Our literature review identified three previously reported cases of HU-associated digital gangrene, though limited to the lower extremities - two in chronic myeloid leukemia (CML) and one in sickle cell disease (SCD). In each case, gangrene developed after prolonged HU exposure, alternative etiologies were not substantiated, and stabilization or clinical improvement followed HU withdrawal. The present case aligns with this pattern while extending the reported phenotype to well-controlled PV and upper-extremity digits. Given the small number of reported cases, the pathophysiology remains incompletely defined and is largely extrapolated from studies of more frequently described HU-associated ulceration, histopathologic reports of HU-related tissue injury, and in vitro studies of HU effects on endothelial and circulating cells. Plausible mechanisms include cumulative endothelial injury, localized thrombo-occlusive microvascular dysfunction, impaired vascular and cutaneous repair, and interaction with PV-related microvascular susceptibility. Clinicians should include HU-associated vasculopathy in the differential diagnosis of otherwise unexplained digital ischemia, as prompt drug cessation may limit progression and improve digit salvage.

P=N/A, N=200, Recruiting, Children's Hospital Medical Center, Cincinnati | Trial completion date: Dec 2026 --> Dec 2030 | Trial primary completion date: Dec 2025 --> Dec 2028

P4, N=90, Completed, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh | Recruiting --> Completed | Trial completion date: Dec 2024 --> Jan 2026 | Trial primary completion date: Jun 2024 --> Jan 2026

ORR was 57%, 20% and 25% in patients treated by intensive chemotherapy (IC), hypomethylating agents (HMA) and BSC (including low intensity treatments as hydroxyurea and low-dose cytarabine), respectively. We observed poor outcome using IC or HMA encouraging us to propose new clinical trials in this specific subgroup. Only ASCT was able to improve prognosis.

This study provides one of the first extensive characterizations of PV in southern Colombia, confirming internationally recognized clinical features, including advanced age at diagnosis, increased prevalence of cardiovascular comorbidities, and a predominance of high-risk classification. The low rate of finding JAK2 mutations suggests that molecular testing may not be as easy to get as it could be. Even if the treatment followed the guidelines, the risk of recurrence and thrombosis remained, showing that PV is a long-term and worsening condition. These findings highlight the urgent need to expand access to molecular diagnostics, develop tailored risk-adapted medicines, and initiate prospective multicenter studies in Latin America to optimize outcomes and quality of life in PV.

P1, N=30, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting

P1, N=12, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2026 --> Nov 2026 | Trial primary completion date: Jun 2026 --> Nov 2026

We describe a 71-year-old man with JAK2-positive polycythemia vera (PV) whose hematologic parameters remained suboptimally controlled under hydroxycarbamide treatment...This case demonstrates that additional mutated clones can significantly influence phenotype and disease evolution, highlighting the limitations of stepwise molecular testing. Comprehensive profiling of clonal architecture is essential to refine diagnosis and prognosis, in the NGS era.

P1, N=85, Terminated, Boundless Bio, Inc. | Trial completion date: Mar 2027 --> Mar 2026 | Active, not recruiting --> Terminated | Trial primary completion date: Sep 2026 --> Mar 2026; Decision was made to halt the study based on overall clinical experience and market considerations. This decision was not driven by any safety signal.

Secondary prevention included dual antiplatelet therapy, therapeutic phlebotomy, and cytoreductive therapy with hydroxyurea...Long-term outcomes depend on integration of standard acute coronary syndrome therapy with disease-specific cytoreductive strategies to reduce recurrent thrombosis. This case reinforces that acute coronary syndromes should not be routinely attributed to atherosclerotic disease when clinical and angiographic features are disproportionate to traditional risk profiles.

P1, N=21, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Apr 2026 --> Apr 2027

Prior Hydroxyurea (HU) use was independently associated with secondary malignancy (OR = 2.73; 95% CI 1.33-5.61; p = 0.006), alongside age and leukocytosis...Cytoreductive therapy was associated with reduced thrombotic risk, while HU exposure was linked to secondary malignancies and disease progression, probably reflecting a high disease burden in the latter. This underscores the need for refined risk stratification and long-term surveillance in LR-PV.