Sickle cell anemia

Section editors
	Shruti Chaturvedi, MBBS, MSCI Johns Hopkins University Baltimore, MD LinkedIn		Benjamin Tillman, MD Vanderbilt University Nashville, TN

6 regimens on this page 6 variants on this page

Guidelines

NHLBI

• 2014: Evidence-Based Management of Sickle Cell Disease: Expert Panel Report, 2014

All lines of therapy

Hydroxyurea monotherapy

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Regimen

Study	Evidence	Comparator	Efficacy
Charache et al. 1995 (MSH)	Phase III (E)	Placebo	Superior annual rate of crises

Chemotherapy

• Hydroxyurea (Hydrea) 15 mg/kg/day PO

Doses were subsequently adjusted, see article for details.

References

1. 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 contains protocol PubMed
   1. 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
2. QoL 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

L-glutamine monotherapy

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Regimen

Study	Evidence	Comparator	Efficacy
Niihara et al. 2018 (GLUSCC09-01)	Phase III (E)	Placebo +/- Hydroxyurea	Superior reduction in the number of sickle cell crises through week 48

Supportive therapy

• L-glutamine (Endari) 300 mg/kg PO twice per day

48-week course

References

1. 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 contains protocol PubMed

RBC transfusions

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Regimen

Study	Evidence	Comparator	Efficacy
DeBaun et al. 2014	Phase III (E)	Observation	Seems to have fewer cerebral infarcts

To be completed

Supportive therapy

• RBC transfusions

References

1. 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

Investigational agents

• Crizanlizumab (SEG101)