Cytoreductive Therapy, Phlebotomy Cut PV Mortality in Veterans

Cytoreductive therapy and phlebotomy significantly lowered all-cause mortality in veterans treated for polycythemia vera compared with veterans who had no documented treatment, according to a large retrospective analysis of the US Veterans Health Administration (VHA) database. However, neither approach outperformed the other or showed a significant edge in preventing thrombotic events, according to findings published in Cancer Treatment and Research Communications.¹

This new study is among the first to directly compare treatment patterns and outcomes across a contemporary, nationwide cohort of veterans with polycythemia vera, a population the authors describe as understudied despite the VHA’s size. They add that managing thrombotic event risk is difficult in patients without a prior thrombotic event, since there is no mandatory guideline to prescribe cytoreductive therapy to patients with polycythemia vera.

The researchers screened records from 11 million–plus veterans from the VHA and CMS databases using the International Classification of Diseases (ICD), 10th Edition, code D45 to identify a polycythemia vera diagnosis between October 2017 and December 2023. Among the initial study population of 11,809 veterans, 7151 (60.6%) had undergone cytoreductive therapy or phlebotomy. After excluding patients with thrombotic events and treatment before the index date, and for patients who initiated cytoreductive therapy within 90 days of their diagnosis, there were 5287 patients included in a mortality analysis and 5245 in a thrombotic event analysis; 93.6% were men, 78.5% reported White race, and the mean (SD) age was 64.4 (11.6) years.

What Did the Data Show on Mortality and Thrombosis Risk?

Overall, patients treated with cytoreductive therapy were older than patients treated with phlebotomy or no treatment at all (69.9 vs 62.9 vs 64.0 years, respectively), which the authors attribute to cytoreductive therapy being preferentially prescribed to higher-risk, older patients or patients with a history of thrombosis.

The median study follow-up was 4.4 years, and during the follow-up, 68 patients treated with cytoreductive therapy, 97 with phlebotomy, and 651 with no documented treatment died. Their respective follow-up periods were 4.53, 4.87, and 4.25 years.

After adjusting for demographics and baseline comorbidities, cytoreductive therapy was associated with a 43% lower mortality risk vs no treatment (HR, 0.57; 95% CI, 0.44-0.74; P < .01) and phlebotomy with a 20% lower mortality risk (HR, 0.80; 95% CI, 0.65-1.00; P = .05). Findings remained consistent using a propensity score–weighted model:

• Cytoreductive therapy: HR, 0.55 (95% CI, 0.40-0.77; P < .01)
• Phlebotomy: HR, 0.79 (95% CI, 0.63-0.99; P = .04)

Among the 9.38% of all patients who experienced a thrombotic event, most (n = 391) were from the group with no documented treatment, followed by 61 of those treated with phlebotomy and 44 with cytoreductive therapy. Of the 2 treatment methods, however, neither showed a statistically significant reduction of thrombotic events compared with no treatment:

• Cytoreductive therapy: HR, 0.91; 95% CI, 0.66-1.26; P = .58)
• Phlebotomy: HR, 0.83 (95% CI, 0.63-1.09; P = .19)

Similar results were seen after incorporating time-varying and Cox competing-risk models for death (HR, 0.85; 95% CI, 0.59-1.24; P = .40) and thrombotic event (HR, 1.50; 95% CI, 0.96-2.33; P = .07).

Result Placement Among Prior Research

The present findings align with recent research on 11,311 patients with polycythemia vera, which found that despite active treatment, 85.3% with available lab data had at least 1 hematocrit reading at or above the 45% guideline threshold linked to thromboembolic risk.² Moreover, research from farther back, also conducted among a veteran population, shows that elevated white blood cell counts may be linked to thrombotic event risk,³ underscoring the importance of comorbidity and lab data among this patient population.

Still, there are limitations to this research. There is potential for misdiagnosis from using ICD-based polycythemia vera diagnoses, and aspirin use may not have been reliably captured, likely inflating the no-documented-treatment group. The study population was also heavily skewed toward male patients, and data on key polycythemia vera–specific variables, including JAK2 allele burden and phlebotomy frequency, were not available. There was also a short follow-up.

Going forward, the authors call for studies to incorporate patient-reported outcomes and more granular comorbidity profiles, particularly given veterans’ distinct exposure history (eg, burn pits, herbicides) and higher burdens of cardiovascular disease, posttraumatic stress disorder, and sleep apnea, “factors that influence outcomes but are challenging to adjust, quantify, and analyze in a large retrospective database study.”

References

1. Li M, Wang Y, Tashi T, et al. Management of polycythemia vera to reduce thrombotic events and mortality with phlebotomy and cytoreductive therapy in Veterans Affairs healthcare system. Cancer Treat Res Commun. 2026:49:101397. doi:10.1016/j.ctarc.2026.101397
2. Shaw ML. Real-world polycythemia care often fails to control hematocrit. AJMC^®. August 6, 2026. Accessed September 9, 2026. https://www.ajmc.com/view/real-world-polycythemia-care-often-fails-to-control-hematocrit
3. AJMC staff. Increased WBC count linked with thrombotic events in patients with PV. AJMC. January 5, 2020. Accessed September 9, 2026. https://www.ajmc.com/view/increased-wbc-count-linked-with-thrombotic-events-in-patients-with-pv