Are thrombosis, progression, and survival in ET predictable?
Authors: Ghaith Abu-Zeinah, Katie Erdos, Neville Lee, Ahamed Lebbe, Imane Bouhali, Mohammed Khalid, Richard T. Silver, Joseph M. Scandura
Journal: Blood Cancer Journal (2024)

To the Editor, Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm (MPN) that originates from a hematopoietic stem cell harboring a mutated JAK2, CALR, or MPL gene, or none of these three mutations (10-15% are "triple negative").Although considered the most indolent MPN, ET is linked to burdensome vasomotor symptoms, and potentially fatal complications that include thrombosis, hemorrhage, and disease progression to myelofibrosis and aggressive myeloid neoplasms.Prognostic measures to identify those at greatest risk for thrombosis, progression, and death in ET (events) are important for timely risk-adapted intervention with available treatments, and for development of interventional trials to improve event-free survival (EFS).But predicting risks of events in ET has been difficult because ET is an uncommon and clinically heterogenous chronic disease.Predicting progression and excess mortality is even more challenging because these events typically occur decades after ET diagnosis [1].Thus, retrospective analysis of large cohorts with sufficiently long follow-up is required to identify prognostic measures to stratify risk in patients with ET.Prognostic models have been developed to assess the risk of thrombosis (IPSET-thrombosis [2]) or overall survival (OS) in ET (IPSET-survival [3], MIPSS-ET [4], and triple A [AAA] [5]).This journal recently published two large retrospective ET cohorts: Gangat et al. at the Mayo Clinic (Mayo) [6] and Loscocco et al. at the Florence Center Research and Innovation of Myeloproliferative Neoplasms (CRIMM) [7]. Both studies confirmed previously identified risk factors for thrombosis, progression and/or death in ET that include older age (Age ≥ 60), male sex, elevated white blood cell count (WBC > 11 × 10 9 /L), elevated absolute neutrophil count (ANC ≥ 8 × 10 9 /L), and low absolute lymphocyte count (ALC < 1.7 × 10 9 /L) at the time of presentation.We evaluated these parameters and current risk models in our cohort of 328 adult patients with ET treated at the Weill Cornell Medicine (WCM) Silver MPN Center over a median follow-up of 6 years [8].This cohort was rigorously defined according to the 2022 World Health Organization diagnostic criteria and therefore all patients had a diagnostic bone marrow biopsy and had alternative diagnoses scrupulously ruled out.The methods of data collection, retrieval, and analysis used were previously described [9], and cohort characteristics are included in Supplementary Table 1.Thrombosis risk in both Mayo and CRIMM was related to age, mutated JAK2, and prior thrombosis, thereby affirming risk factors in the revised IPSET-thrombosis used to stratify patients into four tiers ranging from very low to high risk.Like Mayo and CRIMM, we found that patients with JAK2-mutated ET had significantly shortened thrombosis-free survival (TFS) compared to those with CALR-mutated ET (Fig. 1A).A total of 33 thromboses occurred (15 venous, 18 arterial) of which 27 (12 venous, 15 arterial) were experienced by JAK2-mutated patients.In multivariable models,