In this episode, we discuss the diagnosis and management of Essential Thrombocythemia with Dr. Raajit Rampal. Here are the shownotes:
1.     IPSET (revised) system, risk categories are defined by the presence of a prior thrombosis, age, and JAK2 mutation status:

·        Very low risk: No prior thrombosis, age ≤60 years, JAK2-unmutated

·        Low risk: No prior thrombosis, age ≤60 years, JAK2-mutated

·        Intermediate risk: No thrombosis, age >60 years, JAK2-unmutated

·        High risk: History of thrombosis (any age/genotype), or age >60 years with JAK2 mutation

https://ashpublications.org/blood/article/120/26/5128/30914/Development-and-validation-of-an-International

2.    The MIPSS-ET provides points for:

·        Age > 60 years (3 points)

·        Adverse mutation (SF3B1/SRSF2/U2AF1/TP53) (2 points)

·        Male sex (1 point)

·        White blood cell count ≥11 × 10^9/L (1 point)

·        https://onlinelibrary.wiley.com/doi/abs/10.1111/bjh.16380?sid=nlm%3Apubmed

3.    Aspirin

o   Is there a benefit of twice-daily aspirin dosing, especially in high-risk or JAK2-mutant disease?

https://ashpublications.org/blood/article/136/2/171/454293/A-randomized-double-blind-trial-of-3-aspirin

4.     Cytoreduction in High-risk ET
 

Hydroxyurea: https://www.nejm.org/doi/full/10.1056/NEJM199504273321704

Pegylated interferon alfa

MPD-RC 112 Mascarenhas J et al. A randomized phase 3 trial of interferon- α vs hydroxyurea in polycythemia vera and essential thrombocythemia. Blood . 2022) 

https://ashpublications.org/blood/article/139/19/2931/483404/A-randomized-phase-3-trial-of-interferon-vs

Anagrelide in ET

https://ashpublications.org/blood/article/121/10/1720/31186/Anagrelide-compared-with-hydroxyurea-in-WHO

5.    Ruxolitinib  

In a randomized study phase 2 study (MAJIC-ET), ruxolitinib treatment did not deliver better rates of hematological response than best-available therapy, although symptoms did improve. 

·        MAJIC-ET study which is a randomized phase 2 trial 

·        ET patients resistant/intolerant to HU were randomized to receive RUX or standard treatment (HU 71%, anagrelide 48%, IFN 40%). The primary study outcome was CR, defined by normal platelet and white cell counts and normal spleen size.  

·        At 1 year, response was achieved in 46% of patients in the RUX group and in 44% in the standard arm, without statistically significant difference between the two groups.  

·        In addition, no difference was observed in the rates of thrombosis, hemorrhage, and disease transformation after 2 years of follow-up.  

·        MRs were also uncommon. RUX was superior, however, in symptom control. 

https://ashpublications.org/blood/article/130/17/1889/36509/Ruxolitinib-vs-best-available-therapy-for-ET