Preserving thrombosis and life years in polycythemia vera: start by reading the biology of the disease

The Swedish nationwide study by Leontyeva et al. (Haematologica, sept, 2025) revealed that patients with myeloproliferative neoplasms (MPN) continue to lose life years compared with the general population, with polycythemia vera (PV) showing a 1.8-year loss in restricted mean survival at 15 years. Despite being classified as "low risk," these younger patients lose more life years relative to agematched peers. They face decades of exposure to clonal proliferation, inflammation, and thromboinflammation, which contribute to vascular injury, myelofibrosis, and secondary cancers. Evidence suggests that early, biology-guided therapy may modify this trajectory. Interferon, particularly ropeginterferon alfa-2b, and ruxolitinib reduces JAK2V617F allele burden, systemic inflammation, as reflected by the neutrophil-to-lymphocyte ratio (NLR), and thrombosis rates, demonstrating long-term disease-modifying potential. The challenge lies in identifying which younger patients should receive cytoreductive therapy, as these treatments, while effective, may be poorly tolerated or burdensome over decades. Biological markers such as persistent leukocytosis, elevated NLR, rising JAK2V617F variant allele frequency, or high phlebotomy burden can guide treatment decisions more precisely than age alone. Tailoring therapy in younger PV patients according to disease biology and individual tolerance may prevent irreversible complications, improve quality of life, and ultimately reduce the years of life lost.