Difference between revisions of "Essential thrombocythemia"
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[[#top|Back to Top]] | [[#top|Back to Top]] | ||
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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> | <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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+ | ''Are you looking for a regimen, but can't find it here? For placebo or observational studies in this condition, please visit [[Essential thrombocythemia - null regimens|this page]]. If you still can't find it, please let us know so we can add it!''<br> | ||
+ | *''We have moved [[How I Treat]] articles to a dedicated page.'' | ||
{{TOC limit|limit=3}} | {{TOC limit|limit=3}} | ||
=Guidelines= | =Guidelines= | ||
− | *Tefferi A, Vannucchi AM, Barbui T. Essential thrombocythemia treatment algorithm 2018. Blood Cancer J. 2018 Jan 10;8(1):2. [https://doi.org/10.1038/s41408-017-0041-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29321520/ PubMed] | + | '''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.''' |
+ | *Tefferi A, Vannucchi AM, Barbui T. Essential thrombocythemia treatment algorithm 2018. Blood Cancer J. 2018 Jan 10;8(1):2. [https://doi.org/10.1038/s41408-017-0041-8 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802626/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29321520/ PubMed] | ||
==ELN== | ==ELN== | ||
− | *'''2011:''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979120/ Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet] | + | *'''2011:''' Barbui et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979120/ Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet] [https://pubmed.ncbi.nlm.nih.gov/21205761 PubMed] |
+ | |||
==ESMO== | ==ESMO== | ||
− | *'''2015:''' Vannucchi et al. [https://www.esmo.org/Guidelines/Haematological-Malignancies/Philadelphia-Chromosome-Negative-Chronic-Myeloproliferative-Neoplasms Philadelphia chromosome-negative chronic myeloproliferative neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] | + | *'''2015:''' Vannucchi et al. [https://www.esmo.org/Guidelines/Haematological-Malignancies/Philadelphia-Chromosome-Negative-Chronic-Myeloproliferative-Neoplasms Philadelphia chromosome-negative chronic myeloproliferative neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/26242182 PubMed] |
− | + | ||
− | *''NCCN does not have guidelines at this granular level; please | + | ==NCCN== |
+ | *''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1477 NCCN Guidelines - Myeloproliferative Neoplasms].'' | ||
=First-line therapy= | =First-line therapy= | ||
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|style="background-color:#1a9851"|Phase 3 (E-switch-ooc) | |style="background-color:#1a9851"|Phase 3 (E-switch-ooc) | ||
|[[#Aspirin_.26_Hydroxyurea|Hydroxyurea +/- Aspirin]] | |[[#Aspirin_.26_Hydroxyurea|Hydroxyurea +/- Aspirin]] | ||
− | |style="background-color:#eeee01"|Non-inferior composite endpoint | + | |style="background-color:#eeee01"|Non-inferior composite primary endpoint |
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6594023/ Gisslinger et al. 2019 (TEAM-ET 2.0)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6594023/ Gisslinger et al. 2019 (TEAM-ET 2.0)] | ||
− | | | + | |Not reported |
|style="background-color:#1a9851"|Phase 3 (C) | |style="background-color:#1a9851"|Phase 3 (C) | ||
− | |[[# | + | |[[#Anagrelide_monotherapy|Anagrelide]]; prolonged release |
|style="background-color:#eeee01"|Non-inferior mean platelet count | |style="background-color:#eeee01"|Non-inferior mean platelet count | ||
|- | |- | ||
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</div> | </div> | ||
<div class="toccolours" style="background-color:#fff2ae"> | <div class="toccolours" style="background-color:#fff2ae"> | ||
− | ====Dose modifications==== | + | ====Dose and schedule modifications==== |
*ANAHYDRET: [[Anagrelide (Agrylin)]] increased until maintenance of the platelet count at normal (less than or equal to 450 x 10<sup>9</sup>/L) or close to normal levels (450 to 600 x 10<sup>9</sup>/L) | *ANAHYDRET: [[Anagrelide (Agrylin)]] increased until maintenance of the platelet count at normal (less than or equal to 450 x 10<sup>9</sup>/L) or close to normal levels (450 to 600 x 10<sup>9</sup>/L) | ||
*TEAM-ET 2.0: [[Anagrelide (Agrylin)]] titrated to goal platelet count of 150 to 400 x 10<sup>9</sup>/L | *TEAM-ET 2.0: [[Anagrelide (Agrylin)]] titrated to goal platelet count of 150 to 400 x 10<sup>9</sup>/L | ||
</div></div> | </div></div> | ||
+ | |||
===References=== | ===References=== | ||
<!-- Presented in parts in abstract form at the 50th annual meeting of the American Society of Hematology, December 7, 2008. --> | <!-- Presented in parts in abstract form at the 50th annual meeting of the American Society of Hematology, December 7, 2008. --> | ||
− | # '''ANAHYDRET:''' Gisslinger H, Gotic M, Holowiecki J, Penka M, Thiele J, Kvasnicka HM, Kralovics R, Petrides PE; ANAHYDRET Study Group. Anagrelide compared with hydroxyurea in WHO-classified essential thrombocythemia: the ANAHYDRET Study, a randomized controlled trial. Blood. 2013 Mar 7;121(10):1720-8. Epub 2013 Jan 11. [ | + | # '''ANAHYDRET:''' Gisslinger H, Gotic M, Holowiecki J, Penka M, Thiele J, Kvasnicka HM, Kralovics R, Petrides PE; ANAHYDRET Study Group. Anagrelide compared with hydroxyurea in WHO-classified essential thrombocythemia: the ANAHYDRET Study, a randomized controlled trial. Blood. 2013 Mar 7;121(10):1720-8. Epub 2013 Jan 11. [https://doi.org/10.1182/blood-2012-07-443770 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3591796/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23315161/ PubMed] [https://clinicaltrials.gov/study/NCT01065038 NCT01065038] |
− | # '''TEAM-ET 2.0:''' Gisslinger H, Buxhofer-Ausch V, Hodisch J, Radinoff A, Karyagina E, Kyrcz-Krzemień S, Abdulkadyrov K, Gerbutavicius R, Melikyan A, Burgstaller S, Hus M, Kłoczko J, Yablokova V, Tzvetkov N, Całbecka M, Shneyder T, Warzocha K, Jurgutis M, Kaplanov K, Jilma B, Schoergenhofer C, Klade C. A phase III randomized, multicentre, double blind, active controlled trial to compare the efficacy and safety of two different anagrelide formulations in patients with essential thrombocythaemia - the TEAM-ET 2·0 trial. Br J Haematol. 2019 May;185(4):691-700. Epub 2019 Mar 28. [https://doi.org/10.1111/bjh.15824 link to original article] ''' | + | # '''TEAM-ET 2.0:''' Gisslinger H, Buxhofer-Ausch V, Hodisch J, Radinoff A, Karyagina E, Kyrcz-Krzemień S, Abdulkadyrov K, Gerbutavicius R, Melikyan A, Burgstaller S, Hus M, Kłoczko J, Yablokova V, Tzvetkov N, Całbecka M, Shneyder T, Warzocha K, Jurgutis M, Kaplanov K, Jilma B, Schoergenhofer C, Klade C. A phase III randomized, multicentre, double blind, active controlled trial to compare the efficacy and safety of two different anagrelide formulations in patients with essential thrombocythaemia - the TEAM-ET 2·0 trial. Br J Haematol. 2019 May;185(4):691-700. Epub 2019 Mar 28. [https://doi.org/10.1111/bjh.15824 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6594023/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30919941/ PubMed] EudraCT 2013‐003410‐41 |
==Aspirin & Anagrelide {{#subobject:fdd555|Regimen=1}}== | ==Aspirin & Anagrelide {{#subobject:fdd555|Regimen=1}}== | ||
<div class="toccolours" style="background-color:#eeeeee"> | <div class="toccolours" style="background-color:#eeeeee"> | ||
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</div> | </div> | ||
<div class="toccolours" style="background-color:#fff2ae"> | <div class="toccolours" style="background-color:#fff2ae"> | ||
− | ====Dose modifications==== | + | ====Dose and schedule modifications==== |
*[[Anagrelide (Agrylin)]] doses were subsequently adjusted to maintain the platelet count at less than 400 x 10<sup>9</sup>/L | *[[Anagrelide (Agrylin)]] doses were subsequently adjusted to maintain the platelet count at less than 400 x 10<sup>9</sup>/L | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
− | # '''UK MRC PT-1:''' Harrison CN, Campbell PJ, Buck G, Wheatley K, East CL, Bareford D, Wilkins BS, van der Walt JD, Reilly JT, Grigg AP, Revell P, Woodcock BE, Green AR; United Kingdom Medical Research Council Primary Thrombocythemia 1 Study. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med. 2005 Jul 7;353(1):33-45. [https://doi.org/10.1056/NEJMoa043800 link to original article] ''' | + | # '''UK MRC PT-1:''' Harrison CN, Campbell PJ, Buck G, Wheatley K, East CL, Bareford D, Wilkins BS, van der Walt JD, Reilly JT, Grigg AP, Revell P, Woodcock BE, Green AR; United Kingdom Medical Research Council Primary Thrombocythemia 1 Study. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med. 2005 Jul 7;353(1):33-45. [https://doi.org/10.1056/NEJMoa043800 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16000354/ PubMed] content property of [https://hemonc.org HemOnc.org] |
==Aspirin & Hydroxyurea {{#subobject:762af3|Regimen=1}}== | ==Aspirin & Hydroxyurea {{#subobject:762af3|Regimen=1}}== | ||
<div class="toccolours" style="background-color:#eeeeee"> | <div class="toccolours" style="background-color:#eeeeee"> | ||
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</div> | </div> | ||
<div class="toccolours" style="background-color:#fff2ae"> | <div class="toccolours" style="background-color:#fff2ae"> | ||
− | ====Dose modifications==== | + | ====Dose and schedule modifications==== |
*[[Hydroxyurea (Hydrea)]] doses were subsequently adjusted to maintain the platelet count at less than 400 x 10<sup>9</sup>/L | *[[Hydroxyurea (Hydrea)]] doses were subsequently adjusted to maintain the platelet count at less than 400 x 10<sup>9</sup>/L | ||
</div></div><br> | </div></div><br> | ||
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|style="background-color:#1a9851"|Phase 3 (E-switch-ooc) | |style="background-color:#1a9851"|Phase 3 (E-switch-ooc) | ||
|[[#Aspirin_.26_Anagrelide|Anagrelide +/- Aspirin]] | |[[#Aspirin_.26_Anagrelide|Anagrelide +/- Aspirin]] | ||
− | |style="background-color:#eeee01"|Non-inferior | + | |style="background-color:#eeee01"|Non-inferior composite primary endpoint |
|- | |- | ||
|} | |} | ||
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</div> | </div> | ||
<div class="toccolours" style="background-color:#fff2ae"> | <div class="toccolours" style="background-color:#fff2ae"> | ||
− | ====Dose modifications==== | + | ====Dose and schedule modifications==== |
*[[Hydroxyurea (Hydrea)]] increased until maintenance of the platelet count at normal (less than or equal to 450 x 10<sup>9</sup>/L) or close to normal levels (450 to 600 x 10<sup>9</sup>/L) | *[[Hydroxyurea (Hydrea)]] increased until maintenance of the platelet count at normal (less than or equal to 450 x 10<sup>9</sup>/L) or close to normal levels (450 to 600 x 10<sup>9</sup>/L) | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
− | # '''UK MRC PT-1:''' Harrison CN, Campbell PJ, Buck G, Wheatley K, East CL, Bareford D, Wilkins BS, van der Walt JD, Reilly JT, Grigg AP, Revell P, Woodcock BE, Green AR; United Kingdom Medical Research Council Primary Thrombocythemia 1 Study. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med. 2005 Jul 7;353(1):33-45. [https://doi.org/10.1056/NEJMoa043800 link to original article] ''' | + | # '''UK MRC PT-1:''' Harrison CN, Campbell PJ, Buck G, Wheatley K, East CL, Bareford D, Wilkins BS, van der Walt JD, Reilly JT, Grigg AP, Revell P, Woodcock BE, Green AR; United Kingdom Medical Research Council Primary Thrombocythemia 1 Study. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med. 2005 Jul 7;353(1):33-45. [https://doi.org/10.1056/NEJMoa043800 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16000354/ PubMed] |
<!-- Presented in parts in abstract form at the 50th annual meeting of the American Society of Hematology, December 7, 2008. --> | <!-- Presented in parts in abstract form at the 50th annual meeting of the American Society of Hematology, December 7, 2008. --> | ||
− | # '''ANAHYDRET:''' Gisslinger H, Gotic M, Holowiecki J, Penka M, Thiele J, Kvasnicka HM, Kralovics R, Petrides PE; ANAHYDRET Study Group. Anagrelide compared with hydroxyurea in WHO-classified essential thrombocythemia: the ANAHYDRET Study, a randomized controlled trial. Blood. 2013 Mar 7;121(10):1720-8. Epub 2013 Jan 11. [ | + | # '''ANAHYDRET:''' Gisslinger H, Gotic M, Holowiecki J, Penka M, Thiele J, Kvasnicka HM, Kralovics R, Petrides PE; ANAHYDRET Study Group. Anagrelide compared with hydroxyurea in WHO-classified essential thrombocythemia: the ANAHYDRET Study, a randomized controlled trial. Blood. 2013 Mar 7;121(10):1720-8. Epub 2013 Jan 11. [https://doi.org/10.1182/blood-2012-07-443770 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3591796/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23315161/ PubMed] [https://clinicaltrials.gov/study/NCT01065038 NCT01065038] |
==Hydroxyurea monotherapy {{#subobject:762af4|Regimen=1}}== | ==Hydroxyurea monotherapy {{#subobject:762af4|Regimen=1}}== | ||
<div class="toccolours" style="background-color:#eeeeee"> | <div class="toccolours" style="background-color:#eeeeee"> | ||
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|1990-1993 | |1990-1993 | ||
|style="background-color:#1a9851"|Phase 3 (E-esc) | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
− | |[[#Observation|Observation]] | + | |[[Essential_thrombocythemia_-_null_regimens#Observation|Observation]] |
|style="background-color:#1a9850"|Superior thrombotic episode rate | |style="background-color:#1a9850"|Superior thrombotic episode rate | ||
|- | |- | ||
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</div> | </div> | ||
<div class="toccolours" style="background-color:#fff2ae"> | <div class="toccolours" style="background-color:#fff2ae"> | ||
− | ====Dose modifications==== | + | ====Dose and schedule modifications==== |
*[[Hydroxyurea (Hydrea)]] doses were subsequently adjusted to maintain the platelet count at less than 600 x 10<sup>9</sup>/L without lowering the WBC count below 4 x 10<sup>9</sup>/L | *[[Hydroxyurea (Hydrea)]] doses were subsequently adjusted to maintain the platelet count at less than 600 x 10<sup>9</sup>/L without lowering the WBC count below 4 x 10<sup>9</sup>/L | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
− | # Cortelazzo S, Finazzi G, Ruggeri M, Vestri O, Galli M, Rodeghiero F, Barbui T. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med. 1995 Apr 27;332(17):1132-6. [https://doi.org/10.1056/NEJM199504273321704 link to original article] ''' | + | # Cortelazzo S, Finazzi G, Ruggeri M, Vestri O, Galli M, Rodeghiero F, Barbui T. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med. 1995 Apr 27;332(17):1132-6. [https://doi.org/10.1056/NEJM199504273321704 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/7700286/ PubMed] |
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==Peginterferon alfa-2a monotherapy {{#subobject:83c030|Regimen=1}}== | ==Peginterferon alfa-2a monotherapy {{#subobject:83c030|Regimen=1}}== | ||
<div class="toccolours" style="background-color:#eeeeee"> | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:e22ba1|Variant=1}}=== | ===Regimen {{#subobject:e22ba1|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881362/ Quintás-Cardama et al. 2009 (MDACC DM03-0109)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881362/ Quintás-Cardama et al. 2009 (MDACC DM03-0109)] | ||
+ | |Not reported | ||
|style="background-color:#91cf61"|Phase 2 | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | ''Note: This trial had several dose de-escalations due to toxicity and the dose here | + | ''Note: This trial had several dose de-escalations due to toxicity and the dose here was the reported final starting dose.'' |
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
− | *[[Peginterferon alfa-2a (Pegasys)]] 90 mcg SC once | + | *[[Peginterferon alfa-2a (Pegasys)]] 90 mcg SC once on day 1 |
− | ''' | + | '''7-day cycles''' |
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
<!-- no pre-pub disclosed --> | <!-- no pre-pub disclosed --> | ||
− | # '''MDACC DM03-0109:''' Quintás-Cardama A, Kantarjian H, Manshouri T, Luthra R, Estrov Z, Pierce S, Richie MA, Borthakur G, Konopleva M, Cortes J, Verstovsek S. Pegylated interferon alfa-2a yields high rates of hematologic and molecular response in patients with advanced essential thrombocythemia and polycythemia vera. J Clin Oncol. 2009 Nov 10;27(32):5418-24. Epub 2009 Oct 13. [https://doi.org/10.1200/jco.2009.23.6075 link to original article] ''' | + | # '''MDACC DM03-0109:''' Quintás-Cardama A, Kantarjian H, Manshouri T, Luthra R, Estrov Z, Pierce S, Richie MA, Borthakur G, Konopleva M, Cortes J, Verstovsek S. Pegylated interferon alfa-2a yields high rates of hematologic and molecular response in patients with advanced essential thrombocythemia and polycythemia vera. J Clin Oncol. 2009 Nov 10;27(32):5418-24. Epub 2009 Oct 13. [https://doi.org/10.1200/jco.2009.23.6075 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881362/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19826111/ PubMed] [https://clinicaltrials.gov/study/NCT00452023 NCT00452023] |
− | ## '''Update:''' Quintás-Cardama A, Abdel-Wahab O, Manshouri T, Kilpivaara O, Cortes J, Roupie AL, Zhang SJ, Harris D, Estrov Z, Kantarjian H, Levine RL, Verstovsek S. Molecular analysis of patients with polycythemia vera or essential thrombocythemia receiving pegylated interferon α-2a. Blood. 2013 Aug 8;122(6):893-901. Epub 2013 Jun 19. [ | + | ## '''Update:''' Quintás-Cardama A, Abdel-Wahab O, Manshouri T, Kilpivaara O, Cortes J, Roupie AL, Zhang SJ, Harris D, Estrov Z, Kantarjian H, Levine RL, Verstovsek S. Molecular analysis of patients with polycythemia vera or essential thrombocythemia receiving pegylated interferon α-2a. Blood. 2013 Aug 8;122(6):893-901. Epub 2013 Jun 19. [https://doi.org/10.1182/blood-2012-07-442012 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739035/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23782935/ PubMed] |
## '''Update:''' Masarova L, Patel KP, Newberry KJ, Cortes J, Borthakur G, Konopleva M, Estrov Z, Kantarjian H, Verstovsek S. Pegylated interferon alfa-2a in patients with essential thrombocythaemia or polycythaemia vera: a post-hoc, median 83 month follow-up of an open-label, phase 2 trial. Lancet Haematol. 2017 Apr;4(4):e165-e175. Epub 2017 Mar 10. [https://doi.org/10.1016/S2352-3026(17)30030-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421384/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28291640/ PubMed] | ## '''Update:''' Masarova L, Patel KP, Newberry KJ, Cortes J, Borthakur G, Konopleva M, Estrov Z, Kantarjian H, Verstovsek S. Pegylated interferon alfa-2a in patients with essential thrombocythaemia or polycythaemia vera: a post-hoc, median 83 month follow-up of an open-label, phase 2 trial. Lancet Haematol. 2017 Apr;4(4):e165-e175. Epub 2017 Mar 10. [https://doi.org/10.1016/S2352-3026(17)30030-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421384/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28291640/ PubMed] | ||
=Relapsed, refractory, or intolerant to initial therapy= | =Relapsed, refractory, or intolerant to initial therapy= | ||
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!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https://www.clinicaltrials.gov/ | + | |[https://www.clinicaltrials.gov/study/NCT04285086 Awaiting publication (SURPASS ET)] |
− | |2020 | + | |2020 to not reported |
|style="background-color:#1a9851"|Phase 3 (C) | |style="background-color:#1a9851"|Phase 3 (C) | ||
− | |[[#Ropeginterferon_alfa- | + | |[[#Ropeginterferon_alfa-2b_monotherapy_666|Ropeginterferon alfa-2b]] |
|style="background-color:#d3d3d3"|Not reported | |style="background-color:#d3d3d3"|Not reported | ||
|- | |- | ||
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</div></div> | </div></div> | ||
===References=== | ===References=== | ||
− | #'''SURPASS ET:''' NCT04285086 | + | #'''SURPASS ET:''' [https://clinicaltrials.gov/study/NCT04285086 NCT04285086] |
+ | |||
==Peginterferon alfa-2a monotherapy {{#subobject:9180b8|Regimen=1}}== | ==Peginterferon alfa-2a monotherapy {{#subobject:9180b8|Regimen=1}}== | ||
<div class="toccolours" style="background-color:#eeeeee"> | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:ee3318|Variant=1}}=== | ===Regimen {{#subobject:ee3318|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2015-07-659060 Verger et al. 2015] |
+ | |Not reported | ||
|style="background-color:#91cf61"|Observational | |style="background-color:#91cf61"|Observational | ||
|- | |- | ||
|} | |} | ||
− | ''Note: Verger et al. 2015 do not specify a protocol but rather point to the European LeukemiaNet guidelines from 2011 | + | ''Note: Verger et al. 2015 do not specify a protocol but rather point to the European LeukemiaNet guidelines from 2011.'' |
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Biomarker eligibility criteria==== | ||
+ | *CALR mutation | ||
+ | </div> | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
Line 265: | Line 254: | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
− | # Verger E, Cassinat B, Chauveau A, Dosquet C, Giraudier S, Schlageter MH, Ianotto JC, Yassin MA, Al-Dewik N, Carillo S, Legouffe E, Ugo V, Chomienne C, Kiladjian JJ. Clinical and molecular response to interferon-α therapy in essential thrombocythemia patients with CALR mutations. Blood. 2015 Dec 10;126(24):2585-91. Epub 2015 Oct 20. [ | + | # Verger E, Cassinat B, Chauveau A, Dosquet C, Giraudier S, Schlageter MH, Ianotto JC, Yassin MA, Al-Dewik N, Carillo S, Legouffe E, Ugo V, Chomienne C, Kiladjian JJ. Clinical and molecular response to interferon-α therapy in essential thrombocythemia patients with CALR mutations. Blood. 2015 Dec 10;126(24):2585-91. Epub 2015 Oct 20. [https://doi.org/10.1182/blood-2015-07-659060 link to original article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/26486786/ PubMed] |
==Ruxolitinib monotherapy {{#subobject:7f01ff|Regimen=1}}== | ==Ruxolitinib monotherapy {{#subobject:7f01ff|Regimen=1}}== | ||
<div class="toccolours" style="background-color:#eeeeee"> | <div class="toccolours" style="background-color:#eeeeee"> | ||
Line 276: | Line 265: | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5639482/ Verstovsek et al. 2017 (INCB 18424-256)] | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5639482/ Verstovsek et al. 2017 (INCB 18424-256<sub>ET</sub>)] |
|2008-07 to 2009-04 | |2008-07 to 2009-04 | ||
|style="background-color:#91cf61"|Phase 2 | |style="background-color:#91cf61"|Phase 2 | ||
Line 289: | Line 278: | ||
|- | |- | ||
|} | |} | ||
− | ''Note: | + | ''Note: recommended doses are starting doses.'' |
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | *[[Ruxolitinib (Jakafi)]] | + | *[[Ruxolitinib (Jakafi)]] by the following laboratory-based criteria: |
− | ** | + | **Platelets between 100 to 200 x 10<sup>9</sup>/L: 20 mg PO twice per day |
− | ** | + | **Platelets greater than 200 x 10<sup>9</sup>/L: 25 mg PO twice per day |
+ | ====Supportive therapy==== | ||
+ | *[[Aspirin]] 75 mg PO once per day was advised unless contraindicated (MAJIC-ET) | ||
'''Continued indefinitely''' | '''Continued indefinitely''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#fff2ae"> | ||
+ | ====Dose and schedule modifications==== | ||
+ | *INCB 18424-256<sub>ET</sub>: titrate to keep platelets less than 400 x 10<sup>9</sup>/L | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
− | # '''MAJIC-ET:''' Harrison CN, Mead AJ, Panchal A, Fox S, Yap C, Gbandi E, Houlton A, Alimam S, Ewing J, Wood M, Chen F, Coppell J, Panoskaltsis N, Knapper S, Ali S, Hamblin A, Scherber R, Dueck AC, Cross NCP, Mesa R, McMullin MF. Ruxolitinib vs best available therapy for ET intolerant or resistant to hydroxycarbamide. Blood. 2017 Oct 26;130(17):1889-1897. Epub 2017 Aug 9. [ | + | # '''MAJIC-ET:''' Harrison CN, Mead AJ, Panchal A, Fox S, Yap C, Gbandi E, Houlton A, Alimam S, Ewing J, Wood M, Chen F, Coppell J, Panoskaltsis N, Knapper S, Ali S, Hamblin A, Scherber R, Dueck AC, Cross NCP, Mesa R, McMullin MF. Ruxolitinib vs best available therapy for ET intolerant or resistant to hydroxycarbamide. Blood. 2017 Oct 26;130(17):1889-1897. Epub 2017 Aug 9. [https://doi.org/10.1182/blood-2017-05-785790 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6410531/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/29074595/ PubMed] ISRCTN61925716 |
− | # '''INCB 18424-256:''' Verstovsek S, Passamonti F, Rambaldi A, Barosi G, Rumi E, Gattoni E, Pieri L, Zhen H, Granier M, Assad A, Cazzola M, Kantarjian HM, Barbui T, Vannucchi AM. Ruxolitinib for essential thrombocythemia refractory to or intolerant of hydroxyurea: long-term phase 2 study results. Blood. 2017 Oct 12;130(15):1768-1771. Epub 2017 Aug 21. [ | + | # '''INCB 18424-256<sub>ET</sub>:''' Verstovsek S, Passamonti F, Rambaldi A, Barosi G, Rumi E, Gattoni E, Pieri L, Zhen H, Granier M, Assad A, Cazzola M, Kantarjian HM, Barbui T, Vannucchi AM. Ruxolitinib for essential thrombocythemia refractory to or intolerant of hydroxyurea: long-term phase 2 study results. Blood. 2017 Oct 12;130(15):1768-1771. Epub 2017 Aug 21. [https://doi.org/10.1182/blood-2017-02-765032 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5639482/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28827411/ PubMed] [https://clinicaltrials.gov/study/NCT00726232 NCT00726232] |
+ | |||
=Response criteria= | =Response criteria= | ||
==ELN== | ==ELN== | ||
− | *'''2009:''' [ | + | *'''2009:''' [https://doi.org/10.1182/blood-2008-09-176818 Response criteria for essential thrombocythemia and polycythemia vera: result of a European LeukemiaNet consensus conference] [https://pubmed.ncbi.nlm.nih.gov/19278953/ PubMed] |
[[Category:Essential thrombocythemia regimens]] | [[Category:Essential thrombocythemia regimens]] | ||
[[Category:Disease-specific pages]] | [[Category:Disease-specific pages]] | ||
[[Category:Myeloproliferative neoplasms]] | [[Category:Myeloproliferative neoplasms]] |
Latest revision as of 23:34, 15 July 2024
Section editor | |
---|---|
Sanjay R. Mohan, MD, MSCI Vanderbilt University Nashville, TN, USA |
8 regimens on this page
9 variants on this page
|
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.
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.
- Tefferi A, Vannucchi AM, Barbui T. Essential thrombocythemia treatment algorithm 2018. Blood Cancer J. 2018 Jan 10;8(1):2. link to original article link to PMC article PubMed
ELN
- 2011: Barbui et al. Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet PubMed
ESMO
- 2015: Vannucchi et al. Philadelphia chromosome-negative chronic myeloproliferative neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
NCCN
- NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Myeloproliferative Neoplasms.
First-line therapy
Anagrelide monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gisslinger et al. 2013 (ANAHYDRET) | 2002-2006 | Phase 3 (E-switch-ooc) | Hydroxyurea +/- Aspirin | Non-inferior composite primary endpoint |
Gisslinger et al. 2019 (TEAM-ET 2.0) | Not reported | Phase 3 (C) | Anagrelide; prolonged release | Non-inferior mean platelet count |
Anticoagulation
- Anagrelide (Agrylin) 0.5 mg PO twice per day
Supportive therapy
- ANAHYDRET: Neither aspirin nor Clopidogrel (Plavix) were required in the study, but patients who were already taking either drug for at least two weeks were allowed to continue taking it during the study per investigator discretion
Continued indefinitely
Dose and schedule modifications
- ANAHYDRET: Anagrelide (Agrylin) increased until maintenance of the platelet count at normal (less than or equal to 450 x 109/L) or close to normal levels (450 to 600 x 109/L)
- TEAM-ET 2.0: Anagrelide (Agrylin) titrated to goal platelet count of 150 to 400 x 109/L
References
- ANAHYDRET: Gisslinger H, Gotic M, Holowiecki J, Penka M, Thiele J, Kvasnicka HM, Kralovics R, Petrides PE; ANAHYDRET Study Group. Anagrelide compared with hydroxyurea in WHO-classified essential thrombocythemia: the ANAHYDRET Study, a randomized controlled trial. Blood. 2013 Mar 7;121(10):1720-8. Epub 2013 Jan 11. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT01065038
- TEAM-ET 2.0: Gisslinger H, Buxhofer-Ausch V, Hodisch J, Radinoff A, Karyagina E, Kyrcz-Krzemień S, Abdulkadyrov K, Gerbutavicius R, Melikyan A, Burgstaller S, Hus M, Kłoczko J, Yablokova V, Tzvetkov N, Całbecka M, Shneyder T, Warzocha K, Jurgutis M, Kaplanov K, Jilma B, Schoergenhofer C, Klade C. A phase III randomized, multicentre, double blind, active controlled trial to compare the efficacy and safety of two different anagrelide formulations in patients with essential thrombocythaemia - the TEAM-ET 2·0 trial. Br J Haematol. 2019 May;185(4):691-700. Epub 2019 Mar 28. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed EudraCT 2013‐003410‐41
Aspirin & Anagrelide
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Harrison et al. 2005 (UK MRC PT-1) | 1997-2002 | Phase 3 (E-switch-ooc) | Aspirin & Hydroxyurea | Seems to have inferior composite primary end point |
Anticoagulation
- Aspirin 75 mg (100 mg in Australia) PO once per day
- Anagrelide (Agrylin) 0.5 mg PO twice per day
Continued indefinitely
Dose and schedule modifications
- Anagrelide (Agrylin) doses were subsequently adjusted to maintain the platelet count at less than 400 x 109/L
References
- UK MRC PT-1: Harrison CN, Campbell PJ, Buck G, Wheatley K, East CL, Bareford D, Wilkins BS, van der Walt JD, Reilly JT, Grigg AP, Revell P, Woodcock BE, Green AR; United Kingdom Medical Research Council Primary Thrombocythemia 1 Study. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med. 2005 Jul 7;353(1):33-45. link to original article dosing details in manuscript have been reviewed by our editors PubMed content property of HemOnc.org
Aspirin & Hydroxyurea
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Harrison et al. 2005 (UK MRC PT-1) | 1997-2002 | Phase 3 (C) | Aspirin & Anagrelide | Seems to have superior composite primary end point |
Chemotherapy
- Hydroxyurea (Hydrea) 500 to 1000 mg PO once per day
Supportive therapy
- Aspirin 75 mg (100 mg in Australia) PO once per day
Continued indefinitely
Dose and schedule modifications
- Hydroxyurea (Hydrea) doses were subsequently adjusted to maintain the platelet count at less than 400 x 109/L
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gisslinger et al. 2013 (ANAHYDRET) | 2002-2006 | Phase 3 (E-switch-ooc) | Anagrelide +/- Aspirin | Non-inferior composite primary endpoint |
Chemotherapy
- Hydroxyurea (Hydrea) 1500 mg PO once per day
Supportive therapy
- Neither aspirin nor Clopidogrel (Plavix) were required in the study, but patients who were already taking either drug for at least two weeks were allowed to continue taking it during the study per investigator discretion
Continued indefinitely
Dose and schedule modifications
- Hydroxyurea (Hydrea) increased until maintenance of the platelet count at normal (less than or equal to 450 x 109/L) or close to normal levels (450 to 600 x 109/L)
References
- UK MRC PT-1: Harrison CN, Campbell PJ, Buck G, Wheatley K, East CL, Bareford D, Wilkins BS, van der Walt JD, Reilly JT, Grigg AP, Revell P, Woodcock BE, Green AR; United Kingdom Medical Research Council Primary Thrombocythemia 1 Study. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med. 2005 Jul 7;353(1):33-45. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- ANAHYDRET: Gisslinger H, Gotic M, Holowiecki J, Penka M, Thiele J, Kvasnicka HM, Kralovics R, Petrides PE; ANAHYDRET Study Group. Anagrelide compared with hydroxyurea in WHO-classified essential thrombocythemia: the ANAHYDRET Study, a randomized controlled trial. Blood. 2013 Mar 7;121(10):1720-8. Epub 2013 Jan 11. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT01065038
Hydroxyurea monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cortelazzo et al. 1995 | 1990-1993 | Phase 3 (E-esc) | Observation | Superior thrombotic episode rate |
Dose and schedule modifications
- Hydroxyurea (Hydrea) doses were subsequently adjusted to maintain the platelet count at less than 600 x 109/L without lowering the WBC count below 4 x 109/L
References
- Cortelazzo S, Finazzi G, Ruggeri M, Vestri O, Galli M, Rodeghiero F, Barbui T. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med. 1995 Apr 27;332(17):1132-6. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Peginterferon alfa-2a monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Quintás-Cardama et al. 2009 (MDACC DM03-0109) | Not reported | Phase 2 |
Note: This trial had several dose de-escalations due to toxicity and the dose here was the reported final starting dose.
References
- MDACC DM03-0109: Quintás-Cardama A, Kantarjian H, Manshouri T, Luthra R, Estrov Z, Pierce S, Richie MA, Borthakur G, Konopleva M, Cortes J, Verstovsek S. Pegylated interferon alfa-2a yields high rates of hematologic and molecular response in patients with advanced essential thrombocythemia and polycythemia vera. J Clin Oncol. 2009 Nov 10;27(32):5418-24. Epub 2009 Oct 13. link to original article dosing details in abstract have been reviewed by our editors link to PMC article PubMed NCT00452023
- Update: Quintás-Cardama A, Abdel-Wahab O, Manshouri T, Kilpivaara O, Cortes J, Roupie AL, Zhang SJ, Harris D, Estrov Z, Kantarjian H, Levine RL, Verstovsek S. Molecular analysis of patients with polycythemia vera or essential thrombocythemia receiving pegylated interferon α-2a. Blood. 2013 Aug 8;122(6):893-901. Epub 2013 Jun 19. link to original article link to PMC article PubMed
- Update: Masarova L, Patel KP, Newberry KJ, Cortes J, Borthakur G, Konopleva M, Estrov Z, Kantarjian H, Verstovsek S. Pegylated interferon alfa-2a in patients with essential thrombocythaemia or polycythaemia vera: a post-hoc, median 83 month follow-up of an open-label, phase 2 trial. Lancet Haematol. 2017 Apr;4(4):e165-e175. Epub 2017 Mar 10. link to original article link to PMC article PubMed
Relapsed, refractory, or intolerant to initial therapy
Anagrelide monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Awaiting publication (SURPASS ET) | 2020 to not reported | Phase 3 (C) | Ropeginterferon alfa-2b | Not reported |
Anticoagulation
References
- SURPASS ET: NCT04285086
Peginterferon alfa-2a monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Verger et al. 2015 | Not reported | Observational |
Note: Verger et al. 2015 do not specify a protocol but rather point to the European LeukemiaNet guidelines from 2011.
Biomarker eligibility criteria
- CALR mutation
Immunotherapy
References
- Verger E, Cassinat B, Chauveau A, Dosquet C, Giraudier S, Schlageter MH, Ianotto JC, Yassin MA, Al-Dewik N, Carillo S, Legouffe E, Ugo V, Chomienne C, Kiladjian JJ. Clinical and molecular response to interferon-α therapy in essential thrombocythemia patients with CALR mutations. Blood. 2015 Dec 10;126(24):2585-91. Epub 2015 Oct 20. link to original article does not contain dosing details PubMed
Ruxolitinib monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Verstovsek et al. 2017 (INCB 18424-256ET) | 2008-07 to 2009-04 | Phase 2 | ||
Harrison et al. 2017 (MAJIC-ET) | 2012-2015 | Randomized Phase 2 (E-switch-ooc) | "Best available therapy" | Did not meet primary endpoint of CR rate |
Note: recommended doses are starting doses.
Targeted therapy
- Ruxolitinib (Jakafi) by the following laboratory-based criteria:
- Platelets between 100 to 200 x 109/L: 20 mg PO twice per day
- Platelets greater than 200 x 109/L: 25 mg PO twice per day
Supportive therapy
- Aspirin 75 mg PO once per day was advised unless contraindicated (MAJIC-ET)
Continued indefinitely
Dose and schedule modifications
- INCB 18424-256ET: titrate to keep platelets less than 400 x 109/L
References
- MAJIC-ET: Harrison CN, Mead AJ, Panchal A, Fox S, Yap C, Gbandi E, Houlton A, Alimam S, Ewing J, Wood M, Chen F, Coppell J, Panoskaltsis N, Knapper S, Ali S, Hamblin A, Scherber R, Dueck AC, Cross NCP, Mesa R, McMullin MF. Ruxolitinib vs best available therapy for ET intolerant or resistant to hydroxycarbamide. Blood. 2017 Oct 26;130(17):1889-1897. Epub 2017 Aug 9. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed ISRCTN61925716
- INCB 18424-256ET: Verstovsek S, Passamonti F, Rambaldi A, Barosi G, Rumi E, Gattoni E, Pieri L, Zhen H, Granier M, Assad A, Cazzola M, Kantarjian HM, Barbui T, Vannucchi AM. Ruxolitinib for essential thrombocythemia refractory to or intolerant of hydroxyurea: long-term phase 2 study results. Blood. 2017 Oct 12;130(15):1768-1771. Epub 2017 Aug 21. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00726232