Open Access

Patterns of hydroxyurea use and clinical outcomes among patients with polycythemia vera in real-world clinical practice: a chart review

  • Shreekant Parasuraman1Email author,
  • Marco DiBonaventura2,
  • Kelly Reith1,
  • Ahmad Naim1,
  • Kristen Concialdi2 and
  • Nicholas J. Sarlis1
Experimental Hematology & Oncology20165:3

DOI: 10.1186/s40164-016-0031-8

Received: 24 September 2015

Accepted: 4 January 2016

Published: 1 February 2016

Abstract

Background

Hydroxyurea (HU) is among the most commonly used cytoreductive treatments for polycythemia vera (PV), but previous research and clinical experience suggest that not all patients respond optimally, consistently, or durably to HU treatment. This study investigated patterns of HU use and impact on disease control among patients with PV in real-world clinical practice in the United States.

Methods

Oncologists and hematologists recruited between April and July 2014 reported data from patient charts. Treatment history and disease symptom comparisons between HU subgroups were performed using Chi square tests or one-way analyses of variance for categorical and continuous variables. Other analyses were performed using descriptive statistics.

Results

Overall, 329 physicians participated and provided data on 1309 patients with PV (62.3 % male; mean age = 62.5 years, mean time since diagnosis = 5.2 years). In the 229 (17.5 %) patients who had stopped HU, the most common reasons for HU discontinuation—as assessed by the treating clinician—were inadequate response (29.3 %), intolerance (27.5 %), and disease progression (12.7 %). Among patients currently on HU, a significant proportion had elevated blood cell counts: 34.4 % had hematocrit values ≥45 %, 59.4 % had platelet levels >400 × 109/L, and 58.2 % had WBC counts > 10 × 109/L. Two-thirds (66.3 %) of patients had ≥1 elevated count, 40.3 % had ≥2 elevated counts, and 19.8 % had all 3 counts elevated. The most common PV-related signs and symptoms among all patients were fatigue and splenomegaly.

Conclusions

Although many patients with PV benefit from HU therapy, some continue to have suboptimal control of their disease, as evidenced by persistence of abnormally elevated blood cell counts and the continued experience of disease-related manifestations (signs and symptoms). These data further denote a significant medical need for some patients with PV currently or previously treated with HU.

Keywords

Polycythemia vera Chart review Hydroxyurea

Background

Polycythemia vera (PV) is a progressive, chronic myeloproliferative neoplasm characterized by a primary, clonally-driven abnormal increase in red cell mass and elevations in platelet and white blood cell (WBC) counts [1]. The 2008 World Health Organization major diagnostic criteria for PV require erythrocytosis (i.e., elevated hemoglobin, hematocrit, red cell mass levels) or an activating mutation in JAK2; minor diagnostic criteria include bone marrow trilineage myeloproliferation, subnormal serum erythropoietin level, and endogenous erythroid colony growth [2]. A confirmed diagnosis per these criteria requires a patient to meet either (1) both major criteria and 1 minor criterion or (2) the first major criterion (i.e., erythrocytosis) and 2 minor criteria. There are over 100,000 patients with PV in the United States [3]. The condition is associated with an elevated risk of thrombosis (both arterial and venous), which is one of the most common causes of death in patients with PV [4]. As the disease progresses, a number of other hematologic complications may evolve, including secondary acute myeloid leukemia, myelodysplastic syndrome, and post-PV myelofibrosis [4, 5]. Although presentation is most common at 60 years of age or older [4, 6], one-third of PV cases occur in patients younger than age 50 [4].

Treatment of PV is aimed at the prevention of thrombotic events [1], and typical frontline management includes a combination of low-dose aspirin and phlebotomy (PBT) to decrease hematocrit (Hct) to <45 % [7, 8]. Management of WBC counts and platelet levels are also important treatment goals [9]. Underscoring the importance of careful management of PV, a study by Marchioli et al. found that treating to a higher Hct target range of 45–50 % versus stringently maintaining a Hct of <45 % was associated with a fourfold increase in death from cardiovascular causes or major thrombosis after a median follow-up of 31 months [7].

Some patients with PV require cytoreductive therapy to achieve target Hct levels [10] and to normalize WBC and platelet counts per European LeukemiaNet (ELN) response criteria [11]. Ruxolitinib is the only agent with regulatory approval for use in the PV setting, indicated by the US Food and Drug Administration for patients with PV who have had an inadequate response to or are intolerant of hydroxyurea (HU; also known as hydroxycarbamide) [12] and by the European Medicines Agency for the treatment of adult patients with PV who are resistant to or intolerant of HU [13]. Interferon-α is used to treat some patients with PV [10] and additional options are currently in development (e.g., other JAK2 inhibitors [14, 15], histone deacetylase inhibitors [16, 17]). Although not approved by regulatory agencies for the treatment of PV, HU is the most commonly used cytoreductive agent in the PV setting [1]. HU can be clinically efficacious; however, some patients may not receive adequate benefit or may not tolerate long-term therapy [18]. Indeed, a study by Alvarez-Larrán et al. found that 12 and 13 % of patients with PV had resistance and intolerance to HU, respectively, with the former significantly associated with an increased risk of death [18]. Thus, about one in four patients with PV who receive treatment with HU fall short of treatment goals. In real-world clinical practice, HU resistance is often secondary (i.e., develops over time). Indeed, the treatment patterns for high-risk patients with PV or those whose disease advances over time can sometimes evolve toward the combined use of HU and PBT. In the latter case, patients whose disease had been adequately controlled by HU end up needing more aggressive management, thus forcing the treating clinician to reintroduce PBT to the ongoing cytoreductive therapy to achieve control of blood cell counts and/or control of disease-related symptom burden [1, 19].

Although several studies have examined PV and its treatment in European populations [7, 18], none to our knowledge have studied the effectiveness and limitations of HU in clinical practice in the United States. Using a retrospective chart review method, this study investigated patterns of HU use and the impact of HU on the signs, symptoms, and complications of PV in a real-world US population.

Results

Physicians and patients

A total of 329 physicians participated, with the majority (78.1 %) being hematologist-oncologists (Table 1). These physicians provided information on 1309 patients (Table 2). The majority of patients were men (62.3 %); overall, the mean (SD) age was 62.5 (12.2) years and mean (SD) time from PV diagnosis was 5.2 (2.8) years.
Table 1

Demographic characteristics of the survey-participating physicians

 

Total physician sample (N = 329)

Sex, n (%)

 

 Male

256 (77.8)

 Female

51 (15.5)

 Decline to provide

22 (6.7)

Years of age, n (%)

 

 <35

11 (3.3)

 35‒44

118 (35.9)

 45‒54

105 (31.9)

 55‒64

70 (21.3)

 >65

6 (1.8)

 Prefer not to state

19 (5.8)

Office location, n (%)

 

 Major metropolitan area, population >500,000

116 (35.3)

 Urban area, population between 100,000 and 500,000

98 (29.8)

 Suburb of a large city, population >100,000

73 (22.2)

 Small city, population between 30,000 and 100,000

22 (6.7)

 Rural or small town, population <30,000

20 (6.1)

Practice type, n (%)

 

 Solo practice

23 (7.0)

 Single-specialty group practice

189 (57.4)

 Multi-specialty group practice

117 (35.6)

Self-reported medical specialty, n (%)

 

 Hematology

21 (6.4)

 Oncology (medical oncologist)

51 (15.5)

 Hematology-oncology

257 (78.1)

Years practicing

 

 Mean ± SD

13.8 ± 6.8

Number of patients with PV under care in past 12 mo

 

 Mean ± SD

55.1 ± 75.2

PV polycythemia vera

Table 2

Demographic and health history characteristics of patients in retrieved medical charts

 

Total patient sample (N = 1309)

Years of age

 

 Mean ± SD

62.5 ± 12.2

Sex, n (%)

 

 Male

816 (62.3)

 Female

493 (37.7)

BMI

 

 Mean ± SD

25.9 ± 4.6

Deceased, n (%)

 

 No

1291 (98.6)

 Yes

18 (1.4)

Race/ethnicity, n (%)

 

 Non-Hispanic white

864 (66.0)

 Non-Hispanic black

171 (13.1)

 Hispanic

161 (12.3)

 Multiracial/other

82 (6.3)

 Unknown race/ethnicity

31 (2.4)

Employment status, n (%)

 

 Employed

496 (37.9)

 Retired/unemployed

629 (48.1)

 On disability

59 (4.5)

 Unknown

125 (9.6)

Insurance status, n (%)

 

 Private insurance

562 (42.9)

 Medicare

500 (38.2)

 Medicaid

126 (9.6)

 VA

36 (2.8)

 State health exchange

33 (2.5)

 Uninsured

27 (2.1)

 TRICARE

16 (1.2)

 Unknown

106 (8.1)

Charlson comorbidity index

 

 Mean ± SD

0.6 ± 0.8

Number of treated comorbidities

 

 Mean ± SD

1.6 ± 1.2

BMI body mass index, VA veterans affairs

Hydroxyurea treatment patterns

A total of 1080 (82.5 %) patients were still using HU at the time of chart abstraction, whereas 229 (17.5 %) had discontinued HU. Reasons for discontinuation were related to inadequate response (abnormally elevated Hct, hemoglobin, or platelet counts; 29.3 %), HU intolerance (i.e., adverse effects; 27.5 %), or disease progression (fibrotic stage PV, persistent thrombocytopenia; 12.7 %); each individual patient could be assigned ≥1 reason for discontinuation (Fig. 1).
Fig. 1

Reasons for HU discontinuation (n = 229). HU hydroxyurea, WBC white blood cell. Please note that these reasons were not mutually exclusive, and the sum of the percentages is greater than 100 %

As shown in Table 3, the mean daily dose of HU was similar in patients currently and previously treated with HU (approximately 1 g); the highest, lowest, and most stable HU doses were also similar between groups. Mean (SD) duration of HU use was 47.0 (30.8) months among patients currently using HU (31.4 % had been on HU for at least 1 year) and 23.2 (24.5) months among those who had discontinued HU. Among patients who discontinued HU, the mean (SD) time since HU discontinuation was 20.2 (26.4) months.
Table 3

HU-related treatment patterns associated with patients who discontinued and those who did not

 

Currently using HU therapy (n = 1080)

Discontinued HU therapy (n = 229)

Years diagnosed with PV

  

 n

1080

229

 Mean ± SD

5.23 ± 2.77

5.25 ± 2.82

Duration of HU therapy for current users, mo

  

 n

1080

 Mean ± SD

46.97 ± 30.83

Duration of HU therapy before discontinuation, mo

  

 n

229

 Mean ± SD

23.19 ± 24.45

Current HU dose, mg/d

  

 n

1055

 Mean ± SD

984.2 ± 673.6

 Median (q25–q75)

1000.0 (500.0–1000.0)

Last dose of HU before discontinuation, mg/d

  

 n

225

 Mean ± SD

990.9 ± 689.3

 Median (q25–q75)

1000.0 (500.0–1200.0)

Highest ever HU dose, mg/d

  

 n

491

123

 Mean ± SD

1413.0 ± 875.5

1443.6 ± 876.4

 Median (q25–q75)

1000.0 (1000.0–2000.0)

1000.0 (1000.0–2000.0)

Lowest ever HU dose, mg/d

  

 n

503

125

 Mean ± SD

745.1 ± 576.8

744.0 ± 437.9

 Median (q25–q75)

500.0 (500.0–1000.0)

500.0 (500.0–1000.0)

Most stable HU dose, mg/d

  

 n

468

114

 Mean ± SD

1129.8 ± 742.2

1167.2 ± 781.7

 Median (q25–q75)

1000.0 (712.5–1500.0)

1000.0 (500.0–1500.0)

Number of HU dose adjustments in 3 mo before discontinuation

  

 n

205

 Mean ± SD

0.48 ± 1.06

HU hydroxyurea, PV polycythemia vera

Clinicohematologic response while on hydroxyurea

Although patients currently on HU had been treated with HU for a mean (SD) of 47.0 (30.8) months, a notable proportion had elevated blood cell counts above response thresholds: 34.4 % had Hct levels ≥45 % , 58.2 % had WBC counts >10 × 109/L, and 59.4 % had platelet counts >400 × 109/L (Fig. 2). Two-thirds (66.3 %) of these patients had ≥1 elevated value, 40.3 % had ≥2 elevated values, and 19.8 % had all 3 values elevated (Fig. 3). Only 37.1 % of patients currently on HU had achieved a complete response (CR) per European LeukemiaNet (ELN) criteria; 41.6 % had achieved a partial response (PR), whereas 21.3 % had no response; this was significantly different than patients who had discontinued HU (19.7, 52.0, 28.4 % of whom had a CR, PR, and no response, respectively; P < 0.05) (Fig. 4). Furthermore, a relationship did not appear to exist between HU dose and CR or PR status (Fig. 5), although the disease severity may have been worse among patients receiving more intense HU dose regimens.
Fig. 2

Most recent laboratory values among patients currently using HU (n = 1080). Hct hematocrit, HU hydroxyurea, WBC white blood cell. Hct ≥45 %, WBC counts >10 × 109/L, and platelet counts >400 × 109/L, were all considered elevated values for patients with PV

Fig. 3

Percentage of patients currently using HU (n = 1080) with different combinations of elevated laboratory values. Hct hematocrit, HU hydroxyurea, WBC white blood cell. Hct ≥45 %, WBC counts >10 × 109/L, and platelet counts >400 × 109/L, were all considered elevated values for patients with PV

Fig. 4

Distribution of CHR status among patients currently receiving HU and patients who discontinued HU. ELN European LeukemiaNet, HU hydroxyurea. CHR status was determined per ELN response criteria. ELN response criteria are based on the following: levels of Hct, platelet count, WBC count, spleen size, and disease symptoms (pruritus, angina, headache) [9]

Fig. 5

Distributions of the lowest, highest, most stable, and current HU doses with corresponding response rates. CR complete response, PR partial response

Polycythemia vera‒related signs and symptoms

The most commonly observed PV-related signs and symptoms ever experienced among all patients were fatigue (62.8 %) and splenomegaly (58.3 %). The prevalence of PV-related signs, symptoms, and events in the past 12 months were summarized in 2 HU therapy-defined subgroups: (1) since starting HU therapy among patients currently using HU and (2) in the past 12 months among patients who discontinued HU. Several symptoms were significantly more common among patients still using HU therapy versus those who had discontinued HU (P < 0.05; Table 4), including dizziness (10.4 vs 17.9 %), abdominal discomfort (9.8 vs 17.0 %), and bone pain (4.0 vs 7.0 %).
Table 4

Incidence of signs, symptoms, and events in the past 12 months

Sign, symptom, or event, n (%)

Currently using HU therapy (n = 1080)

Discontinued HU therapy (n = 229)

Fatigue or tiredness

304 (28.1)

74 (32.3)

Splenomegaly

267 (24.7)

60 (26.2)

Plethora

138 (12.8)

27 (11.8)

Dizziness

112 (10.4)

41 (17.9)*

Headache

108 (10.0)

23 (10.0)

Abdominal discomfort/pain

106 (9.8)

39 (17.0)*

Hepatomegaly

103 (9.5)

27 (11.8)

Pruritus

96 (8.9)

23 (10.0)

Feeling of fullness

89 (8.2)

28 (12.2)

Thrombotic eventsa

64 (5.9)

11 (4.8)

Cardiovascular problems

52 (4.8)

14 (6.1)

Bone pain

43 (4.0)

16 (7.0)*

Anemia

28 (2.6)

13 (5.7)*

Thrombophlebitis

24 (2.2)

3 (1.3)

Thrombosis

22 (2.0)

2 (0.9)

Neutropenia

21 (1.9)

3 (1.3)

Thrombocytopenia

14 (1.3)

4 (1.8)

Stroke/TIA

18 (1.7)

5 (2.2)

Pulmonary embolism

7 (0.6)

1 (0.4)

Cancer

5 (0.5)

0

Elevation in blasts

2 (2.1)

4 (1.8)

Unknown

21 (1.9)

12 (5.2)*

No new symptoms

471 (43.6)

91 (39.7)

HU hydroxyurea, TIA transient ischemic attack

Values in italics identify signs, symptoms, or events that were significantly (P < 0.05) different between patients currently using HU therapy and those who discontinued HU therapy

* P0.05

aIncludes all patients who experienced pulmonary embolism, stroke/TIA, thrombophlebitis, and/or thrombosis; patients may have experienced more than 1 thrombotic event

Discussion

Patients with PV experience a significant disease burden that can interfere with their quality of life and ability to engage in daily activities [20, 21]. Patients are also at significant increased risk for morbidity and mortality, including the risk for thromboembolic events [4, 22]. Despite the established importance of maintaining Hct levels <45 % using traditional treatment approaches such as HU cytoreduction to avoid these adverse outcomes, more than one-fourth of patients do not achieve this Hct target [7, 8]. The current report examines real-world treatment patterns among a large, representative sample of patients with PV currently or previously treated with HU across multiple treatment centers in the US.

Nearly one-fifth of patients in this study discontinued HU therapy, mostly because of a lack of response or safety/tolerability. Using our definition of response (based on applying published ELN criteria to the data collected in this study [9]), approximately 80 % of patients achieved either a CR or PR while on HU treatment. These results suggest that while many patients derive benefit with HU, there is a substantial subset of patients (including patients on HU who had no response and patients who discontinued HU), whose disease remains suboptimally controlled with HU in every-day clinical practice. This is important because the need for HU therapy itself arises when PBT alone becomes inadequate to manage blood cell counts. Indeed, in our cohort, in which all patients were treated with HU for ≥2 months, a large proportion of patients experienced Hct levels above the recommended threshold of 45 %. It is highly likely that such patients required combined therapy with PBT and continued HU. Moreover, the majority of HU users had elevated WBC or platelet counts; the latter, of course, are typically not influenced by the addition of PBT to HU treatment, which further exemplifies the pragmatic management challenges associated with this setting. Evidence suggests that patients with elevated Hct or elevated WBC count are at a significantly higher risk for cardiovascular morbidity and mortality [4, 7]. Patients treated to a higher Hct target range of 45–50 % had 4 times the rate of death from cardiovascular causes or major thrombosis versus patients who were strictly treated to a Hct target of <45 % [7]. Previously, Tefferi et al. identified a significant association between WBC count and subsequent survival [4]. More recently, analysis of data from the prospective Cytoreductive Therapy in Polycythemia Vera (CYTO-PV) trial demonstrated that risk of major thrombosis was approximately four times greater in patients with WBC counts ≥11 × 109/L versus <7×109/L (P = 0.02) [23], further highlighting the importance of proper disease control in patients with PV.

In this study, clinicohematologic response (CHR) rates did not correlate with HU dose, suggesting that at least some patients may be intrinsically resistant to HU. Further, more than 30 % of patients had received ≥2000 mg per day of HU as their highest dose, and more than 10 % of patients were being administered ≥2000 mg per day as their current dose, suggesting that even at these very high doses of HU patients do not achieve their treatment goals.

More than half of patients with PV experienced PV-related signs and symptoms after diagnosis, particularly fatigue and splenomegaly. Although the time frame and the method of assessment (physician-reported data from available chart information vs prospective validated patient-reported symptom assessments) were different in our study compared with past studies, the most frequent symptoms were similar (e.g., fatigue, splenomegaly, pruritus, headache, and abdominal pain) [21, 24, 25]. Additionally, Vannucchi et al. reported that the use of standard therapy (HU for the majority of patients) had little effect on reducing symptom scores in patients with PV; in fact, several symptom scores actually increased over a 32-week period in patients with PV treated with traditional therapies [24]. These findings reinforce the important unmet need of symptom control among many patients with PV.

Our study has various limitations consistent with the nature of a retrospective chart review. Patient charts were occasionally incomplete, leading to missing documentation of possible responses (e.g., unknown laboratory values) and potential post hoc interpretation by physicians (e.g., the presence of fatigue), which could have introduced error. In addition, HU dosing was captured at designated time frames, which may not reflect the complete, detailed evolution of a dosing regimen over time for a given patient. Also, although the sample source was demographically representative of the hematologist-oncologist population based on American Medical Association statistics, the patient charts selected may have differed from the overall population of patients across the US with respect to disease severity or the nature, duration, or intensity of applied treatments. Despite these limitations, this analysis provides a contemporary real-world assessment of the patterns of HU use and the corresponding impact on disease control in a large population of patients with PV from multiple academic and community practices across the US.

Conclusions

Consistent with other reports, this study demonstrates that HU has an important place and role in the treatment of PV in the US. However, a significant subset of patients continue to experience suboptimal control of their PV, as evidenced by persistent elevations in their blood cell counts and the continued presence of burdensome and unremitting disease-related symptoms. Based on our results, it is estimated that for up to a third of patients, PV may be or become suboptimally controlled by HU over the next 5 years. At the time of this study, physicians had few treatment alternatives to consider for PV that was inadequately controlled with HU, even with the concomitant addition of PBT. Therefore, these data further illustrate a significant medical need for a sizeable proportion of patients with PV either currently or previously treated with HU.

Methods

Survey development

Initial qualitative interviews were conducted with 19 oncologists, hematologists, and hematologist-oncologists to help inform the development of the chart review survey. A specific focus of these interviews was to understand how clinicians manage patients with PV and clinicians’ experiences with HU therapy. These consisted of 1-h individual in-person detailed interviews conducted by a trained moderator using a structured discussion guide.

Physician respondents

Physicians were recruited for this study between April and July 2014 to complete an online collation of data gathered from a retrospective chart review. Recruitment was conducted via email from a nationally-representative online panel of board-certified hematologists, oncologists, and hematologist-oncologists who had agreed to participate in blinded periodic research surveys. The recruitment of panel members was not solely based on convenience, as an attempt was made to match the characteristics of the broader population of the American Medical Association specialized in the treatment of cancer or blood disorders (see Additional file 1: Table S1). Physicians were eligible if they spent ≥50 % of their time on direct patient care and had ≥5 patients with PV under their care in the past 12 months, at least 25 % of whom had current or prior HU exposure. Physicians were compensated for their participation.

Patient charts

Participating physicians selected 4 charts for patients meeting the following criteria: age ≥18 years, alive at or deceased within the past 6 months from the time of chart abstraction, previously diagnosed with PV per physician judgement, with a disease duration of 3–15 years, having received HU therapy for ≥2 months within the last 5 years, having medical record data 12 months both before and after HU initiation, and having not been part of a PV-related clinical trial.

Chart review survey

Physicians entered all of their responses into an online data collection tool. This retrospective chart review first consisted of questions—completed by each physician in approximately 5 min—on general features of their clinical management of PV, along with demographic (e.g., age, sex) and practice information (e.g., specialty, years in practice, population density of catchment area, etc.).

Physicians then addressed questions regarding each patient. This information included patient demographics (e.g., age, sex, race/ethnicity, employment status, and insurance) and general health history information, such as body mass index and comorbidities.

PV-specific questions included the number of years since initial diagnosis and the various signs/symptoms (e.g., splenomegaly, fatigue), clinical events (e.g., stroke), qualitative laboratory anomalies (e.g., anemia, blast elevation), and discrete/measured laboratory test parameters (i.e., Hct, WBC counts, and platelet counts) that were present at 3 time-points for each patient: initial diagnosis, following the initiation of HU treatment, and during the past 12 months.

Physicians also answered several questions regarding HU treatment, including whether patients were still on HU or had discontinued HU (and how long ago), along with the highest, lowest, and most stable (the latter left up to the interpretation of the physician) doses of HU, if this information was available/retrievable. For patients still using HU, their current dose was reported, whereas for patients who had discontinued HU, their dose just prior to discontinuation was collected.

Clinicohematologic response

A CHR variable was determined for each patient. The CHR variable was modeled after the ELN definition [9] but was limited by the nature of the data collected in this study (e.g., absence of documentation of the duration of spleen/symptom resolution, absence of or poor documentation of the presence of hemorrhagic or thrombotic events over the follow-up period, and no availability of bone marrow serial specimens necessary to document histologic remission). Specifically, a CR in this analysis was defined as the combination of all the following target criteria being met: Hct <45 %, platelet count ≤400 × 109/L, WBC count ≤10 × 109/L, achievement of a normal spleen size (i.e., lack of an enlarged spleen as reported by the physician), and absence of disease-related symptoms (i.e., pruritus, fatigue, or headache). Patients who did not meet all of the criteria for a CR but had Hct <45 % without concomitant PBT or had a response in 3 or 4 of the 5 CR criteria previously mentioned were considered to have a PR. All others were considered to have no response.

Statistical analysis

Physician and patient demographics and health history were reported descriptively using means and standard deviations for continuous variables and frequencies and percentages for categorical variables. Treatment history and disease symptoms were compared between those who discontinued and those who were currently treated with HU using Chi square tests and one-way analyses of variance for categorical and continuous variables, respectively. CHR and the achievement of individual blood count target thresholds were reported descriptively (frequencies and percentages).

Ethics, consent, and permissions

The study was conducted in compliance with the Declaration of Helsinki. All study materials were reviewed and approved by an independent institutional review board (Sterling IRB [Atlanta, GA, USA]; protocol number, 161101176).

Abbreviations

CHR: 

clinicohematologic response

CR: 

complete response

ELN: 

European LeukemiaNet

Hct: 

hematocrit

HU: 

hydroxyurea

PBT: 

phlebotomy

PR: 

partial response

PV: 

polycythemia vera

WBC: 

white blood cell

Declarations

Authors’ contributions

SP, MD, KR, NJS, and KC designed the study and wrote the survey. KC was responsible for the recruitment and collection of data. MD was responsible for the data analysis. SP, MD, KR, NJS, and KC all participated in the data interpretation. MD drafted the initial version of the manuscript with editorial contributions from SP, KR, NJS, and KC. All authors read and approved the final manuscript.

Acknowledgements

Writing assistance was provided by Cory Pfeiffenberger, Ph.D. (Complete Healthcare Communications, LLC), whose work was funded by Incyte Corporation.

Competing interests

This study, associated data analysis, and preparation of this manuscript were carried out by Kantar Health, in a project funded by Incyte Corporation. S.P., K.R., and N.J.S. are full-time employees of Incyte Corporation. M.D. and K.C. are full-time employees of Kantar Health.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
Incyte Corporation
(2)
Kantar Health

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© Parasuraman et al. 2016

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