Characterization of Polycythemia Vera Patients at High Altitude: A Restrospective Study from Bogotá, Colombia
Authors: Duque Nicolas , Wills Beatriz , Agudelo Claudia , Tamayo Mateo , Velasquez Elena , Taub Dana , Uchima Maria Paula , Monsalve Maria Paula , Romero Prieto Martha , Buitrago Luis , Borda Molina Andres , Camargo Carmenza , Quintero Guillermo 
Published: December 2024

Introduction:
Treatment strategies for Polycythemia Vera (PV) vary according to risk stratification with the goal to reduce thrombotic events, disease progression and disease burden. Prior studies suggest that a hematocrit target of less than 45% is associated with improved outcomes compared to higher hematocrit thresholds (Marchioli et al., 2013). However, the impact of high-altitude settings on PV presentation and treatment outcomes is not well-documented.
Methods:
We conducted a retrospective single-center study of patients diagnosed with PV residing at a high altitude (2600 meters above sea level) in Bogotá, Colombia. Data was collected from electronic medical records including demographics, hematologic parameters, bone marrow biopsy (BMB) results, thrombotic history, and treatment responses. Responses were assessed using the ELN and IWG-MRT consensus (Barosi et al., 2013). The Kaplan-Meier method was used to estimate overall survival (OS) from the time of PV diagnosis.
Results:
Overall, 59 patients had complete follow-up data, with a median age of 60 years at diagnosis; 46 patients (78%) were men. At presentation, 13 patients (22%) had recently experienced a thrombotic event. The mean hemoglobin (Hb) and hematocrit levels at diagnosis were 19.6 g/dL (13.3-23.4) and 57.6% (41.7-69.9), respectively, with a mean Hb of 18.4 g/dL and hematocrit of 56.5% for women and a mean Hb of 20.2 g/dL and hematocrit of 58.9% for males. Our study demonstrates an increase of at least 12% in mean hematocrit and 5 g/dL in Hb compared to historical controls at sea-level settings (Grunwald et al., 2018; Vannucchi et al., 2015). The median erythropoietin (EPO) level at diagnosis was 4.46 UI/L. Baseline BMB revealed grade 1-2 myelofibrosis in 30.5% of patients, while 42.4% had hypercellular bone marrow. The most frequent treatment approach was a combination of Hydroxyurea (HU) and Aspirin (20.3%), followed by a combination of HU, Aspirin and phlebotomy (15.3%), and therapy with either HU (15.3%) or phlebotomy alone (15.3%). Antiplatelet therapy was used alone in 44% of patients, while 13.6% received only anticoagulation, and 3.4% received a combination of both. With a median follow-up of 4.25 years, the overall response rate was 59.3%, complete hematologic remission was achieved in 20.3% of cases and 12% experienced thrombosis since the start of treatment. After one year of treatment, the mean Hb was 16.9 g/dL (11.7-21.2) and the mean hematocrit level was 50.86% (34.3-64.8), with only 20.3% of patients meeting a hematocrit goal &lt; 45%. The average number of phlebotomy sessions per year needed to achieve a hematocrit &lt; 45% was 5.4. The median estimated 5-year OS for the whole cohort was 90% (95% CI: 72%, 97%), without significant differences among patients with hematocrit &lt; 45% (OS of 89%, 95% CI: 43%, 98%) versus patients with hematocrit ≥ 45% (OS of 90% (95% CI: 66%, 97%, p&gt; 0.05). Univariable Cox regression models revealed no statistically significant difference among several variables including sex, smoking status, hematocrit, and thrombotic events on OS.
Conclusion:
Our study highlights the unique clinical characteristics and treatment responses of PV patients living at a high-altitude setting. As expected, patients exhibited higher Hb and hematocrit than major reported studies at sea level. While only 20.3% of patients met a hematocrit goal of less than 45%, the estimated five-year OS is comparable to that reported in the literature (Verstovsek et al., 2022). Additionally, no differences in OS were found between the group with hematocrit &lt; 45% and those with hematocrit ≥ 45%, confirming that erythrocytosis is better tolerated in high-altitude settings. These findings encourage further prospective studies to define tailored PV diagnostic criteria and therapeutic strategies at high altitude settings.