Association between elevated white blood cell counts and thrombotic events in polycythemia vera: analysis from REVEAL

Aaron T. Gerds; Ruben Mesa; John M. Burke; Michael R. Grunwald; Brady L. Stein; Peg Squier; Jingbo Yu; J. E. Hamer-Maansson; Stephen T. Oh

doi:10.1182/blood.2023020232

Association between elevated white blood cell counts and thrombotic events in polycythemia vera: analysis from REVEAL

Aaron T. Gerds^*, Ruben Mesa, John M. Burke, Michael R. Grunwald, Brady L. Stein, Peg Squier, Jingbo Yu, J. E. Hamer-Maansson, Stephen T. Oh

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by clonal proliferation of hematopoietic progenitor cells and is associated with an increased risk of thrombotic events (TEs). Established risk factors for TEs in patients with PV include advanced age, TE history, and elevated hematocrit. Although an association of TE with elevated white blood cell (WBC) counts has been suggested by retrospective studies, this relationship needs further validation. The prospective observational study of patients with polycythemia vera in US clinical practices (REVEAL) study collected prospective clinical data from 2510 patients with PV with a median follow-up of 44.7 months (range, 2-59 months) from enrollment. Using time-dependent covariate Cox proportional hazards models, blood counts were individually modeled with sex, age, disease duration, TE history at enrollment (baseline covariates), and treatment (time-dependent covariate). Analysis of 2271 participants identified 142 TEs in 106 patients. Significant associations with initial TE occurrence during the study period were observed for hematocrit level >45% (hazard ratio [HR], 1.84; 95% confidence interval [95% CI], 1.234-2.749; P = .0028) and WBCs >11 × 10⁹/L (HR, 2.35; 95% CI, 1.598-3.465; P < .0001). Elevated WBC count was significantly associated with initial TE occurrence in both low-risk and high-risk PV. When hematocrit was controlled at ≤45%, WBC count >12 × 10⁹/L was significantly associated with TE occurrence (HR, 1.95; 95% CI, 1.066-3.554; P = .0300). The results support incorporation of WBC count into PV risk stratification and studies of treatment strategies, and indicate the importance of controlling both hematocrit and WBC count in disease management. This trial was registered at www.clinicaltrials.gov as #NCT02252159.

Original language	English (US)
Pages (from-to)	1646-1655
Number of pages	10
Journal	Blood
Volume	143
Issue number	16
DOIs	https://doi.org/10.1182/blood.2023020232
State	Published - Apr 18 2024

Funding

The authors thank the patients and their families, the investigators, and the site personnel who participated in this study. The authors also thank Evan M. Braunstein for his insights and guidance in the preparation of this manuscript. Medical writing and editorial assistance were provided by Rachel Shparberg and Sophie Pickles of Envision Pharma Group (Fairfield, CT) and were funded by Incyte Corporation. This study was supported by Incyte Corporation (Wilmington, DE). Contribution: J.E.H.-M. validated the results/experiments; J.E.H.-M. J.Y. and P.S. analyzed and curated the data and wrote the initial draft of the manuscript; all authors conceptualized and designed the trial, conducted the trial, provided critical review of the manuscript, and created the visualization of data for the manuscript; and P.S. provided supervision.

ASJC Scopus subject areas

Biochemistry
Immunology
Hematology
Cell Biology

Access to Document

10.1182/blood.2023020232

Cite this

@article{a5bbdd40f7ae463c81196c5f0373b8ae,

title = "Association between elevated white blood cell counts and thrombotic events in polycythemia vera: analysis from REVEAL",

abstract = "Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by clonal proliferation of hematopoietic progenitor cells and is associated with an increased risk of thrombotic events (TEs). Established risk factors for TEs in patients with PV include advanced age, TE history, and elevated hematocrit. Although an association of TE with elevated white blood cell (WBC) counts has been suggested by retrospective studies, this relationship needs further validation. The prospective observational study of patients with polycythemia vera in US clinical practices (REVEAL) study collected prospective clinical data from 2510 patients with PV with a median follow-up of 44.7 months (range, 2-59 months) from enrollment. Using time-dependent covariate Cox proportional hazards models, blood counts were individually modeled with sex, age, disease duration, TE history at enrollment (baseline covariates), and treatment (time-dependent covariate). Analysis of 2271 participants identified 142 TEs in 106 patients. Significant associations with initial TE occurrence during the study period were observed for hematocrit level >45% (hazard ratio [HR], 1.84; 95% confidence interval [95% CI], 1.234-2.749; P = .0028) and WBCs >11 × 109/L (HR, 2.35; 95% CI, 1.598-3.465; P < .0001). Elevated WBC count was significantly associated with initial TE occurrence in both low-risk and high-risk PV. When hematocrit was controlled at ≤45%, WBC count >12 × 109/L was significantly associated with TE occurrence (HR, 1.95; 95% CI, 1.066-3.554; P = .0300). The results support incorporation of WBC count into PV risk stratification and studies of treatment strategies, and indicate the importance of controlling both hematocrit and WBC count in disease management. This trial was registered at www.clinicaltrials.gov as #NCT02252159.",

author = "Gerds, {Aaron T.} and Ruben Mesa and Burke, {John M.} and Grunwald, {Michael R.} and Stein, {Brady L.} and Peg Squier and Jingbo Yu and Hamer-Maansson, {J. E.} and Oh, {Stephen T.}",

note = "Publisher Copyright: {\textcopyright} 2024 American Society of Hematology",

year = "2024",

month = apr,

day = "18",

doi = "10.1182/blood.2023020232",

language = "English (US)",

volume = "143",

pages = "1646--1655",

journal = "Blood",

issn = "0006-4971",

publisher = "Elsevier B.V.",

number = "16",

}

TY - JOUR

T1 - Association between elevated white blood cell counts and thrombotic events in polycythemia vera

T2 - analysis from REVEAL

AU - Gerds, Aaron T.

AU - Mesa, Ruben

AU - Burke, John M.

AU - Grunwald, Michael R.

AU - Stein, Brady L.

AU - Squier, Peg

AU - Yu, Jingbo

AU - Hamer-Maansson, J. E.

AU - Oh, Stephen T.

PY - 2024/4/18

Y1 - 2024/4/18

N2 - Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by clonal proliferation of hematopoietic progenitor cells and is associated with an increased risk of thrombotic events (TEs). Established risk factors for TEs in patients with PV include advanced age, TE history, and elevated hematocrit. Although an association of TE with elevated white blood cell (WBC) counts has been suggested by retrospective studies, this relationship needs further validation. The prospective observational study of patients with polycythemia vera in US clinical practices (REVEAL) study collected prospective clinical data from 2510 patients with PV with a median follow-up of 44.7 months (range, 2-59 months) from enrollment. Using time-dependent covariate Cox proportional hazards models, blood counts were individually modeled with sex, age, disease duration, TE history at enrollment (baseline covariates), and treatment (time-dependent covariate). Analysis of 2271 participants identified 142 TEs in 106 patients. Significant associations with initial TE occurrence during the study period were observed for hematocrit level >45% (hazard ratio [HR], 1.84; 95% confidence interval [95% CI], 1.234-2.749; P = .0028) and WBCs >11 × 109/L (HR, 2.35; 95% CI, 1.598-3.465; P < .0001). Elevated WBC count was significantly associated with initial TE occurrence in both low-risk and high-risk PV. When hematocrit was controlled at ≤45%, WBC count >12 × 109/L was significantly associated with TE occurrence (HR, 1.95; 95% CI, 1.066-3.554; P = .0300). The results support incorporation of WBC count into PV risk stratification and studies of treatment strategies, and indicate the importance of controlling both hematocrit and WBC count in disease management. This trial was registered at www.clinicaltrials.gov as #NCT02252159.

AB - Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by clonal proliferation of hematopoietic progenitor cells and is associated with an increased risk of thrombotic events (TEs). Established risk factors for TEs in patients with PV include advanced age, TE history, and elevated hematocrit. Although an association of TE with elevated white blood cell (WBC) counts has been suggested by retrospective studies, this relationship needs further validation. The prospective observational study of patients with polycythemia vera in US clinical practices (REVEAL) study collected prospective clinical data from 2510 patients with PV with a median follow-up of 44.7 months (range, 2-59 months) from enrollment. Using time-dependent covariate Cox proportional hazards models, blood counts were individually modeled with sex, age, disease duration, TE history at enrollment (baseline covariates), and treatment (time-dependent covariate). Analysis of 2271 participants identified 142 TEs in 106 patients. Significant associations with initial TE occurrence during the study period were observed for hematocrit level >45% (hazard ratio [HR], 1.84; 95% confidence interval [95% CI], 1.234-2.749; P = .0028) and WBCs >11 × 109/L (HR, 2.35; 95% CI, 1.598-3.465; P < .0001). Elevated WBC count was significantly associated with initial TE occurrence in both low-risk and high-risk PV. When hematocrit was controlled at ≤45%, WBC count >12 × 109/L was significantly associated with TE occurrence (HR, 1.95; 95% CI, 1.066-3.554; P = .0300). The results support incorporation of WBC count into PV risk stratification and studies of treatment strategies, and indicate the importance of controlling both hematocrit and WBC count in disease management. This trial was registered at www.clinicaltrials.gov as #NCT02252159.

UR - http://www.scopus.com/inward/record.url?scp=85184073821&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85184073821&partnerID=8YFLogxK

U2 - 10.1182/blood.2023020232

DO - 10.1182/blood.2023020232

M3 - Article

C2 - 38142448

AN - SCOPUS:85184073821

SN - 0006-4971

VL - 143

SP - 1646

EP - 1655

JO - Blood

JF - Blood

IS - 16

ER -

Association between elevated white blood cell counts and thrombotic events in polycythemia vera: analysis from REVEAL

Abstract

Funding

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this