Difference between revisions of "Sickle cell anemia"

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'''Use of this site is subject to you reading and agreeing with the terms set forth in the [[HemOnc.org_-_A_Hematology_Oncology_Wiki:General_disclaimer|disclaimer]].'''
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<span id="BackToTop"></span>
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Is there a regimen missing from this list?  Would you like to share a different dosage/schedule or an additional reference for a regimen?  Have you noticed an error?  Do you have an idea that will help the site grow to better meet your needs and the needs of many others?  You are [[How_to_contribute|invited to contribute to the site]].
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[[#top|Back to Top]]
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</div>
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{{#lst:Editorial board transclusions|heme}}
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''Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit [[Sickle cell anemia - null regimens|this page]]. If you still can't find it, please let us know so we can add it!''<br>
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*''We have moved [[How I Treat]] articles to a dedicated page.''
 
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|<div style="background-color: #66FF66; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]]  |?Regimen |limit=10000|format=sum}} regimens on this page</b></font></div>
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|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]]  |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
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<div style="background-color: #66CCFF; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]]  |?Variant |limit=10000|format=sum}} variants on this page</b></font></div>
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]]  |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 
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{{TOC limit|limit=3}}
 +
=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. [https://doi.org/10.1182/bloodadvances.2021004394 American Society of Hematology 2021 guidelines for sickle cell disease: stem cell transplantation] [https://www.ncbi.nlm.nih.gov/pubmed/34581773 PubMed]
 +
*'''2020:''' Chou et al. [https://doi.org/10.1182/bloodadvances.2019001143 American Society of Hematology 2020 guidelines for sickle cell disease: transfusion support] [https://www.ncbi.nlm.nih.gov/pubmed/31985807 PubMed]
 +
*'''2020:''' DeBaun et al. [https://doi.org/10.1182/bloodadvances.2019001142 American Society of Hematology 2020 guidelines for sickle cell disease: prevention, diagnosis, and treatment of cerebrovascular disease in children and adults] [https://pubmed.ncbi.nlm.nih.gov/32298430/ PubMed]
 +
*'''2020:''' Brandow et al. [https://doi.org/10.1182/bloodadvances.2020001851 American Society of Hematology 2020 guidelines for sickle cell disease: management of acute and chronic pain] [https://www.ncbi.nlm.nih.gov/pubmed/32559294 PubMed]
 +
*'''2019:''' Liem et al. [https://ashpublications.org/bloodadvances/article/3/23/3867/429210/American-Society-of-Hematology-2019-guidelines-for American Society of Hematology 2019 guidelines for sickle cell disease: cardiopulmonary and kidney disease] [https://www.ncbi.nlm.nih.gov/pubmed/31794601 PubMed]
  
−
==Hydroxyurea (Hydrea) {{#subobject:762af4|Regimen=1}}==
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==BSH==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
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*'''2021:''' Oteng-Ntim et al. [https://doi.org/10.1111/bjh.17671 Management of sickle cell disease in pregnancy. A British Society for Haematology Guideline] [https://www.ncbi.nlm.nih.gov/pubmed/34409598 PubMed]
 +
==NHLBI==
 +
*'''2014:''' [https://www.nhlbi.nih.gov/health-pro/guidelines/sickle-cell-disease-guidelines/ Evidence-Based Management of Sickle Cell Disease: Expert Panel Report, 2014] [https://pubmed.ncbi.nlm.nih.gov/25203083/ PubMed]
 +
 
 +
=All lines of therapy=
 +
==Crizanlizumab monotherapy {{#subobject:76agc4|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:cbzecd|Variant=1}}===
 +
{| class="wikitable" style="color:white; background-color:#404040"
 +
|<small>'''FDA-recommended dose'''</small>
 +
|-
 +
|}
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Dates of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5481200/ Ataga et al. 2016 (SUSTAIN)]
 +
|rowspan=2|2013-2015
 +
|rowspan=2 style="background-color:#1a9851"|Randomized Phase 2 (E-RT-esc)
 +
|1. [[Sickle_cell_anemia_-_null_regimens#Placebo|Placebo]]
 +
|style="background-color:#1a9850"|Superior annual rate of crises (primary endpoint)
 +
|-
 +
|2. [[#Crizanlizumab_monotherapy|Crizanlizumab]]; 2.5 mg/kg
 +
|style="background-color:#d3d3d3"|Not reported
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Supportive therapy====
 +
*[[Crizanlizumab (Adakveo)]] 5 mg/kg IV once on day 1
 +
'''14-day cycle for 26 cycles (1 year)'''
 +
</div></div>
 +
===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. [https://doi.org/10.1056/NEJMoa1611770 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5481200/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27959701/ PubMed] [https://clinicaltrials.gov/study/NCT01895361 NCT01895361]
 +
==Exagamglogene autotemcel monotherapy {{#subobject:8dgex1|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:excbt2|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://doi.org/10.1056/nejmoa2309676 Frangoul et al. 2024 (CLIMB SCD-121)]
 +
|2018-11-27 to NR
 +
| style="background-color:#91cf61" |Non-randomized phase 3 (RT)
 
|-
 
|-
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|[[#toc|back to top]]
 
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Exagamglogene autotemcel (Casgevy)]]
 +
'''One course'''
 +
</div></div>
 +
===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. [https://doi.org/10.1056/nejmoa2309676 link to original article] [https://pubmed.ncbi.nlm.nih.gov/38661449/ PubMed] [https://clinicaltrials.gov/study/NCT03745287 NCT03745287]
  
 +
==Hydroxyurea monotherapy {{#subobject:762af4|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:d87ecd|Variant=1}}===
 
===Regimen {{#subobject:d87ecd|Variant=1}}===
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{| border="1" style="text-align:center;" !align="left"  
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{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
|'''Study'''
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!style="width: 20%"|Study
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|[[Levels_of_Evidence#Evidence|'''Evidence''']]
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!style="width: 20%"|Dates of enrollment
−
|'''Comparator'''
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!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[http://www.nejm.org/doi/full/10.1056/NEJM199505183322001 Charache et al. 1995 (MSH)]
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|[https://doi.org/10.1056/NEJM199505183322001 Charache et al. 1995 (MSH)]
−
|<span
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|1992-1994
−
style="background:#00CD00;
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|style="background-color:#1a9851"|Phase 3 (E-esc)
−
padding:3px 6px 3px 6px;
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|[[Sickle_cell_anemia_-_null_regimens#Placebo|Placebo]]
−
border-color:black;
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|style="background-color:#1a9850"|Superior annual rate of crises
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border-width:2px;
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|-
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border-style:solid;">Phase III</span>
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|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3133619/ Wang et al. 2011 (BABY HUG)]
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|Placebo
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|2003-2009
 +
|style="background-color:#1a9851"|Phase 3 (E-esc)
 +
|[[Sickle_cell_anemia_-_null_regimens#Placebo|Placebo]]
 +
| style="background-color:#ffffbf" |Did not meet co-primary endpoints of splenic and renal function
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Hydroxyurea (Hydrea)]] 15 mg/kg/day PO
 +
'''Continued indefinitely'''
 +
</div>
 +
<div class="toccolours" style="background-color:#fff2ae">
 +
====Dose and schedule modifications====
 +
''Doses were subsequently adjusted, see articles for details.''
 +
</div></div>
 +
===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. [https://doi.org/10.1056/NEJM199505183322001 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/7715639/ 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. [https://doi.org/10.1001/jama.289.13.1645 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12672732/ 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. [https://doi.org/10.1186/1477-7525-4-59 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1569824/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/16942629/ 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. [https://doi.org/10.1016/s0140-6736(11)60355-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3133619/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21571150/ PubMed] [https://clinicaltrials.gov/study/NCT00006400 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. [https://doi.org/10.1056/nejmoa2000146 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32579813/ PubMed] [https://clinicaltrials.gov/study/NCT03128515 NCT03128515]
  
−
*[[Hydroxyurea (Hydrea)]] 15 mg/kg/day PO
+
==Hydroxyurea & Voxelotor {{#subobject:4eugac|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:f1g718|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Dates of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|rowspan=2|[https://doi.org/10.1056/nejmoa1903212 Vichinsky et al. 2019 (HOPE)]
 +
|rowspan=2|2017-01 to 2018-05
 +
|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc)
 +
|1. [[Sickle_cell_anemia_-_null_regimens#Placebo|Placebo]]
 +
| style="background-color:#1a9850" |Superior hemoglobin response (primary endpoint)
 +
|-
 +
|2. [[#Voxelotor_monotherapy|Voxelotor]]; 900 mg/day
 +
| style="background-color:#d3d3d3" |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.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Hydroxyurea (Hydrea)]]
 +
====Targeted therapy====
 +
*[[Voxelotor (Oxbryta)]] 1500 mg PO once per day
 +
'''Continued indefinitely'''
 +
</div></div>
 +
 
 +
===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. [https://doi.org/10.1056/nejmoa1903212 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/31199090/ PubMed] [https://clinicaltrials.gov/study/NCT03036813 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. [https://doi.org/10.1016/s2352-3026(21)00059-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33838113/ PubMed]
 +
==L-glutamine monotherapy {{#subobject:4eb49b|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:feca18|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Dates of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1056/NEJMoa1715971 Niihara et al. 2018 (GLUSCC09-01)]
 +
|2010-2013
 +
|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
 +
|[[Sickle_cell_anemia_-_null_regimens#Placebo|Placebo]] +/- Hydroxyurea
 +
|style="background-color:#1a9850"|Superior reduction in the number of sickle cell crises through week 48 (primary endpoint)
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Supportive therapy====
 +
*[[L-glutamine (Endari)]] 300 mg/kg PO twice per day
 +
'''48-week course'''
 +
</div></div>
 +
===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. [https://doi.org/10.1056/NEJMoa1715971 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30021096/ PubMed] [https://clinicaltrials.gov/study/NCT01179217 NCT01179217]
 +
 
 +
==RBC transfusions==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Dates of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4195437/ DeBaun et al. 2014 (SIT)]
 +
|2004-2010
 +
|style="background-color:#1a9851"|Phase 3 (E-esc)
 +
|[[Sickle_cell_anemia_-_null_regimens#Observation|Observation]]
 +
|style="background-color:#91cf60"|Seems to have fewer cerebral infarcts (primary endpoint)
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Supportive therapy====
 +
*[[Red blood cells|RBC]] transfusions
 +
</div></div>
  
−
''Doses were subsequently adjusted, see article for details.''
+
===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. [https://doi.org/10.1056/NEJMoa1401731 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4195437/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25140956/ PubMed] [https://clinicaltrials.gov/study/NCT00072761 NCT00072761]
  
 +
==Voxelotor monotherapy {{#subobject:4eb50c|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:fug718|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Dates of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|rowspan=2|[https://doi.org/10.1056/nejmoa1903212 Vichinsky et al. 2019 (HOPE)]
 +
|rowspan=2|2017-01 to 2018-05
 +
|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc)
 +
|1. [[Sickle_cell_anemia_-_null_regimens#Placebo|Placebo]]
 +
| style="background-color:#1a9850" |Superior hemoglobin response (primary endpoint)
 +
|-
 +
|2. [[#Voxelotor_monotherapy|Voxelotor]]; 900 mg/day
 +
| style="background-color:#d3d3d3" |Not reported
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Supportive therapy====
 +
*[[Voxelotor (Oxbryta)]] 1500 mg PO once per day
 +
'''Continued indefinitely'''
 +
</div></div>
 
===References===
 
===References===
−
# Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert SV, McMahon RP, Bonds DR. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the multicenter Study of Hydroxyurea in Sickle Cell Anemia. N Engl J Med. 1995 May 18;332(20):1317-22. [http://www.nejm.org/doi/full/10.1056/NEJM199505183322001 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/7715639 PubMed]
+
# '''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. [https://doi.org/10.1056/nejmoa1903212 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/31199090/ PubMed] [https://clinicaltrials.gov/study/NCT03036813 NCT03036813]
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## '''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. [http://jama.jamanetwork.com/article.aspx?articleid=196300 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12672732 PubMed]
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## '''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. [https://doi.org/10.1016/s2352-3026(21)00059-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33838113/ PubMed]
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# '''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. [http://hqlo.biomedcentral.com/articles/10.1186/1477-7525-4-59 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16942629 PubMed]
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[[Category:Sickle cell anemia regimens]]
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[[Category:Disease-specific pages]]
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[[Category:Hemolytic process]]
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[[Category:Inherited hemoglobinopathies]]

Latest revision as of 12:30, 29 June 2024

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Section editor
Tillman Benjamin-2.jpg
 Benjamin Tillman, MD
Vanderbilt University
Nashville, TN, USA
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Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!

  • We have moved How I Treat articles to a dedicated page.
6 regimens on this page
6 variants on this page


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

BSH

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

14-day cycle for 26 cycles (1 year)

References

  1. 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 contains dosing details in abstract PubMed NCT01895361

Exagamglogene autotemcel monotherapy

Regimen

Study Dates of enrollment Evidence
Frangoul et al. 2024 (CLIMB SCD-121) 2018-11-27 to NR Non-randomized phase 3 (RT)

Targeted therapy

One course

References

  1. 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

Chemotherapy

Continued indefinitely

Dose and schedule modifications

Doses were subsequently adjusted, see articles for details.

References

  1. 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 contains dosing details in abstract 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. 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
  2. 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
  3. 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

Targeted therapy

Continued indefinitely

References

  1. 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 contains dosing details in abstract PubMed NCT03036813
    1. 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)

Supportive therapy

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 dosing details in abstract 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

  1. 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

Supportive therapy

Continued indefinitely

References

  1. 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 contains dosing details in abstract PubMed NCT03036813
    1. 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
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