Good Samaritan Medical Center, West Palm Beach, FLGood Samaritan Medical Center, West Palm Beach, FL

Guest SpeakerMichael Savona, MDAssociate Professor of MedicineDirector, Hematology Early Therapeutics ProgramVanderbilt-Ingram Cancer Center, Nashville, TN

Vardiman JW. Blood. 2009;114(5):937-51.

PREVALENCE OF MPNs PER 100,000 INDIVIDUALS

Mehta J. Leuk Lymphoma. 2014;55(3):595-600

Primary MF + Post PV MF + Post ET MF PV ET

2013 Sep;27(9):1874-81

WHAT DOES A PV PATIENT LOOK LIKE?PRESENTING SIGNS AND SYMPTOMS

Geyer H. Hematology Am Soc Hematol Educ Program. 2014;2014(1):277-286.

2013 Sep;27(9):1874-81

Tefferi A. Leukemia. 2013;27(9):1874-81.

WHAT DOES A PV PATIENT LOOK LIKE?CLINICAL FINDINGS

2013 Sep;27(9):1874-81

OVERALL SURVIVAL AFTER DIAGNOSIS

Tefferi A. Leukemia. 2013;27(9):1874-81.

Median Survival = 18.9 years

ObservedExpected

100

0

80

60

40

20

P= 0.104

0 20105 15

Years

Number at Risk

1545 84491973 229

PART 1:ESTABLISHING A

DIAGNOSIS

OUR PATIENT: CALVIN

• 59-year-old with left hand clumsiness and difficulty speaking

• Review of symptoms notable for fatigue• Family notes recent reddish complexion• Medical history: diet-controlled

hypercholesterolemia • No medications or drug allergies• No hematological problems in the family• Non-smoker, casual ETOH

CASE PRESENTATION: EXAM AND INITIAL DATA

• BP 176/91; oxygen saturation 95%• Plethoric, ruddy appearance• Regular heart rate and rhythm (S1S2, no M/R/G)• Palpable spleen tip• Neurological examination nonfocal

FURTHER WORKUP

• Complete blood count:– WBC 14.9 x 109/L– Hgb 18.8 g/dl– Platelets 485 x 109/L

• JAK2 V617F mutated

• Epo level: 1.9 mU/mL

QUESTION

A. Oxygen saturation: 95%

B. Platelet count: 485 x 109 L

C. Epo level: 1.9 mU/mL

D. WBC: 14.9 x 109/L

A. B. C. D.

25% 25%25%25%

Which of Calvin’s characteristics are included within the WHO’s criteria for diagnosis of PV?

HISTORICAL PERSPECTIVE

• 1892: Vaquez disease

• 40-year-old with “cyanosis,” vertigo, dizziness, palpitations, and erythrocytosis; post-mortem exam showed marked hepatosplenomegaly

• 1903: A new clinical entity

• Osler publishes case series: “Chronic cyanosis, polycythemia and an enlarged spleen”

Osler W. Br Med J. 1904;1(2246):121-122.

DIFFERENTIAL DIAGNOSIS: EXCLUDE OTHER CAUSES OF “POLYCYTHEMIA”

• Congenital– EPO-receptor

mutation• Acquired

– Polycythemia vera

Primary Polycythemia Secondary Polycythemia

• Congenital– VHL mutation, high affinity

Hb, methemoglobinemia• Acquired

– Hypoxia– Inappropriate EPO production

• *Tumors• “Relative”

– Dehydration, diuretic use, etc.

*Tumors include cerebellar hemangioblastoma, uterine leiomyoma, pheochromocytoma, renal cell carcinoma, hepatocellular cancer, meningioma, parathyroid adenoma

WILLIAM DAMESHEK, 1951: SPECULATIONS ON THE MYELOPROLIFERATIVE SYNDROMES

• Recognizes overlapping features shared by PV and the other “MPD”• Leukocytosis

• Thrombocytosis

• Splenomegaly

• Marrow Fibrosis

Dameshek W. Blood. 1951;6(4):372-5.

“…Manifestations of proliferative activity of the bone marrow cells, perhaps due to a hitherto

undiscovered stimulus”

DAMESHEK’S “MYELOSTIMULATORY” FACTOR

Stein B. JAMA. 2010;303(24):2513-8.

Wild-type JAK2 JAK2 mutated PVJAK2 V617F mutations present in ~95% of PV cases

JAK2 Exon 12 mutations present in ~2-3% of PV cases

*Typically isolated erythrocytosisSimilar rate of MF, AML, thrombosis

*Passamonti F. Blood. 2011; 117(10):2813-6.

WHO CRITERIA 2008: POLYCYTHEMIA VERA

MajorAbsolute erythrocytosis (>18.5 g/dL in men;

>16.5 g/dL in women)JAK2 V617F mutation or similar (JAK2 exon 12)

MinorSubnormal EPO level (<4 mU/mL)Bone marrow trilineage proliferationEndogenous erythroid colony growth

Thiele J. Curr Hematol Malig Rep. 2009;4(1):33-40.

*2 major and 1 minor, or 1 major and 2 minor required for diagnosis

“*AN ALTERNATIVE PROPOSAL”

• Hemoglobin/hematocrit is not a perfect surrogate for increase in red cell mass• WHO criteria identified absolute erythrocytosis in only 35%

and 63% of male and female PV patients

• Prospective, 5-year study showed 28/30 diagnosed with PV, based on ↑RCM, JAK2, and ≥1 minor criteria, but 8 (27%) and 18 (60%) did not meet Hct or Hgb criteria

• Red cell mass and plasma volume studies upgrade ~46% of JAK2-positive ET patients to PV

• Epo levels are neither sensitive nor specific, as they can be normal in PV and suppressed in ET

• EECF is neither widely available nor standardized for use

*Spivak JL. Blood. 2008;112(2):231-9; Johansson PL. Br J Haematol. 2005;129(5):701-5; Silver J. Blood. 2013;122(11):1881-6; Alvarez-Larran A. Haematologica. 2012;97(11):1704-7; Cassinat B. Leukemia. 2008;22(2):452-3..

“MASKED” PV (mPV)

One of Osler’s patients,

Oxford 1916

397 patients with PV marrow morphology

•“Masked” (n=140) vs. overt PV (n=257)• mPV typically male, with history of

arterial thrombosis, and ↑platelets• Similar vascular risk, but ↑rate of

MF/AML, and ↓survival vs. overt PV

•mPV distinguished from ET by Hgb >16/16.5, and Hct 48/49% in M/F

•Plasma volume increase can mask PV, typically in cases of abdominal venous thrombosis with splenomegaly*Masked PV=Hgb values below WHO threshold

Lamy T. Am J Med. 1997; 102(1):14-20; Spivak J. N Eng J Med. 2006; 355(7):737; Barbui T. Am J Hematol. 2014;89(1):52-4.

PROPOSED REVISIONS TO THE DIAGNOSTIC CRITERIA

Tefferi A. Leukemia. 2014;28(7):1407-13.

• Major criteria:Hgb >16.5 g/dl (Hct >49%) in men; >16 g/dl (>48%) in

women

BM trilineage myeloproliferation with pleomorphic megakaryocytes

Presence of JAK2 mutation

• Minor criteria:Subnormal Epo level

Diagnosis would require all 3 major criteria or 2 major and 1 minor criteria

KEY TAKEAWAYS

• WHO criteria work well for many PV patients, but the Hgb threshold may be inadequate for some

• Be mindful of “masked” disease– JAK2 + ET, but generous Hct

– JAK2 + with abdominal venous thrombosis

– Pancytosis and/or splenomegaly but Hgb below threshold

– Bone marrow morphology and RCM testing may better recognize PV in these settings

• Epo level imperfect, EEC testing not routinely available

• Updates have been proposed to WHO diagnostic criteria

PART 2:FRONTLINE

TREATMENT OF PV

CASE REVIEW: CALVIN

• 59-year-old presents to the ER with clumsiness of the left hand and transient difficulties with his speech

• Fatigue is noted, along with ruddy complexion

• BP: 176/91; oxygen saturation 95%

• WBC: 14.9 x 109/L

• Hgb: 18.8 g/dl

• Platelets: 485 x 109/L

• JAK2 V617F positive

• Epo level: 1.9 mU/mL

QUESTIONQUESTION

A. Phlebotomy (P) alone

B. P + Aspirin (A) alone

C. P + A + hydroxyurea

D. P + A + ruxolitinib

E. P + A + interferon alfa

A. B. C. D. E.

20% 20% 20%20%20%

Which of the following would not be considered an appropriate first-line regimen for Calvin?

TREATMENT GOALS TREATMENT GOALS FOR NEWLY-DIAGNOSED PVFOR NEWLY-DIAGNOSED PV

• Reduce cardiovascular complications • Improve disease-related symptoms• Prevent transformation to myelofibrosis (15-

20%) and/or leukemia (3-5%)• Improve overall survival (median 14 years)• ?? Reduce/eliminate JAK2 allele burden• ?? Reduce/eliminate other clones (eg, TET2)

STANDARD FIRST-LINE STANDARD FIRST-LINE TREATMENT TREATMENT FOR NEWLY-DIAGNOSED PVFOR NEWLY-DIAGNOSED PV

• Phlebotomy

• Aspirin

• Hydroxyurea

• Interferon?

• Lifestyle modifications– Counseling about risk of thrombosis and hemorrhage

– Smoking cessation, weight control, exercise

– Management of HTN/DM/HL in susceptible patients

– Avoidance of oral contraceptives

– DVT prophylaxis (exercises, activity, enoxaparin sodium for long flights [controversial] or sedentary periods)

LOW-DOSE ASPIRIN IN PV: ECLAP STUDYLOW-DOSE ASPIRIN IN PV: ECLAP STUDY

• Hypothesis: There is increased synthesis of platelet thromboxane in PV that can be suppressed by aspirin 100 mg daily

• 528 patients: 253 aspirin 100 mg daily, 265 placebo• Inclusion Criteria:

o No clear indication for, or contraindication to, aspirino No significant comorbidities

• Primary endpoints:o Cumulative rates of nonfatal MI, stroke, or death from CV

disease +/- PE or major venous thrombosis

Landolfi R. N Engl J Med. 2004;350(2):114-124.

ECLAP RESULTSECLAP RESULTS

Probability of survival free of MI, stroke, death from CV disease, PE, or DVT

Landolfi R. N Engl J Med. 2004;350(2):114-124.

RR 0.40; [0.18,0.91]; P=0.03Note: there were more smokers in the placebo group; HCT median was 46 during follow-up, with 25% of pts with HCT >48

CONCLUSIONS FROM ECLAPCONCLUSIONS FROM ECLAP

• Aspirin significantly reduced primary endpoint by 60% – Significant decrease in combined endpoint of nonfatal MI,

nonfatal stroke, PE, deep venous thrombosis, or death from any cause

– Significant decrease in rates of thrombosis– No significant difference in rates of major adverse events– No significant reduction in overall and cardiovascular

mortality – No significant increase in major bleeding events

Landolfi R. N Engl J Med. 2004;350(2):114-124.

CARDIOVASCULAR EVENTS AND CARDIOVASCULAR EVENTS AND INTENSITY OF PV TREATMENTINTENSITY OF PV TREATMENT

• Cytoreductive Therapy in Polycythemia Vera– (CYTO-PV) study

• 365 adults w/JAK2+ PV, all treated with:– Low-dose aspirin– Phlebotomy (250-500 cc QOD until target HCT) and/or– Hydroxyurea (0.5-1 g daily until plt <400K)

• Hydroxyurea (HU) recommended for:– Patients at high risk for thrombosis (age >65 years,

previous thrombosis) or – Progressive thrombocytosis or splenomegaly

Marchioli R. N Engl J Med. 2013;368(1):22-33.

CYTO-PV STUDY TARGETSCYTO-PV STUDY TARGETS

• Two study armsoMore intensive Tx (target hct = <45%)o Less intensive Tx (target hct = 45 to 50%)

• Primary end point: Time until death from CV complications or major thrombotic events

• Planned target was 1,000 patients, but slow enrollment and competing trials prevented completion

Marchioli R. N Engl J Med. 2013;368(1):22-33.

CV EVENTS AND INTENSITY OF TREATMENTCV EVENTS AND INTENSITY OF TREATMENT

Marchioli R. N Engl J Med. 2013;368(1):22-33.

1.1 per 100 person-years in the low-hematocrit group 4.4 per 100 person-years

in the high-hematocrit group

WHAT ABOUT INTERFERON (IFN) WHAT ABOUT INTERFERON (IFN) IN NEWLY-DIAGNOSED PV?IN NEWLY-DIAGNOSED PV?

• IFN controls counts and can produce hematologic remission

• Progressively decreases JAK2 mutated clones and can induce molecular remission

• No evidence of leukemogenicity• Pegylated formulation generally well-tolerated,

but still associated with important side effects (flu-like symptoms, depression, autoimmune manifestations, ocular toxicity, etc.)

Kiladjian JJ. Leukemia. 2008;22(11):1990-8; Kiladjian JJ. Blood. 2008;112(8):3065-72.

TREATMENT OF PV WITH PIPOBROMANTREATMENT OF PV WITH PIPOBROMAN

Kiladjian JJ. J Clin Oncol. 2011;29(29):3907-13.

• Kiladjian et al (2011)• 285 patients (all <65 years old)• Two study arms:

oHU 25 mg/kg/d, followed by maintenance (10-15 mg/kg/d)

o Pipobroman 1.25 mg/kg/d, followed by maintenance (0.4-0.7 mg/kg/d)

OVERALL SURVIVAL DATAOVERALL SURVIVAL DATA

Kiladjian JJ. J Clin Oncol. 2011;29(29):3907-13.

TREATMENT-RELATED RISK FACTORS FOR TREATMENT-RELATED RISK FACTORS FOR TRANSFORMATION TO AML AND MDSTRANSFORMATION TO AML AND MDS

Bjorkholm M. J Clin Oncol. 2011;29(17):2410-5.

Treatment Odds Ratio 95% CI

None 1.0 Reference

Radioactive phosphorus (P32) 1.5 0.8 to 2.8

Alkylating agent only 0.9 0.4 to 2.1

HU only 1.2 0.6 to 2.4

Mixed treatment (2 or 3) 2.9 1.4 to 5.9

RISK OF TRANSFORMATION TO AML/MDSRISK OF TRANSFORMATION TO AML/MDSRELATIVE TO CUMULATIVE DOSERELATIVE TO CUMULATIVE DOSE

Bjorkholm M. J Clin Oncol. 2011;29(17):2410-5.

Treatment Odds Ratio 95% CI

HU, g1-499500-999≥1,000

1.51.41.3

0.6 to 2.40.6 to 3.40.5 to 3.3

Radioactive phosphorus (P32), MBq1-499500-999≥1,000

1.51.14.6

0.6 to 3.30.5 to 2.22.1 to 9.,8

Alkylating agents, g1-499500-999≥1,000

1.11.73.4

0.5 to 2.30.6 to 5.0

1.1 to 10.6

KEY TAKEAWAYS

• Aspirin, phlebotomy and hydroxyurea remain the mainstays of therapy for PV

• Reduction of HCT to at least <45% is associated with significant clinical benefit

• Hydroxyurea is not associated with a significant independent risk for leukemia, but the issue is still of concern with long-term use and/or higher doses

• Pegylated interferon can also be considered for newly diagnosed PV

• The role of ruxolitinib in newly diagnosed PV is under investigation

PART 3:INADEQUATE RESPONSE TO HYDROXYUREA

OUR PATIENT: JOSEPH

• 71-year-old diagnosed with PV 3 years ago on the basis of erythrocytosis, thrombocytosis, and JAK2-V617F mutation in the setting of an unprovoked deep vein thrombosis

• Managed successful for 3 years with low-dose aspirin, phlebotomy (goal HCT≤45%), and hydroxyurea (500 g twice daily)

• Presents today with a non healing leg ulcer, fatigue, pruritus, and occasional night sweats

• Patient still requires occasional phlebotomy

HISTORY

• Past medical history– Squamous Cell Carcinoma (SCC)

– Multiple actinic keratosis

• Surgical history– Mohs for SCC (2013)– Right inguinal hernia repair

(2010)

• Medications– Aspirin 81 mg/day– Hydroxyurea 500 mg 2x/day– Atorvastatin 20 mg/day

• Social history– Former Smoker (quit

2008)– Retired attorney– Divorced 1986– Remarried 2001

• Family history– Mother had essential

thrombocythemia– Father with myocardial

infarction at age 68

PHYSICAL EXAM

• HEENT: Within normal limits

• CV/Lungs: Within normal limits

• Spleen: 3 cm below left costal margin

• Skin: Scar on forehead from Mohs surgery, numerous actinic keratoses

LABS

• Complete Blood Count– Hemoglobin: 16.7 g/dL– Hematocrit: 51%– Leukocytes: 16.4 x 109/L– Platelets: 640 x 109/L

• Peripheral smear– Leukocytosis, thrombocytosis, no nucleated red

blood cells, no blasts

• Ferritin decreased, TIBC increased• Chemistries: Within normal limits

QUESTION

A. Complete response

B. Partial remission

C. Intolerant of hydroxyurea

D. Resistant to hydroxyurea

E. Evidence of progression to post-PV MF

A. B. C. D. E.

20% 20% 20%20%20%

What would be the most accurate description of Joseph’s clinical status with respect to PV?

CompleteRemissionCompleteRemission

PartialRemission

PartialRemission Molecular ResponseMolecular Response

• Resolution of PV signs• ≥10 pt. MPN TSS • Near normal counts• No progressive disease

or vascular event• Bone marrow remission

& ≤Gr 1 reticulin fibrosis

• Resolution of PV signs• ≥10 pt. MPN TSS • Near normal counts• No progressive disease

or vascular event• Bone marrow remission

& ≤Gr 1 reticulin fibrosis

• Resolution of PV signs• ≥10 pt. MPN TSS • Near normal counts• No progressive disease

or vascular event

• Resolution of PV signs• ≥10 pt. MPN TSS • Near normal counts• No progressive disease

or vascular event

Peripheral blood granulocytes

•CR – Eradicated mutation•PR - ≥50% allele burden, ≥20% allele burden at baseline

Peripheral blood granulocytes

•CR – Eradicated mutation•PR - ≥50% allele burden, ≥20% allele burden at baseline

Barosi G. Blood. 2013:121(23):4778-4781.

RESPONSE CRITERIA FOR PV (≥12 WEEKS)

Progressive Disease = Post- PV MF, MDS, or AMLProgressive Disease = Post- PV MF, MDS, or AML

Assessing MPN BurdenWHO Diagnosis Does Not Tell Whole Story

MPN Symptoms•MF>PV>ET•Multifactorial•Some ET/PV > MF•Cytoreductive rx frequently not effective

MPN Symptoms•MF>PV>ET•Multifactorial•Some ET/PV > MF•Cytoreductive rx frequently not effective

Cytopenias•MF> ET/PV•Anemia

• MF 75%• TX Dep 25%

•TPN 30%

Cytopenias•MF> ET/PV•Anemia

• MF 75%• TX Dep 25%

•TPN 30%Baseline HealthAGE/ MedicinesComorbidities

Baseline HealthAGE/ MedicinesComorbidities

PRIMARY COMMERCIALLY AVAILABLE MPN DRUGS

ETET

PVPV

MFMF

HydroxyureaHydroxyurea Interferon/Peg-INF

Interferon/Peg-INF AnagrelideAnagrelide RuxolitinibRuxolitinib

++++++ ++++

++++++++ ++ ++

++

++++ ++++ ++++++

++++

++

EXPERIMENTAL – OFF LABEL

Ruxolitinib Approved in PV December 4, 2014

“In patients having inadequate response to or intolerant of

hydroxyurea”

Ruxolitinib Approved in PV December 4, 2014

“In patients having inadequate response to or intolerant of

hydroxyurea”

+ to +++ Strength of Evidence

WHAT DOES INTOLERANCE/RESISTANCE TO HYDROXYUREA IN PV MEAN?

1. Need for phlebotomy (HCT<45%)

2. PLT >400 x 109/L and WBC >10 x 109/L

3. Failure to reduce spleen by > 50%

4. No reduction of spleen symptoms

1. Cytopenias (any)– ANC <1.0 x 109/L– Hemoglobin <100 g/l– Platelets <100 x 109/L

2. Leg ulcers3. GI toxicity4. Fever5. Mucocutaneous manifestations6. Skin cancers

RE

SIS

TA

NC

EIN

TO

LER

AN

CE

Please Note

1.After > 3 Months2.At maximum tolerated dose or 2 g/day

Please Note

1.After > 3 Months2.At maximum tolerated dose or 2 g/day

Please Note

At lowest dose to achieve either a

PR or CR

Please Note

At lowest dose to achieve either a

PR or CR

Barosi G et. al. Br J Haematol. 2009;148:961-3.

CASE CONTINUATION

• Joseph undergoes a repeat bone marrow aspirate and biopsy.

• Results:– 1+ out of 3+ fibrosis, normal cytogenetics.

– Diagnosis:– PV patient intolerant to hydroxyurea

• Ruxolitinib 10 mg twice daily is initiated

QUESTION

A. Control of hematocrit

B. Reduction in splenomegaly, if present

C. Reduction in pruritus

D. Prevention of vascular events

E. All of the aboveA. B. C. D. E.

20% 20% 20%20%20%

Which of the following is among the goals of ruxolitinib therapy in PV?

SIX WEEKS LATER

• Joseph reports marked decrease in fatigue, pruritus, and night sweats

• Spleen no longer palpable• Leg ulcer is healing• Hemoglobin 14.0 g/dL (without phlebotomy),

leukocytes 11 x 109/L, and platelets 390 x 109/L

RUXOLITINIB (SINGLE AGENT) IN PV

BAT

Week 32(Primary analysis)

Week 80

n = 110

n = 112

Crossover to ruxolitinib

•Resistance to or intolerance of HU (modified ELN criteria)

•Phlebotomy requirement

•Splenomegaly

Pre-randomization (Day -28 to Day -1)

Hct 40%-45%

Ra

nd

om

ize

d (

1:1

)

ExtendedTreatment

PhaseRuxolitinib 10 mg BID

Week 208

Week 208

Compared to BAT, results showed that ruxolitinib led to:1.Superior control of hematocrit2.Superior reduction in splenomegaly3.Superior reduction in PV-related symptoms4.Trend for less thrombotic events

Compared to BAT, results showed that ruxolitinib led to:1.Superior control of hematocrit2.Superior reduction in splenomegaly3.Superior reduction in PV-related symptoms4.Trend for less thrombotic events

Vannucchi et al. EHA 2014. Abstract LB-2436.

RESPONSE TRIAL: CHANGE IN PV SYMPTOMS

Median Percentage Changes From Baseline at Week 32 in Individual MPN-SAF Symptom Scores

Improvem

ent

−120

−100

−80

−60

−40

−20

0

20

40

Mesa R. ASH 2014. Abstract 709.

TOXICITY PROFILES OF PV AGENTSTOXICITY PROFILES OF PV AGENTS

Drug Common Adverse Effects

Hydroxyurea • Stomatitis• Leg ulcers• Dry skin, acne

• Gastric pain, diarrhea

Interferon alfa • Neutropenia• Elevated LFTs

• Fatigue• Headache

Ruxolitinib • Headache• Abdominal Pain• Diarrhea

• Fatigue• Dyspnea

Najean Y. Blood. 1997;90(9):3370-7; Kiladjian JJ. Blood. 2008;112(8):3065-72; Mesa R. ASH 2014. Abstract 709.

Kiladjian JJ

POSSIBLE ALGORITHM OF THERAPY OF PV IN 2015

Diagnosis of PV

Front Line CytoreductionHU, or HU vs. INF Clinical Trial

Consider ruxolitinib, INF (if not previously received), or JAK2 clinical trial

Assess Symptom Quartile

by MPN 10Q1:TSS <8Q2:TSS 8-17 Q3:TSS 18-31Q4:TSS ≥32 Decide on need for concurrent cytoreduction

based on risk and symptoms

YES

Monitor for symptom burden, vascular events, progression

Worsening symptom burdenVascular event, progressionPhlebotomy intolerance

Worsening symptom burdenVascular event, progressionHU Resistance/ Intolerance

Assess MPN Risk Score & Symptoms Control Hematocrit (<45%)

Low-dose aspirin in appropriate patients

NO

KEY CASE TAKEAWAYS

• Polycythemia vera is a heterogeneous disease • A subset of patients have worsening symptoms,

splenomegaly, and difficulty with hematocrit control

• Hydroxyurea is largely considered front-line cytoreductive therapy for high-risk PV patients, but some patients have an inadequate response based either on resistance or intolerance

• Ruxolitinib is FDA-approved for patients with PV who have an inadequate response or are intolerant of hydroxyurea

ACTIVITY POST-TEST

QUESTION

A. Oxygen saturation >95%

B. Platelet count: 485 x 109 L

C. Epo level: 1.9 mU/mL

D. WBC: 14.9 x 109/L

A. B. C. D.

25% 25%25%25%

According to the WHO, which of the following would be included among the characteristics that qualify a patient for diagnosis of PV?

QUESTIONQUESTION

A. Phlebotomy (P) alone

B. P + Aspirin (A) alone

C. P + A + hydroxyurea

D. P + A + ruxolitinib

E. P + A + interferon alfa

A. B. C. D. E.

20% 20% 20%20%20%

Which of the following would not be considered an appropriate first-line regimen for the treatment of PV?

QUESTION

A. Control of hematocrit

B. Reduction in splenomegaly, if present

C. Reduction in pruritus

D. Prevention of vascular events

E. All of the aboveA. B. C. D. E.

20% 20% 20%20%20%

Which of the following is among the goals of ruxolitinib therapy in PV?