Hct ≥45% and WBC counts >11 × 109/L put patients at increased risk of thrombosis1,2
In the CYTO-PV study,
Hct levels ≥45% carry a serious risk in PV1
Elevated Hct between 45% and 50%: 4-fold higher rate of cardiovascular death and major thrombosis1
- A significant increase in the risk of cardiovascular death and major thrombosis was demonstrated with Hct levels between 45% and 50% compared with Hct levels of <45% (HR, 3.91; 95% CI, 1.45-10.53; P=0.007)1*
Probability of Remaining Event-Free in the CYTO-PV Study (N=365)1
Kaplan-Meier curves for composite primary endpoint.
From The New England Journal of Medicine, Marchioli R, Finazzi G, Specchia G, et al; for the CYTO-PV Collaborative Group, Cardiovascular events and intensity of treatment in polycythemia vera, 368, Pages 22-33. © 2013 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.
*In the CYTO-PV study of 365 adult patients with PV treated with PBT, HU, or both, patients were randomized to 1 of 2 groups: the low-Hct group (n=182; with more intensive therapy to maintain a target Hct level <45%) or the high-Hct group (n=183; with less intensive therapy to maintain a target Hct level of 45% to 50%). Baseline characteristics were balanced between the groups. Approximately 50% of patients had received an initial diagnosis of PV within 2 years prior to randomization. 67.1% of patients (n=245) were at high risk because they were ≥65 years of age or had experienced previous thrombosis. The composite primary endpoint was the time until cardiovascular death or major thrombosis.1
In the MPN Practice Perspectives Survey (N=1550),†
of hematologists/oncologists allow a maximum Hct level >45% before changing treatment
†1550 practicing hematologists/oncologists across the United States participated in the MPN Practice Perspectives Survey and provided comprehensive insights that could inform best practices to optimize the management of patients with MPN.
Find out why Jamile M. Shammo, MD, FASCP, FACP, believes even a slight increase in Hct levels can substantially impact patients
Monitoring WBC counts is critical to managing for the risk of thrombosis2
In an additional analysis from the CYTO-PV study,
Elevated WBC counts >11×109/L increased the risk of thrombosis2
- In a multivariable, time-dependent analysis, WBC counts >11 × 109/L were associated with an increased risk of thrombosis (HR, 3.9; 95% CI, 1.24-12.3; P=0.02)2
Time-Dependent Multivariable Analysis of the Risk of Major Thrombosis in the CYTO-PV Study (N=365)2,a
aAdjusted for age, gender, cardiovascular risk factors, previous thrombosis, and Hct levels.2
- In this analysis, there was a trend for increased risk of thrombosis with WBC count >7 × 109/L (ie, HR >1) that became statistically significant in patients with WBC counts >11 × 109/L2
- These results are consistent with other literature that suggests leukocytosis may increase the risk of thrombosis3,4
of hematologists/oncologists allow WBC counts >11 × 109/L when managing for the risk of thrombosis
In my practice, when a patient shows a progressive increase in WBC counts above 11 × 109/L, that is an indicator that my patient needs a change in treatment.
Raajit Rampal, MD, PhD, MPN Expert
In the prospective, observational, REVEAL study,‡
The estimated 4-year mortality rate was 14% in patients with high-risk PV5§
- 86% of high-risk patients (1660/1940) received HU and/or PBT at enrollment6
Overall Survival by Risk Category at Enrollment in the REVEAL Study5
Reprinted from 62nd ASH Annual Meeting and Exposition; December 5-8, 2020. Abstract 484, Stein BL, Patel K, Scherber RM, Yu J, Paranagama D, Miller CB, Mortality and causes of death in patients with polycythemia vera: analysis of the REVEAL prospective, observational study, Page 1, © 2020, with permission from American Society of Hematology.
In the 6 months before death,5
(110/190) of patients had ≥1 elevated WBC count >11 × 109/L||
(59/190) of patients had ≥1 elevated Hct level >45%
‡REVEAL was a prospective, observational study of 2510 adult patients with PV in the United States, sponsored by Incyte. Patients were enrolled over an approximate 2-year period (July 2014 to August 2016). This analysis included all enrolled patients and evaluated characteristics of deceased patients, survival by risk, and causes of death over the course of the study. A total of 244 patients died during the study, with 190 having available Hct levels and WBC counts in the 6 months before death, and 175 having a known cause of death. Among the 244 patients who died during the study, 82% (n=200) were categorized as high risk at diagnosis, primarily because they were ≥60 years of age only (65%; n=159).5
§77% of patients (1940/2510) were classified as high risk at enrollment based on being 60 years of age or older and/or having a history of thrombotic events.5,6
||71% (78/110) of these patients did not experience an infection in the year prior to death.7
In the REVEAL study,¶
Some patients continued to have elevated blood counts despite treatment with HU alone and HU plus PBT4,8
Elevated Laboratory Values in Patients Who Received HU for ≥3 Months in the REVEAL Study4,8
Analysis included patients with all 3 laboratory values.8
From Clinical Lymphoma, Myeloma & Leukemia, 20(4), Grunwald MR, Kuter DJ, Altomare I, et al, Treatment patterns and blood counts in patients with polycythemia vera treated with hydroxyurea in the United States: an analysis from the REVEAL study, Pages 219-225, © 2019, with permission from Elsevier.
¶This analysis focused on blood count control in the subset of 1381 patients who had received HU for ≥3 months.4
In the REVEAL study,
Patients who were treated with HU and receiving PBT were more likely to have elevated blood counts8
The median of the maximum Hct level among evaluable patients (n=1106) who received HU for ≥3 months was 48% for those who reported a level of >45% and 42% for those who reported a level ≤45%8
Elevated Laboratory Values by PBT Within 3 Months of Enrollment and HU Exposure8
After 3 months of HU, 33% (457/1381) of patients continued to undergo PBTs4
Of 457 evaluable patients who received a PBT after 3 months of HU, 82.9% continued to have Hct >45%4
CI=confidence interval; CYTO-PV=Cytoreductive Therapy in Polycythemia Vera; Hct=hematocrit; HR=hazard ratio; HU=hydroxyurea; MPN=myeloproliferative neoplasm; PBT=phlebotomy; PLT=platelet; PV=polycythemia vera; REVEAL=pRospective obsErvational study of patients with polycythemia VEra in US clinicAL practices; WBC=white blood cell.
References: 1. Marchioli R, Finazzi G, Specchia G, et al; for CYTO-PV Collaborative Group. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med. 2013;368(1):22-33. 2. Barbui T, Masciulli A, Marfisi MR, et al. White blood cell counts and thrombosis in polycythemia vera: a subanalysis of the CYTO-PV study. Blood. 2015;126(4):560-561. 3. Gangat N, Strand J, Li CY, Wu W, Pardanani A, Tefferi A. Leucocytosis in polycythaemia vera predicts both inferior survival and leukaemic transformation. Br J Haematol. 2007;138(3):354-358. 4. Grunwald MR, Kuter DJ, Altomare I, et al. Treatment patterns and blood counts in patients with polycythemia vera treated with hydroxyurea in the United States: an analysis from the REVEAL study. Clin Lymphoma Myeloma Leuk. 2020;20(4):219-225. 5. Stein B, Patel K, Scherber RM, Yu J, Paranagama D, Miller CB. Mortality and causes of death in patients with polycythemia vera: analysis of the REVEAL prospective, observational study. In: 62nd ASH Annual Meeting and Exposition; December 5-8, 2020. Abstract 484. 6. Grunwald MR, Stein BL, Boccia RV, et al. Clinical and disease characteristics from REVEAL at time of enrollment (baseline): prospective observational study of patients with polycythemia vera in the United States. Clin Lymphoma Myeloma Leuk. 2018;18(12):788-795. 7. Data on file. Incyte Corporation. Wilmington, DE. 8. Grunwald MR, Altomare I, Burke JM, et al. Examining the patterns and blood counts among patients with polycythemia vera treated with hydroxyurea in the United States: an analysis from the REVEAL study. Poster presented at: 59th American Society of Hematology Annual Meeting and Exposition, 2017; December 9-12, 2017; Atlanta, GA.