- Email: [email protected]
Management of Polycythemia Vera: A Survey of Canadian Physician Practice Patterns
Accepted Manuscript Management of Polycythemia Vera: A survey of Canadian Physician Practice Patterns Laura Anne Habib, Kevin H.M. Kuo, Tony Panzarella, Vikas Gupta, Martina Trinkaus PII:
S2152-2650(18)30239-8
DOI:
10.1016/j.clml.2018.07.297
Reference:
CLML 1185
To appear in:
Clinical Lymphoma, Myeloma and Leukemia
Received Date: 9 April 2018 Revised Date:
21 July 2018
Accepted Date: 27 July 2018
Please cite this article as: Habib LA, Kuo KHM, Panzarella T, Gupta V, Trinkaus M, Management of Polycythemia Vera: A survey of Canadian Physician Practice Patterns, Clinical Lymphoma, Myeloma and Leukemia (2018), doi: 10.1016/j.clml.2018.07.297. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Management of Polycythemia Vera: A survey of Canadian Physician Practice Patterns
RI PT
Laura Anne Habib1 Kevin H.M. Kuo1 Tony Panzarella2 Vikas Gupta2 Martina Trinkaus3 1
SC
Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada Address: 200 Elizabeth St, Toronto, ON M5G 2C4, Canada 2
M AN U
Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Canada Address: 610 University Ave, Toronto, ON M5G 2M9, Canada
3
Division of Hematology/Oncology, St. Michael’s Hospital, University of Toronto, Toronto, Canada Address: 30 Bond St, Toronto, ON M5B 1W8, Canada
AC C
EP
TE D
Corresponding author: Laura Anne Habib Email: [email protected] Address: 705-80 Wellesley street east, Toronto, ON, M4Y1H3, Canada
ACCEPTED MANUSCRIPT
Management of Polycythemia Vera: A survey of Canadian Physician Practice Patterns Habib L., Kuo K., Panzarella T., Gupta V., Trinkaus M. Micro Abstract:
RI PT
The literature is scarce about the clinical uptake of the 2016 World Health Organization (WHO) revised classification criteria for the diagnosis of polycythemia vera (PV). A survey of 86 Canadian practicing hematologists/oncologists revealed that heterogeneity exists in the diagnosis and practice of PV. Greater awareness of the diagnostic criteria and Canadian guidelines translates into recommended work up and management of PV patients.
SC
Abstract:
AC C
EP
TE D
M AN U
Background: The 2016 World Health Organization (WHO) revised classification criteria for the diagnosis of polycythemia vera (PV) allows for an earlier detection of masked PV. The literature is scarce about the clinical uptake of new diagnostic algorithms for PV. In a cohort of Canadian hematologists, we aimed to identify how the revised 2016 World Health Organization (WHO) diagnostic criteria of Polycythemia Vera (PV) are being incorporated into hematology practice, and if the treatment of PV is comparable to the approaches outlined by the Canadian Myeloproliferative Neoplasm (MPN) Group.[1] Methods: A cross-sectional survey of practicing Canadian hematologists/oncologists was distributed to active members of the Canadian Hematology Society (CHS) using an online survey-distributing website. Univariate and multivariate analysis was performed. Results: The survey was completed by 86 respondents in total. Only type of practice was associated with respondents offering aspirin to all PV patients (P=0.0009). Respondents who were aware of the Canadian MPN guidelines were more likely to phlebotomize patients to a target hematocrit of <45% irrespective of gender (P=0.042). Younger practitioners were more likely to use age over 60 as an indication for initiating cytoreductive therapy (P=0.0006). Most (85.3%) respondents would recommend indefinite anticoagulation in patients with PV who developed unprovoked venous thromboembolism. Conclusion: The survey confirmed that heterogeneity of practice in diagnosis and management of PV among Canadian hematologists exists, suggesting that targeted education in specific segments of the PV treatment providers may result in wider adoption of the guidelines and diagnostic criteria. Key words: Polycythemia Vera, myeloproliferative neoplasm, survey, management, diagnostic criteria Original Study: Introduction: PV is a stem cell disorder characterized by overproduction of red blood cells and may also result in thrombocytosis and leukocytosis.[2] It has an incidence rate of 1 case per 100 000 persons and
ACCEPTED MANUSCRIPT
a prevalence of 44-57 per 100 000 persons from recent North American data.[3, 4] The median age at presentation is 61 with a median survival of 18.9 years. [4, 5]
RI PT
The 2016 World Health Organization (WHO) revised classification criteria for the diagnosis of PV allows for an earlier detection of masked PV. [1] Changes in diagnosis include a lower hemoglobin threshold to a hemoglobin of >165 g/L [16.5g/dL] (160 g/L [16g/dL] in women) from >185 g/L (165 g/L in men), and inclusion of a bone marrow biopsy.[6] Patients with mPV may present with lower hemoglobin levels and have an increased risk of thrombosis potentially related to later diagnosis and treatment. [7, 8]
M AN U
SC
The Canadian MPN Group have outlined recommendations for management of PV. [1] These recommendations suggest that aspirin be given to all patients with PV unless contra-indicated and that patients undergo cardiovascular risk reduction. They further recommend strict hematocrit control (target hematocrit < 45% in men and women) and cytoreductive therapy for high risk patients (age of > 60 years old and/or prior thrombosis). A survey of 71 American hematologists prior to the revised 2016 WHO criteria found that despite the discovery of the JAK2 mutations, there remained significant variability in the treatment and diagnosis of PV. [9] No survey to date has been performed among Canadian physicians.
Methods:
TE D
We aimed to evaluate the impact of the revised 2016 WHO criteria for the diagnosis of PV among Canadian hematologists practicing in diverse settings. We also aimed to describe the management and treatment of PV among Canadian hematologists as they compare to the approaches outlined by the Canadian MPN Group [1] with the purpose to identify areas in which guidelines lack or should be reinforced, and areas in which education and research is needed.
AC C
EP
Health Sciences Research Ethics Board of the University of Toronto approval was granted in April 2017 for a cross sectional exploratory survey-based study of Canadian hematologist. Potential participants were captured primarily through membership with the Canadian Hematology Society (CHS) which had 299 active members at the time of survey distribution. Members comprised of physicians practicing in diverse settings. Status as a practicing hematologist was self- reported and consent was implied by participating in the survey. Participation was voluntary and anonymous. The survey comprised of 16 questions that characterized the demographics of our respondents and addressed their practice in diagnosis and management of PV. Survey design was adapted from the 2016 American survey published in the Journal of the National Comprehensive Cancer Network.[9] A pilot survey was performed at the Princess Margaret Hospital Myeloproliferative Neoplasm Rounds prior to distribution. The survey was distributed online in English and French using an online survey-distributing website, SurveyMonkey.com™. A reminder email was sent out two weeks following the original request. Each participant was asked to complete the survey only once. The only data available to investigators were survey responses and basic demographics. Three respondents completed the online French survey and 66 the English version. Paper copies of the survey were also distributed in English at the Leukemia Day
ACCEPTED MANUSCRIPT
conference in Toronto, April 6th, 2017, to members of CHS and 17 respondents returned paper copies of the survey.
RI PT
Descriptive statistics for quantitative data have been derived from all surveys completed by eligible participants. Categorical variables have been reported as percentages and normally distributed variables as means and standard deviations.
SC
Univariate analysis assessing age, sex, type of practice, practice setting and number of PV patients seen per year was performed on each of the diagnostic and management questions in the survey. Fisher’s exact test was used if the explanatory variable was categorical and the Wald chisquare test from a multiple logistic regression was used if the explanatory variable was continuous.
M AN U
Multivariable analysis assessing age, sex, type of practice, practice setting and number of PV patients seen per year was performed in relation to awareness of the WHO 2016 guidelines or the Canadian MPN guidelines. Logistic regression using the penalized maximum likelihood method was used to test the joint significance of explanatory variables on outcome. Penalized likelihood is a general approach to reducing small-sample bias in maximum likelihood estimation. A P value less than 0.05 was considered significant given the numerous outcomes and the large number of tests conducted in this exploratory analysis. All analyses were conducted using SAS version 9.4. Results:
EP
TE D
86 respondents completed the survey in total, (69 online surveys and 17 with paper copies). Table 1 describes the respondents’ characteristics, diagnosis and treatment approach. The mean number of patients seen by respondents annually was 22.6 (SD 23.6) and a median of 15 (range of 0-120). 52.4% were aware of the WHO 2016 PV diagnostic criteria while 41.5% were additionally aware of the Canadian MPN guidelines (6.1% were aware of neither). No variable significantly correlated with awareness of the WHO 2016 diagnostic criteria nor the Canadian MPN guidelines on univariate analysis.
AC C
37% of respondents would request a bone marrow biopsy to confirm the diagnosis of PV in JAK2 positive patients. Type of practice was associated with respondents offering aspirin to all PV patients without contra-indications to anti-platelet therapy (P=0.0009) on univariate analysis, while practice setting or number of PV patients seen per year did not. Respondents who were aware of the Canadian MPN guidelines were more likely to phlebotomize patients to a target hematocrit of <45% irrespective of gender (P=0.042). Younger practitioners were more likely to use age over 60 as an indication for initiating cytoreductive therapy which was independent of other confounders in the multivariable analysis (P=0.0006). All respondents chose hydroxyurea as their preferred first line cytoreductive agent. Most (85.3%) respondents would recommend indefinite anticoagulation in patients with PV who developed unprovoked venous thromboembolism (in whom there were no contraindications to anticoagulation). Respondents who saw more PV patients yearly were more likely to use a formal symptom assessment score
ACCEPTED MANUSCRIPT
such as the MPN10 score or the Edmonton Symptom Assessment System (ESAS) on univariate analysis (P=0.015).
RI PT
While 19% of respondents did not have JAK2 exon 12 testing available at their centers, 75% of respondents would request it for all their patients. Respondents who see more PV patients annually were more likely to request JAK2 exon 12 testing on all their patients which was independent of other confounders on multivariable analysis (P=0.032). Discussion:
SC
This survey confirmed that heterogeneity of practice in diagnosis and management of PV among Canadian hematologists persists despite the revised 2016 WHO diagnostic criteria and the guidelines set forth by the Canadian MPN group.
M AN U
Just over one third of our respondents would request a bone marrow biopsy to confirm the diagnosis of PV despite its addition to the revised 2016 WHO criteria. The Canadian MPN Group guidelines differ from the WHO criteria in that they suggest a diagnosis of PV can be made without a bone marrow biopsy if there is presence of elevated red blood cell volume as per the 2008 WHO criteria. [1]
EP
TE D
Our study is limited by a 29% response rate (86/299) and most respondents identifying their practice setting as academic (77.1%). Data regarding the breakdown of the practice setting of members within the CHS is unavailable for comparison. This contrasts with the survey conducted by Kander et al., 2016, which reported a 7.8% response rate from the MPN Research Foundation Database (N=847). Physicians with greater clinical experience or those working in private clinics had a greater tendency to use JAK2 molecular testing as a preferred diagnostic test. Nearly half of their respondents continued to use a sex-dependent hematocrit goal rather than a target hematocrit of 45% regardless of gender. Physicians in academic practice were more likely to recommend aspirin to their PV patients. Similar to our results, hydroxyurea was the preferred cytoreductive agent among 82% of respondents.[9]
AC C
Data from the national Swedish Cancer Registry including 9384 patients with MPN (PV=4389) followed between 1973-2009 demonstrated moderately reduced (36% lower) life expectancy in patients with PV when compared to the general population.[10] First line cytoreductive agents used in this cohort included hydroxyurea and radioactive phosphorus as per national guidelines at the time. An improvement in survival was observe in PV patients over time. This was attributed to prevention of thromboembolic events following the introduction of aspirin prophylaxis and phlebotomy titrated to target hematocrit. Results of a survey of 73 hematologists in 2014 demonstrated a lack of consensus for the treatment of thromboembolic complications in patients with an MPN.[11] Canadian hematologists appear to be less heterogeneous as 85.3% of our respondents would recommend indefinite anticoagulation for unprovoked venous thromboembolism in patients with PV. Clinical trials are lacking in this area. Older age has been shown to be a risk factor for thrombotic complications, transformation to AML and poorer overall survival in large cohort studies.[12, 13] Physicians in our survey were more likely to initiate cytoreduction in patients over the age of 60. As the age of providers
ACCEPTED MANUSCRIPT
M AN U
SC
RI PT
changes so too might the age at which patients may be recognized to have PV particularly as the revised WHO classification criteria allows for an earlier detection of masked PV. The preferred cytoreductive agent of choice by our respondents was hydroxyurea. Less is known regarding which younger patients warrant cytoreduction and which agent to use. Patients less than 40 years of age constitute 2.2-6.6% of yearly MPN cases in the United States.[5] Our survey did not address the distribution of the age of patients with PV. A retrospective study comparing patients with PV less than 45 years old to those older than 65 years old (n=204 patients; n=120 <45 years old) showed comparable rates of thrombotic complications aside from an increased rate of splanchnic vein thrombosis (13% vs 2%, p=0.0056).[14] Transformation to acute myeloid leukemia or myelofibrosis occurred at similar rates. While complications from PV similarly affect the younger population, thrombotic and transformational events were not predicted by younger age in a recent retrospective MPN cohort study including 37 adolescent and young adult patients (16-39 years old) with PV (total n= 2206).[15] Expert opinion recommends a risk adapted approach in asymptomatic young adult patients with PV offering aspirin prophylaxis with phlebotomy titrated to a hematocrit below 45% in the low risk population.[16] Cytoreductive therapy is recommended to the high-risk group. Hydroxyurea remains the first choice cytoreductive agent in patients who have experienced a life-threatening thrombotic event. While no robust data supports the theory of leukomogenicity of hydroxyurea, interferon-alpha and the pegylated form are considered alternative first line options.[16] Long term anticoagulation is recommended for unprovoked thromboembolism including splanchnic vein thrombosis and Budd-Chiari syndrome.[16]
EP
Clinical Practice Points:
TE D
Our survey results indicate that awareness of the guidelines and the updated diagnostic criteria translated into adopting approaches advocated in these documents. Only 42% of our respondents were aware of the Canadian MPN Group guidelines in addition to the 2016 revised WHO diagnostic criteria. This suggests that targeted education in specific segments of the PV treatment providers in Canada may result in wider adoption of the guidelines and diagnostic criteria.
AC C
The 2016 World Health Organization (WHO) revised classification criteria for the diagnosis of polycythemia vera (PV) allows for an earlier detection of masked PV. The literature is scarce about the clinical uptake of new diagnostic algorithms for PV. A cross-sectional survey of Canadian hematologists/oncologists was distributed to identify how these newly revised WHO criteria are being incorporated into hematology practice and to determine if treatment of PV is comparable to the approaches outlined by the Canadian Myeloproliferative Neoplasm (MPN) Group. 86 respondents completed the survey. Only type of practice was associated with respondents offering aspirin to all PV patients (P=0.0009). Respondents who were aware of the Canadian MPN guidelines were more likely to phlebotomize patients to a target hematocrit of <45% irrespective of gender (P=0.042). Younger practitioners were more likely to use age over 60 as an indication for initiating cytoreductive therapy (P=0.0006). Most (85.3%) respondents would recommend indefinite anticoagulation in patients with PV who developed unprovoked venous thromboembolism. Results revealed that heterogeneity exists in the diagnosis and practice of PV among Canadian hematologists despite the revised 2016 WHO diagnostic criteria and the guidelines set forth by the Canadian MPN group. Greater awareness of guidelines and
ACCEPTED MANUSCRIPT
updated diagnostic criteria translates into recommended work up and management of PV patients. Targeted education of PV criteria may improve adoption of the diagnostic criteria and management guidelines.
AC C
EP
TE D
Table 1. Respondent characteristics
M AN U
SC
RI PT
Appendix:
Table 2. Respondent management practices
AC C
EP
TE D
M AN U
Table 3. Univariate and multivariate analysis
SC
RI PT
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT
Survey Questionnaire: Demographics:
Diagnosis of Polycythemia Vera (PV):
M AN U
SC
RI PT
1. Please indicate your age: __________________________________________________________ 2. Please indicate your gender: a. Female b. Male 3. Your practice is primarily: a. Non-malignant hematology b. Malignant hematology c. Medical oncology d. Other (please specify): ____________________________________________________ 4. Your practice is in which of the following settings: a. Academic b. Community c. Other (please specify): _____________________________________________________ 5. Please indicate on average how many patients with PV do you see in a year: ________________
AC C
EP
TE D
6. Are you aware of the following: a. WHO 2016 PV diagnostic criteria b. Canadian MPN Guidelines c. Both d. Neither (please specify any other guidelines you may be aware of): _______________ 7. If a 65-year-old female with a hemoglobin of 165 g/L (16.5g/dL) is referred to you who is JAK2 V617F positive with a low erythropoeitin level, would you (chose all that apply): a. Consider her to have PV b. Request a bone marrow biopsy to confirm a myeloproliferative disorder c. Ensure other etiologies for an erythrocytosis are ruled out d. Order Calreticulin molecular testing to assist in prognostication of the patient’s myeloproliferative disorder 8. Under what circumstance would you perform a bone marrow biopsy in polycythemia vera? a. All cases at diagnosis including those who are JAK2 positive b. Those who are JAK2 V617F negative c. Other (please specify): _________________________________________________ 9. Do you request JAK2 exon 12 testing in: a. All patients b. JAK2 V617F negative patients c. I do not have access to JAK2 exon 12 testing in my institution
Treatment of PV: 10. Do you offer aspirin to all PV patients with no contraindications to anti-platelets? a. Yes b. Only in patients with cardiovascular risk factors
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
c. Only in patients who have cardiovascular disease (for example: coronary artery disease, cerebral vascular disease or peripheral arterial disease) d. No (please indicate in which circumstances you offer aspirin): ______________________ 11. What hematocrit do you phlebotomize to? a. <45% irrespective of gender b. <45% for men and <42% for women c. 45-50% irrespective of gender d. Other (please specify): __________________________________________________ 12. What indications would you use for cytoreductive therapy (choose all that apply): a. Prior thrombotic event b. Age > 60 d. Refractory phlebotomy e. Leukocytosis (WBC > 25 X10>9) 13. Chose which is your preferred 1st line cytoreductive agent for most of your patients and please explain why: a. Interferon (pegylated or not) b. Hydroxyurea c. Ruxolitinib d. Anagrelide Please explain your choice in 1 or 2 sentences: _________________________________________________ 14. Do you use a formal symptom score in your clinical practice? a. Yes b. No 15. If Yes, please indicate which score you use: a. MPN10 score b. Edmonton Symptom Assessment System (ESAS) c. Both d. Other: ________________________________________________________________ 16. In your patients with PV who develop unprovoked venous thromboembolism, in whom there are no contraindications to anticoagulation, you: a. Offer a defined course of anticoagulation b. Recommend indefinite anticoagulation c. Treat with aspirin alone d. Other (please specify): ___________________________________________________
ACCEPTED MANUSCRIPT
Citations:
6. 7. 8. 9.
10.
11.
12. 13.
14.
15.
RI PT
SC
5.
M AN U
4.
TE D
3.
EP
2.
Sirhan, S., et al., Evolving Therapeutic Options for Polycythemia Vera: Perspectives of the Canadian Myeloproliferative Neoplasms Group. Clin Lymphoma Myeloma Leuk, 2015. 15(12): p. 715-27. W, D., Some speculations on the myeloproliferative syndromes. Blood, 1951. 6: p. 372375. Titmarsh GJ, D.A., McMullin MF, et al., How common are myeloproliferative neoplasms? A systematic review and meta-analysis. . Am J Hematol, 2014. 89: p. 581-587. Mehta J, W.H., iqbal SU, Epidemiology of myeloproliferative neoplasms in the United States. Leuk Lymphoma, 2014. 55: p. 585-600. Rollinson DE, H.N., Smith MT et al., Epidemiology of myeolodysplastic syndromes and chronic myeloproliferative disroers in the United States, 2001-2004, using data from the NAACCR and SEER programs. Blood, 2008. 112: p. 45-52. Swerdlow SH, e., WHO Classification of Tumours of Hematopoietic and Lymphoid TIssues. 4th ed. 2017, Lyon, France: International Agency for Research on Cancer Barbui, T., Thiele J, Carobbio A et al., Discriminating between essential thrombocytosis and masked polycythemia vera. Blood, 2014. 89: p. 588-590. Barbui, T., Thiele J, Carobbio A et al., Masked polycythemia vera diagnosed according to WHO and BCSH classification. Am J Hematol, 2014. 89: p. 199-202. Kander, E.M., et al., Practice Patterns in the Diagnosis andTreatment of Polycythemia Vera in the Post-JAK2 V617F Discovery Era. JNCCN Journal of the National Comprehensive Cancer Network, 2016. 14(10): p. 1238-1245. Hultcrantz M, K.S., Andersson TM, Landgren O, Eloranta S, Derolf AR, Dickman PW, Bjorkholm M Patterns of survival among patients with myeloproliferative neoplasms diagnosed in Sweden from 1973 to 2008: a population-based study. . Journal of Clinical Oncology, 2012. 30(24): p. 2995-3001. Ellis, M.H., et al., Treatment of thromboembolic events coincident with the diagnosis of myeloproliferative neoplasms: a physician survey. Thrombosis research, 2014. 134(2): p. 251-4. Marchioli R, F.G., Landolfi R, et al., Vascular and neoplastic risk in a large cohort of patients with polycythemia vera. J Clin Oncol, 2005(23): p. 2224-32. Tefferi A, R.E., Finazzi G et al., Survival and prognosis among 1545 patients with contemporary olycythemia vera: an international study. Leukemia, 2013. 27: p. 18741881. Stein BL, S.S., Sobol U, Halpern A, Shammo J, Rondelli D, Michaelis L, Odenike O, Rademaker A, Zakarija A, McMahon B, Spivak J, Moliterno AR, Age-related differences in disease characteristics and clinical outcomes in polycythemia vera. Leukemia and Lymphoma, 2013. 54(9): p. 1989–1995. Boddu P, M.L., Verstovsek S, Strati P, Kantarjian H, Cortes J, Estrov Z, Pierce S, Pemmaraju N, Patient characteristics and outcomes in adolescents and young adults with classical Philadelphia chromosome-negative myeloproliferative neoplasms. Ann Hematol, 2018. 97: p. 109-121.
AC C
1.
ACCEPTED MANUSCRIPT
EP
TE D
M AN U
SC
RI PT
Barbui, T., How to manage children and young adults with myeloproliferative neoplasms. Leukemia, 2012. 26: p. 1452-1457.
AC C
16.
ACCEPTED MANUSCRIPT
Respondent characteristics Female Male Missing
42 (50%) 42 (50%) 2
Non-malignant hematology
38 (45%)
Malignant hematology
SC
Type of practice
Practice setting
5-9 Number of PV patients seen annually
10-14 15-74
TE D
<5
M AN U
Medical oncology Other Missing Academic Community Mixed Missing
RI PT
Sex
EP
>75
2 (2%) 12 (14%) 2 64 (77%) 14 (17%) 5 (6%) 3 12 (14%) 10 (12%) 15 (17%) 39 (45%) 4 (5%) 6 (7%)
AC C
Missing
32 (38%)
Table 1. Respondent characteristics
Diagnosis and treatment of PV WHO 2016 PV diagnostic criteria Canadian MPN guidelines and WHO 2016 PV diagnostic criteria Guideline awareness Neither Missing
Would request a bone
At diagnosis, including in JAK2 positive patients In JAK2 V617F negative patients
77 (90%) 34 (42%) 5 (6%) 4 29 (37%)
ACCEPTED MANUSCRIPT Would request a bone Other marrow biopsy Missing
35 (44%) 15 (19%) 5
Would offer aspirin to all PV patients Phlebotomize to a target hematocrit <45% irrespective of gender Prior thrombotic event Indications for cytoreduction Age >60
RI PT
70 (91%)
SC
Hydroxyurea as 1st line cytoreductive agent
M AN U
Would offer indefinite anticoagulation for venous thrombosis in a patient with PV Use a formal symptom score in clinical practice
Table 2. Respondent management practices
AC C
Respondents who were aware of the Canadian MPN guidelines were more likely to phlebotomize patients to a target hematocrit of <45% irrespective of gender
P=0.02
EP
Type of practice was associated with respondents offering aspirin to all PV patients without contraindications to anti-platelet therapy
TE D
Univariate Analysis Respondents who saw more PV patients yearly were more likely to use a formal symptom assessment score such as the MPN10 score or the Edmonton Symptom Assessment Score
Younger practitioners were more likely to use age over 60 as an indication for initiating cytoreductive therapy
P=0.001
P=0.04
Multivariate Analysis P=0.001
Table 3. Univariate and multivariate analysis
53 (69%) 64 (80%) 59 (74%)
86 (100%
65 (85%)
10 (13%)
S2152-2650(18)30239-8
DOI:
10.1016/j.clml.2018.07.297
Reference:
CLML 1185
To appear in:
Clinical Lymphoma, Myeloma and Leukemia
Received Date: 9 April 2018 Revised Date:
21 July 2018
Accepted Date: 27 July 2018
Please cite this article as: Habib LA, Kuo KHM, Panzarella T, Gupta V, Trinkaus M, Management of Polycythemia Vera: A survey of Canadian Physician Practice Patterns, Clinical Lymphoma, Myeloma and Leukemia (2018), doi: 10.1016/j.clml.2018.07.297. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Management of Polycythemia Vera: A survey of Canadian Physician Practice Patterns
RI PT
Laura Anne Habib1 Kevin H.M. Kuo1 Tony Panzarella2 Vikas Gupta2 Martina Trinkaus3 1
SC
Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada Address: 200 Elizabeth St, Toronto, ON M5G 2C4, Canada 2
M AN U
Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Canada Address: 610 University Ave, Toronto, ON M5G 2M9, Canada
3
Division of Hematology/Oncology, St. Michael’s Hospital, University of Toronto, Toronto, Canada Address: 30 Bond St, Toronto, ON M5B 1W8, Canada
AC C
EP
TE D
Corresponding author: Laura Anne Habib Email: [email protected] Address: 705-80 Wellesley street east, Toronto, ON, M4Y1H3, Canada
ACCEPTED MANUSCRIPT
Management of Polycythemia Vera: A survey of Canadian Physician Practice Patterns Habib L., Kuo K., Panzarella T., Gupta V., Trinkaus M. Micro Abstract:
RI PT
The literature is scarce about the clinical uptake of the 2016 World Health Organization (WHO) revised classification criteria for the diagnosis of polycythemia vera (PV). A survey of 86 Canadian practicing hematologists/oncologists revealed that heterogeneity exists in the diagnosis and practice of PV. Greater awareness of the diagnostic criteria and Canadian guidelines translates into recommended work up and management of PV patients.
SC
Abstract:
AC C
EP
TE D
M AN U
Background: The 2016 World Health Organization (WHO) revised classification criteria for the diagnosis of polycythemia vera (PV) allows for an earlier detection of masked PV. The literature is scarce about the clinical uptake of new diagnostic algorithms for PV. In a cohort of Canadian hematologists, we aimed to identify how the revised 2016 World Health Organization (WHO) diagnostic criteria of Polycythemia Vera (PV) are being incorporated into hematology practice, and if the treatment of PV is comparable to the approaches outlined by the Canadian Myeloproliferative Neoplasm (MPN) Group.[1] Methods: A cross-sectional survey of practicing Canadian hematologists/oncologists was distributed to active members of the Canadian Hematology Society (CHS) using an online survey-distributing website. Univariate and multivariate analysis was performed. Results: The survey was completed by 86 respondents in total. Only type of practice was associated with respondents offering aspirin to all PV patients (P=0.0009). Respondents who were aware of the Canadian MPN guidelines were more likely to phlebotomize patients to a target hematocrit of <45% irrespective of gender (P=0.042). Younger practitioners were more likely to use age over 60 as an indication for initiating cytoreductive therapy (P=0.0006). Most (85.3%) respondents would recommend indefinite anticoagulation in patients with PV who developed unprovoked venous thromboembolism. Conclusion: The survey confirmed that heterogeneity of practice in diagnosis and management of PV among Canadian hematologists exists, suggesting that targeted education in specific segments of the PV treatment providers may result in wider adoption of the guidelines and diagnostic criteria. Key words: Polycythemia Vera, myeloproliferative neoplasm, survey, management, diagnostic criteria Original Study: Introduction: PV is a stem cell disorder characterized by overproduction of red blood cells and may also result in thrombocytosis and leukocytosis.[2] It has an incidence rate of 1 case per 100 000 persons and
ACCEPTED MANUSCRIPT
a prevalence of 44-57 per 100 000 persons from recent North American data.[3, 4] The median age at presentation is 61 with a median survival of 18.9 years. [4, 5]
RI PT
The 2016 World Health Organization (WHO) revised classification criteria for the diagnosis of PV allows for an earlier detection of masked PV. [1] Changes in diagnosis include a lower hemoglobin threshold to a hemoglobin of >165 g/L [16.5g/dL] (160 g/L [16g/dL] in women) from >185 g/L (165 g/L in men), and inclusion of a bone marrow biopsy.[6] Patients with mPV may present with lower hemoglobin levels and have an increased risk of thrombosis potentially related to later diagnosis and treatment. [7, 8]
M AN U
SC
The Canadian MPN Group have outlined recommendations for management of PV. [1] These recommendations suggest that aspirin be given to all patients with PV unless contra-indicated and that patients undergo cardiovascular risk reduction. They further recommend strict hematocrit control (target hematocrit < 45% in men and women) and cytoreductive therapy for high risk patients (age of > 60 years old and/or prior thrombosis). A survey of 71 American hematologists prior to the revised 2016 WHO criteria found that despite the discovery of the JAK2 mutations, there remained significant variability in the treatment and diagnosis of PV. [9] No survey to date has been performed among Canadian physicians.
Methods:
TE D
We aimed to evaluate the impact of the revised 2016 WHO criteria for the diagnosis of PV among Canadian hematologists practicing in diverse settings. We also aimed to describe the management and treatment of PV among Canadian hematologists as they compare to the approaches outlined by the Canadian MPN Group [1] with the purpose to identify areas in which guidelines lack or should be reinforced, and areas in which education and research is needed.
AC C
EP
Health Sciences Research Ethics Board of the University of Toronto approval was granted in April 2017 for a cross sectional exploratory survey-based study of Canadian hematologist. Potential participants were captured primarily through membership with the Canadian Hematology Society (CHS) which had 299 active members at the time of survey distribution. Members comprised of physicians practicing in diverse settings. Status as a practicing hematologist was self- reported and consent was implied by participating in the survey. Participation was voluntary and anonymous. The survey comprised of 16 questions that characterized the demographics of our respondents and addressed their practice in diagnosis and management of PV. Survey design was adapted from the 2016 American survey published in the Journal of the National Comprehensive Cancer Network.[9] A pilot survey was performed at the Princess Margaret Hospital Myeloproliferative Neoplasm Rounds prior to distribution. The survey was distributed online in English and French using an online survey-distributing website, SurveyMonkey.com™. A reminder email was sent out two weeks following the original request. Each participant was asked to complete the survey only once. The only data available to investigators were survey responses and basic demographics. Three respondents completed the online French survey and 66 the English version. Paper copies of the survey were also distributed in English at the Leukemia Day
ACCEPTED MANUSCRIPT
conference in Toronto, April 6th, 2017, to members of CHS and 17 respondents returned paper copies of the survey.
RI PT
Descriptive statistics for quantitative data have been derived from all surveys completed by eligible participants. Categorical variables have been reported as percentages and normally distributed variables as means and standard deviations.
SC
Univariate analysis assessing age, sex, type of practice, practice setting and number of PV patients seen per year was performed on each of the diagnostic and management questions in the survey. Fisher’s exact test was used if the explanatory variable was categorical and the Wald chisquare test from a multiple logistic regression was used if the explanatory variable was continuous.
M AN U
Multivariable analysis assessing age, sex, type of practice, practice setting and number of PV patients seen per year was performed in relation to awareness of the WHO 2016 guidelines or the Canadian MPN guidelines. Logistic regression using the penalized maximum likelihood method was used to test the joint significance of explanatory variables on outcome. Penalized likelihood is a general approach to reducing small-sample bias in maximum likelihood estimation. A P value less than 0.05 was considered significant given the numerous outcomes and the large number of tests conducted in this exploratory analysis. All analyses were conducted using SAS version 9.4. Results:
EP
TE D
86 respondents completed the survey in total, (69 online surveys and 17 with paper copies). Table 1 describes the respondents’ characteristics, diagnosis and treatment approach. The mean number of patients seen by respondents annually was 22.6 (SD 23.6) and a median of 15 (range of 0-120). 52.4% were aware of the WHO 2016 PV diagnostic criteria while 41.5% were additionally aware of the Canadian MPN guidelines (6.1% were aware of neither). No variable significantly correlated with awareness of the WHO 2016 diagnostic criteria nor the Canadian MPN guidelines on univariate analysis.
AC C
37% of respondents would request a bone marrow biopsy to confirm the diagnosis of PV in JAK2 positive patients. Type of practice was associated with respondents offering aspirin to all PV patients without contra-indications to anti-platelet therapy (P=0.0009) on univariate analysis, while practice setting or number of PV patients seen per year did not. Respondents who were aware of the Canadian MPN guidelines were more likely to phlebotomize patients to a target hematocrit of <45% irrespective of gender (P=0.042). Younger practitioners were more likely to use age over 60 as an indication for initiating cytoreductive therapy which was independent of other confounders in the multivariable analysis (P=0.0006). All respondents chose hydroxyurea as their preferred first line cytoreductive agent. Most (85.3%) respondents would recommend indefinite anticoagulation in patients with PV who developed unprovoked venous thromboembolism (in whom there were no contraindications to anticoagulation). Respondents who saw more PV patients yearly were more likely to use a formal symptom assessment score
ACCEPTED MANUSCRIPT
such as the MPN10 score or the Edmonton Symptom Assessment System (ESAS) on univariate analysis (P=0.015).
RI PT
While 19% of respondents did not have JAK2 exon 12 testing available at their centers, 75% of respondents would request it for all their patients. Respondents who see more PV patients annually were more likely to request JAK2 exon 12 testing on all their patients which was independent of other confounders on multivariable analysis (P=0.032). Discussion:
SC
This survey confirmed that heterogeneity of practice in diagnosis and management of PV among Canadian hematologists persists despite the revised 2016 WHO diagnostic criteria and the guidelines set forth by the Canadian MPN group.
M AN U
Just over one third of our respondents would request a bone marrow biopsy to confirm the diagnosis of PV despite its addition to the revised 2016 WHO criteria. The Canadian MPN Group guidelines differ from the WHO criteria in that they suggest a diagnosis of PV can be made without a bone marrow biopsy if there is presence of elevated red blood cell volume as per the 2008 WHO criteria. [1]
EP
TE D
Our study is limited by a 29% response rate (86/299) and most respondents identifying their practice setting as academic (77.1%). Data regarding the breakdown of the practice setting of members within the CHS is unavailable for comparison. This contrasts with the survey conducted by Kander et al., 2016, which reported a 7.8% response rate from the MPN Research Foundation Database (N=847). Physicians with greater clinical experience or those working in private clinics had a greater tendency to use JAK2 molecular testing as a preferred diagnostic test. Nearly half of their respondents continued to use a sex-dependent hematocrit goal rather than a target hematocrit of 45% regardless of gender. Physicians in academic practice were more likely to recommend aspirin to their PV patients. Similar to our results, hydroxyurea was the preferred cytoreductive agent among 82% of respondents.[9]
AC C
Data from the national Swedish Cancer Registry including 9384 patients with MPN (PV=4389) followed between 1973-2009 demonstrated moderately reduced (36% lower) life expectancy in patients with PV when compared to the general population.[10] First line cytoreductive agents used in this cohort included hydroxyurea and radioactive phosphorus as per national guidelines at the time. An improvement in survival was observe in PV patients over time. This was attributed to prevention of thromboembolic events following the introduction of aspirin prophylaxis and phlebotomy titrated to target hematocrit. Results of a survey of 73 hematologists in 2014 demonstrated a lack of consensus for the treatment of thromboembolic complications in patients with an MPN.[11] Canadian hematologists appear to be less heterogeneous as 85.3% of our respondents would recommend indefinite anticoagulation for unprovoked venous thromboembolism in patients with PV. Clinical trials are lacking in this area. Older age has been shown to be a risk factor for thrombotic complications, transformation to AML and poorer overall survival in large cohort studies.[12, 13] Physicians in our survey were more likely to initiate cytoreduction in patients over the age of 60. As the age of providers
ACCEPTED MANUSCRIPT
M AN U
SC
RI PT
changes so too might the age at which patients may be recognized to have PV particularly as the revised WHO classification criteria allows for an earlier detection of masked PV. The preferred cytoreductive agent of choice by our respondents was hydroxyurea. Less is known regarding which younger patients warrant cytoreduction and which agent to use. Patients less than 40 years of age constitute 2.2-6.6% of yearly MPN cases in the United States.[5] Our survey did not address the distribution of the age of patients with PV. A retrospective study comparing patients with PV less than 45 years old to those older than 65 years old (n=204 patients; n=120 <45 years old) showed comparable rates of thrombotic complications aside from an increased rate of splanchnic vein thrombosis (13% vs 2%, p=0.0056).[14] Transformation to acute myeloid leukemia or myelofibrosis occurred at similar rates. While complications from PV similarly affect the younger population, thrombotic and transformational events were not predicted by younger age in a recent retrospective MPN cohort study including 37 adolescent and young adult patients (16-39 years old) with PV (total n= 2206).[15] Expert opinion recommends a risk adapted approach in asymptomatic young adult patients with PV offering aspirin prophylaxis with phlebotomy titrated to a hematocrit below 45% in the low risk population.[16] Cytoreductive therapy is recommended to the high-risk group. Hydroxyurea remains the first choice cytoreductive agent in patients who have experienced a life-threatening thrombotic event. While no robust data supports the theory of leukomogenicity of hydroxyurea, interferon-alpha and the pegylated form are considered alternative first line options.[16] Long term anticoagulation is recommended for unprovoked thromboembolism including splanchnic vein thrombosis and Budd-Chiari syndrome.[16]
EP
Clinical Practice Points:
TE D
Our survey results indicate that awareness of the guidelines and the updated diagnostic criteria translated into adopting approaches advocated in these documents. Only 42% of our respondents were aware of the Canadian MPN Group guidelines in addition to the 2016 revised WHO diagnostic criteria. This suggests that targeted education in specific segments of the PV treatment providers in Canada may result in wider adoption of the guidelines and diagnostic criteria.
AC C
The 2016 World Health Organization (WHO) revised classification criteria for the diagnosis of polycythemia vera (PV) allows for an earlier detection of masked PV. The literature is scarce about the clinical uptake of new diagnostic algorithms for PV. A cross-sectional survey of Canadian hematologists/oncologists was distributed to identify how these newly revised WHO criteria are being incorporated into hematology practice and to determine if treatment of PV is comparable to the approaches outlined by the Canadian Myeloproliferative Neoplasm (MPN) Group. 86 respondents completed the survey. Only type of practice was associated with respondents offering aspirin to all PV patients (P=0.0009). Respondents who were aware of the Canadian MPN guidelines were more likely to phlebotomize patients to a target hematocrit of <45% irrespective of gender (P=0.042). Younger practitioners were more likely to use age over 60 as an indication for initiating cytoreductive therapy (P=0.0006). Most (85.3%) respondents would recommend indefinite anticoagulation in patients with PV who developed unprovoked venous thromboembolism. Results revealed that heterogeneity exists in the diagnosis and practice of PV among Canadian hematologists despite the revised 2016 WHO diagnostic criteria and the guidelines set forth by the Canadian MPN group. Greater awareness of guidelines and
ACCEPTED MANUSCRIPT
updated diagnostic criteria translates into recommended work up and management of PV patients. Targeted education of PV criteria may improve adoption of the diagnostic criteria and management guidelines.
AC C
EP
TE D
Table 1. Respondent characteristics
M AN U
SC
RI PT
Appendix:
Table 2. Respondent management practices
AC C
EP
TE D
M AN U
Table 3. Univariate and multivariate analysis
SC
RI PT
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT
Survey Questionnaire: Demographics:
Diagnosis of Polycythemia Vera (PV):
M AN U
SC
RI PT
1. Please indicate your age: __________________________________________________________ 2. Please indicate your gender: a. Female b. Male 3. Your practice is primarily: a. Non-malignant hematology b. Malignant hematology c. Medical oncology d. Other (please specify): ____________________________________________________ 4. Your practice is in which of the following settings: a. Academic b. Community c. Other (please specify): _____________________________________________________ 5. Please indicate on average how many patients with PV do you see in a year: ________________
AC C
EP
TE D
6. Are you aware of the following: a. WHO 2016 PV diagnostic criteria b. Canadian MPN Guidelines c. Both d. Neither (please specify any other guidelines you may be aware of): _______________ 7. If a 65-year-old female with a hemoglobin of 165 g/L (16.5g/dL) is referred to you who is JAK2 V617F positive with a low erythropoeitin level, would you (chose all that apply): a. Consider her to have PV b. Request a bone marrow biopsy to confirm a myeloproliferative disorder c. Ensure other etiologies for an erythrocytosis are ruled out d. Order Calreticulin molecular testing to assist in prognostication of the patient’s myeloproliferative disorder 8. Under what circumstance would you perform a bone marrow biopsy in polycythemia vera? a. All cases at diagnosis including those who are JAK2 positive b. Those who are JAK2 V617F negative c. Other (please specify): _________________________________________________ 9. Do you request JAK2 exon 12 testing in: a. All patients b. JAK2 V617F negative patients c. I do not have access to JAK2 exon 12 testing in my institution
Treatment of PV: 10. Do you offer aspirin to all PV patients with no contraindications to anti-platelets? a. Yes b. Only in patients with cardiovascular risk factors
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
c. Only in patients who have cardiovascular disease (for example: coronary artery disease, cerebral vascular disease or peripheral arterial disease) d. No (please indicate in which circumstances you offer aspirin): ______________________ 11. What hematocrit do you phlebotomize to? a. <45% irrespective of gender b. <45% for men and <42% for women c. 45-50% irrespective of gender d. Other (please specify): __________________________________________________ 12. What indications would you use for cytoreductive therapy (choose all that apply): a. Prior thrombotic event b. Age > 60 d. Refractory phlebotomy e. Leukocytosis (WBC > 25 X10>9) 13. Chose which is your preferred 1st line cytoreductive agent for most of your patients and please explain why: a. Interferon (pegylated or not) b. Hydroxyurea c. Ruxolitinib d. Anagrelide Please explain your choice in 1 or 2 sentences: _________________________________________________ 14. Do you use a formal symptom score in your clinical practice? a. Yes b. No 15. If Yes, please indicate which score you use: a. MPN10 score b. Edmonton Symptom Assessment System (ESAS) c. Both d. Other: ________________________________________________________________ 16. In your patients with PV who develop unprovoked venous thromboembolism, in whom there are no contraindications to anticoagulation, you: a. Offer a defined course of anticoagulation b. Recommend indefinite anticoagulation c. Treat with aspirin alone d. Other (please specify): ___________________________________________________
ACCEPTED MANUSCRIPT
Citations:
6. 7. 8. 9.
10.
11.
12. 13.
14.
15.
RI PT
SC
5.
M AN U
4.
TE D
3.
EP
2.
Sirhan, S., et al., Evolving Therapeutic Options for Polycythemia Vera: Perspectives of the Canadian Myeloproliferative Neoplasms Group. Clin Lymphoma Myeloma Leuk, 2015. 15(12): p. 715-27. W, D., Some speculations on the myeloproliferative syndromes. Blood, 1951. 6: p. 372375. Titmarsh GJ, D.A., McMullin MF, et al., How common are myeloproliferative neoplasms? A systematic review and meta-analysis. . Am J Hematol, 2014. 89: p. 581-587. Mehta J, W.H., iqbal SU, Epidemiology of myeloproliferative neoplasms in the United States. Leuk Lymphoma, 2014. 55: p. 585-600. Rollinson DE, H.N., Smith MT et al., Epidemiology of myeolodysplastic syndromes and chronic myeloproliferative disroers in the United States, 2001-2004, using data from the NAACCR and SEER programs. Blood, 2008. 112: p. 45-52. Swerdlow SH, e., WHO Classification of Tumours of Hematopoietic and Lymphoid TIssues. 4th ed. 2017, Lyon, France: International Agency for Research on Cancer Barbui, T., Thiele J, Carobbio A et al., Discriminating between essential thrombocytosis and masked polycythemia vera. Blood, 2014. 89: p. 588-590. Barbui, T., Thiele J, Carobbio A et al., Masked polycythemia vera diagnosed according to WHO and BCSH classification. Am J Hematol, 2014. 89: p. 199-202. Kander, E.M., et al., Practice Patterns in the Diagnosis andTreatment of Polycythemia Vera in the Post-JAK2 V617F Discovery Era. JNCCN Journal of the National Comprehensive Cancer Network, 2016. 14(10): p. 1238-1245. Hultcrantz M, K.S., Andersson TM, Landgren O, Eloranta S, Derolf AR, Dickman PW, Bjorkholm M Patterns of survival among patients with myeloproliferative neoplasms diagnosed in Sweden from 1973 to 2008: a population-based study. . Journal of Clinical Oncology, 2012. 30(24): p. 2995-3001. Ellis, M.H., et al., Treatment of thromboembolic events coincident with the diagnosis of myeloproliferative neoplasms: a physician survey. Thrombosis research, 2014. 134(2): p. 251-4. Marchioli R, F.G., Landolfi R, et al., Vascular and neoplastic risk in a large cohort of patients with polycythemia vera. J Clin Oncol, 2005(23): p. 2224-32. Tefferi A, R.E., Finazzi G et al., Survival and prognosis among 1545 patients with contemporary olycythemia vera: an international study. Leukemia, 2013. 27: p. 18741881. Stein BL, S.S., Sobol U, Halpern A, Shammo J, Rondelli D, Michaelis L, Odenike O, Rademaker A, Zakarija A, McMahon B, Spivak J, Moliterno AR, Age-related differences in disease characteristics and clinical outcomes in polycythemia vera. Leukemia and Lymphoma, 2013. 54(9): p. 1989–1995. Boddu P, M.L., Verstovsek S, Strati P, Kantarjian H, Cortes J, Estrov Z, Pierce S, Pemmaraju N, Patient characteristics and outcomes in adolescents and young adults with classical Philadelphia chromosome-negative myeloproliferative neoplasms. Ann Hematol, 2018. 97: p. 109-121.
AC C
1.
ACCEPTED MANUSCRIPT
EP
TE D
M AN U
SC
RI PT
Barbui, T., How to manage children and young adults with myeloproliferative neoplasms. Leukemia, 2012. 26: p. 1452-1457.
AC C
16.
ACCEPTED MANUSCRIPT
Respondent characteristics Female Male Missing
42 (50%) 42 (50%) 2
Non-malignant hematology
38 (45%)
Malignant hematology
SC
Type of practice
Practice setting
5-9 Number of PV patients seen annually
10-14 15-74
TE D
<5
M AN U
Medical oncology Other Missing Academic Community Mixed Missing
RI PT
Sex
EP
>75
2 (2%) 12 (14%) 2 64 (77%) 14 (17%) 5 (6%) 3 12 (14%) 10 (12%) 15 (17%) 39 (45%) 4 (5%) 6 (7%)
AC C
Missing
32 (38%)
Table 1. Respondent characteristics
Diagnosis and treatment of PV WHO 2016 PV diagnostic criteria Canadian MPN guidelines and WHO 2016 PV diagnostic criteria Guideline awareness Neither Missing
Would request a bone
At diagnosis, including in JAK2 positive patients In JAK2 V617F negative patients
77 (90%) 34 (42%) 5 (6%) 4 29 (37%)
ACCEPTED MANUSCRIPT Would request a bone Other marrow biopsy Missing
35 (44%) 15 (19%) 5
Would offer aspirin to all PV patients Phlebotomize to a target hematocrit <45% irrespective of gender Prior thrombotic event Indications for cytoreduction Age >60
RI PT
70 (91%)
SC
Hydroxyurea as 1st line cytoreductive agent
M AN U
Would offer indefinite anticoagulation for venous thrombosis in a patient with PV Use a formal symptom score in clinical practice
Table 2. Respondent management practices
AC C
Respondents who were aware of the Canadian MPN guidelines were more likely to phlebotomize patients to a target hematocrit of <45% irrespective of gender
P=0.02
EP
Type of practice was associated with respondents offering aspirin to all PV patients without contraindications to anti-platelet therapy
TE D
Univariate Analysis Respondents who saw more PV patients yearly were more likely to use a formal symptom assessment score such as the MPN10 score or the Edmonton Symptom Assessment Score
Younger practitioners were more likely to use age over 60 as an indication for initiating cytoreductive therapy
P=0.001
P=0.04
Multivariate Analysis P=0.001
Table 3. Univariate and multivariate analysis
53 (69%) 64 (80%) 59 (74%)
86 (100%
65 (85%)
10 (13%)