For patients with polycythemia vera (PV), revised European LeukemiaNet criteria for starting cytoreductive therapy, primarily hydroxyurea, effectively identified increased thrombotic risk, regardless of patients’ conventional risk category. This is according to a study that was presented at the 66th American Society of Hematology Annual Meeting and Exposition.
“A surprising finding was the substantial role played by clinical signs and symptoms (CSSs) in identifying thrombotic risk in all PV risk categories,” presenting author Francesca Palandri, MD, PhD, of the University of Bologna in Italy, told ASH Clinical News. “This broad predictive value suggests that CSSs capture significant aspects of thrombotic potential, even in patients traditionally considered to be at low risk based on age and thrombotic history alone.
“Currently, thrombotic risk stratification in PV is based on age and thrombosis history, which guide the decision to initiate cytoreductive therapy,” Dr. Palandri said. “Our results indicate that CSSs can identify, within each conventionally defined risk category, a sub-cohort at increased thrombotic risk. For clinicians, integrating CSSs into routine assessment could help personalize care and identify patients who potentially need an earlier intervention, even if at low risk by conventional standards, or an intensification of cytoreductive/antithrombotic therapy.”
The PV-ARC multicenter retrospective study evaluated 739 patients with PV treated with hydroxyurea for criteria for therapy start (CTS). To apply to real-world practice, the researchers revised the criteria to include persistent/progressive leukocytosis, extreme persistent thrombocytosis, progressive splenomegaly, inadequate hematocrit control, more than six phlebotomies per year or hematocrit above 53% at diagnosis and hydroxyurea start or phlebotomy intolerance, uncontrolled cardiovascular risk factors, and severe itching.
The researchers assessed thrombosis-free survival (TFS) from hydroxyurea initiation and factors independently associated with thrombotic risk. Of the 739 patients treated with hydroxyurea, 137 (18.5%) presented as low risk (LR; age younger than 60 years and no previous thromboses) and 602 (81.5%) as high risk (HR). Of the HR group, 70.4% were older than 60 years of age (HR-AGE), and 29.6% had experienced prior thrombosis regardless of age (HR-THRO).
Revised CTS were recorded in 445 (60.3%) patients, including 95 (69.3%) LR, 242 (57.1%) HR-AGE, and 109 (61.2%) HR-THRO. More than one CTS presented in 152 (34.1%) patients, mostly in those considered LR (43.2% LR vs. 31.6% HR). Overall, the median hydroxyurea starting dose stood at 0.5 g/d, with the maximum dose of at least 1 g/d more frequently recorded in LR (70.3%) than HR-THRO (48.7%) and HR-AGE (41.9%). Overall, 94.5% of the patients used antiplatelet therapy, anticoagulant therapy, or both, with a comparable finding across risk categories.
Overall, the incidence rate ratios (IRR) of thrombosis during hydroxyurea treatment stood at 1.7% per year, which was similar in LR (1.1%) and HR-AGE (1.3%) but higher in HR-THRO (3%). For arterial thrombosis, a higher per-year IRR occurred in HR-THRO (1.1%) versus LR (0.4%) but was comparable to HR-AGE (0.6%). For venous thrombosis, a higher per-year IRR occurred in HR-THRO (1.3%) versus both LR (0.5%) and HR-AGE (0.6%).
CTS resulted in an increased per-year IRR of thrombosis versus no CTS (2.2% vs. 0.7%), with a similar outcome across all risk categories. During treatment, patients with CTS (88.7%) had a lower TFS at five years than those without CTS (96.1%). Across all risk categories, the best TFS at five years occurred in LR with no CTS (100%) and HR-AGE with no CTS (97.8%). HR-THRO with CTS showed the poorest TFS (79.5%). Further analysis, which also considered age greater than 60 years, confirmed CTS and previous thrombosis as independent predictors of thrombotic risk.
“The results emphasize the need for a more extensive, dynamic approach to thrombotic risk assessment in PV, which considers specific evolving clinical signs and symptoms in addition to age and thrombotic history. This may ultimately improve outcomes through individualized patient care,” Dr. Palandri said.
“In a further analysis, we identified specific CSSs as the most significant predictors of thrombosis,” Dr. Palandri concluded. “These particular signs, which include progressive splenomegaly, extreme thrombocytosis, and inadequate hematocrit control, are critical drivers of thrombotic risk and can more accurately guide clinical decisions.”
Any conflicts of interest declared by the authors can be found in the original abstract.
Reference
Palandri F, Elli EM, Benevolo G, et al. Revised ELN criteria in polycythemia vera identify an increased risk phenotype for thrombotic events beyond conventional risk stratification. a multicenter cooperative study. Abstract 242. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 7, 2024; San Diego, California.
