Apr 24. link to original article PubMed NCT03745287
Hydroxyurea monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Charache et al. 1995 (MSH) | 1992-1994 | Phase 3 (E-esc) | Placebo | Superior annual rate of crises |
Wang et al. 2011 (BABY HUG) | 2003-2009 | Phase 3 (E-esc) | Placebo | Did not meet co-primary endpoints of splenic and renal function |
Dose and schedule modifications
Doses were subsequently adjusted, see articles for details.
References
- MSH: Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert SV, McMahon RP, Bonds DR; Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. N Engl J Med. 1995 May 18;332(20):1317-22. link to original article dosing details in abstract have been reviewed by our editors PubMed
- Update: Steinberg MH, Barton F, Castro O, Pegelow CH, Ballas SK, Kutlar A, Orringer E, Bellevue R, Olivieri N, Eckman J, Varma M, Ramirez G, Adler B, Smith W, Carlos T, Ataga K, DeCastro L, Bigelow C, Saunthararajah Y, Telfer M, Vichinsky E, Claster S, Shurin S, Bridges K, Waclawiw M, Bonds D, Terrin M. Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: risks and benefits up to 9 years of treatment. JAMA. 2003 Apr 2;289(13):1645-51. Erratum in: JAMA. 2003 Aug 13;290(6):756. link to original article PubMed
- HRQoL analysis: Ballas SK, Barton FB, Waclawiw MA, Swerdlow P, Eckman JR, Pegelow CH, Koshy M, Barton BA, Bonds DR. Hydroxyurea and sickle cell anemia: effect on quality of life. Health Qual Life Outcomes. 2006 Aug 31;4:59. link to original article link to PMC article PubMed
- BABY HUG: Wang WC, Ware RE, Miller ST, Iyer RV, Casella JF, Minniti CP, Rana S, Thornburg CD, Rogers ZR, Kalpatthi RV, Barredo JC, Brown RC, Sarnaik SA, Howard TH, Wynn LW, Kutlar A, Armstrong FD, Files BA, Goldsmith JC, Waclawiw MA, Huang X, Thompson BW; BABY HUG investigators. Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG). Lancet. 2011 May 14;377(9778):1663-72. link to original article link to PMC article PubMed NCT00006400
- NOHARM MTD: John CC, Opoka RO, Latham TS, Hume HA, Nabaggala C, Kasirye P, Ndugwa CM, Lane A, Ware RE. Hydroxyurea Dose Escalation for Sickle Cell Anemia in Sub-Saharan Africa. N Engl J Med. 2020 Jun 25;382(26):2524-2533. link to original article PubMed NCT03128515
Hydroxyurea & Voxelotor
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Vichinsky et al. 2019 (HOPE) | 2017-01 to 2018-05 | Phase 3 (E-esc) | 1. Placebo | Superior hemoglobin response (primary endpoint) |
2. Voxelotor; 900 mg/day | Not reported |
Note: no specific dose of hydroxyurea is specified, just that the dose had to be stable for at least 3 months prior to trial enrollment. Approximately two-thirds of the patients were noted to be on hydroxyurea at baseline.
Chemotherapy
- Hydroxyurea (Hydrea) (dose not specified)
Targeted therapy
- Voxelotor (Oxbryta) 1500 mg PO once per day
Continued indefinitely
References
- HOPE: Vichinsky E, Hoppe CC, Ataga KI, Ware RE, Nduba V, El-Beshlawy A, Hassab H, Achebe MM, Alkindi S, Brown RC, Diuguid DL, Telfer P, Tsitsikas DA, Elghandour A, Gordeuk VR, Kanter J, Abboud MR, Lehrer-Graiwer J, Tonda M, Intondi A, Tong B, Howard J; HOPE Trial Investigators. A Phase 3 Randomized Trial of Voxelotor in Sickle Cell Disease. N Engl J Med. 2019 Aug 8;381(6):509-519. Epub 2019 Jun 14. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT03036813
- Update: Howard J, Ataga KI, Brown RC, Achebe M, Nduba V, El-Beshlawy A, Hassab H, Agodoa I, Tonda M, Gray S, Lehrer-Graiwer J, Vichinsky E. 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 May;8(5):e323-e333. Epub 2021 Apr 7. link to original article PubMed
L-glutamine monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Niihara et al. 2018 (GLUSCC09-01) | 2010-2013 | Phase 3 (E-switch-ooc) | Placebo +/- Hydroxyurea | Superior reduction in the number of sickle cell crises through week 48 (primary endpoint) |
References
- GLUSCC09-01: Niihara Y, Miller ST, Kanter J, Lanzkron S, Smith WR, Hsu LL, Gordeuk VR, Viswanathan K, Sarnaik S, Osunkwo I, Guillaume E, Sadanandan S, Sieger L, Lasky JL, Panosyan EH, Blake OA, New TN, Bellevue R, Tran LT, Razon RL, Stark CW, Neumayr LD, Vichinsky EP; Investigators of the Phase 3 Trial of l-Glutamine in Sickle Cell Disease. A phase 3 trial of l-glutamine in sickle cell disease. N Engl J Med. 2018 Jul 19;379(3):226-235. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT01179217
RBC transfusions
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
DeBaun et al. 2014 (SIT) | 2004-2010 | Phase 3 (E-esc) | Observation | Seems to have fewer cerebral infarcts (primary endpoint) |
Supportive therapy
- RBC transfusions
References
- SIT: DeBaun MR, Gordon M, McKinstry RC, Noetzel MJ, White DA, Sarnaik SA, Meier ER, Howard TH, Majumdar S, Inusa BP, Telfer PT, Kirby-Allen M, McCavit TL, Kamdem A, Airewele G, Woods GM, Berman B, Panepinto JA, Fuh BR, Kwiatkowski JL, King AA, Fixler JM, Rhodes MM, Thompson AA, Heiny ME, Redding-Lallinger RC, Kirkham FJ, Dixon N, Gonzalez CE, Kalinyak KA, Quinn CT, Strouse JJ, Miller JP, Lehmann H, Kraut MA, Ball WS Jr, Hirtz D, Casella JF. Controlled trial of transfusions for silent cerebral infarcts in sickle cell anemia. N Engl J Med. 2014 Aug 21;371(8):699-710. link to original article link to PMC article PubMed NCT00072761
Voxelotor monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Vichinsky et al. 2019 (HOPE) | 2017-01 to 2018-05 | Phase 3 (E-esc) | 1. Placebo | Superior hemoglobin response (primary endpoint) |
2. Voxelotor; 900 mg/day | Not reported |
References
- HOPE: Vichinsky E, Hoppe CC, Ataga KI, Ware RE, Nduba V, El-Beshlawy A, Hassab H, Achebe MM, Alkindi S, Brown RC, Diuguid DL, Telfer P, Tsitsikas DA, Elghandour A, Gordeuk VR, Kanter J, Abboud MR, Lehrer-Graiwer J, Tonda M, Intondi A, Tong B, Howard J; HOPE Trial Investigators. A Phase 3 Randomized Trial of Voxelotor in Sickle Cell Disease. N Engl J Med. 2019 Aug 8;381(6):509-519. Epub 2019 Jun 14. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT03036813
- Update: Howard J, Ataga KI, Brown RC, Achebe M, Nduba V, El-Beshlawy A, Hassab H, Agodoa I, Tonda M, Gray S, Lehrer-Graiwer J, Vichinsky E. 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 May;8(5):e323-e333. Epub 2021 Apr 7. link to original article PubMed