Noon conference talk

1. NOON CONFERENCE
L A U R E N B O N O M O , T Y I N T E R N

2. SIGNS//SYMPTOMS
An analysis of 1545 patients with PV noted the following findings at time of
diagnosis:
• HTN – 46%
• Palpable spleen – 36%
• Pruritus – 36%
• Vasomotor symptoms (e.g. erythromelagia) – 29%
• Arterial thrombosis – 16%
• Venous thrombosis – 7%
• Major hemorrhage – 4%
Other physical findings that suggest PV include:
• Conjunctival injection
• Facial plethora (ruddy cyanosis)
• Hepatomegaly (rare)
• Excoriations of the skin
• Gouty arthritis/tophi

3. DIAGNOSIS: 2016 WHO CRITERIA
Major criteria
• Hgb > 16.5 g/dL in men or 16.0 g/dL in women
OR
Hct > 49% in men or 48% in women
OR
Increased red cell mass (RCM)
• Bone marrow Bx showing hypercellularity for age with trilineage growth
(panmyelosis) including prominent erythroid, granulocytic, and
megakaryocytic proliferation with pleomorphic, mature megakaryocytes
• Presence of JAK2 V617F or JAK2 exon 12 mutation
Minor criterion
• Subnormal serum erythropoietin level
Diagnosis requires all 3 major criteria OR 2 major plus the 1 minor

5. NOTE:
• Important to ensure criteria not applied to secondary causes of elevated
RCM
• Secondary polycythemia is much more common
• Splenomegaly, leukocytosis, and thrombocytosis are found in all
myeloproliferative neoplasms
• Possible to have a different myeloproliferative disease AND secondary
polycythemia (e.g., hypoxia, EPO-secreting tumor)
• Vital because each of these disorders are treated differently

6. QUESTION 1
What is the leading cause of death in PV?
• A) Infection
• B) Leukemic transformation
• C) Major bleeding events
• D) Thromboembolic events

7. QUESTION 1
What is the leading cause of death in PV?
• A) Infection
• B) Leukemic transformation
• C) Major bleeding events
• D) Thromboembolic events
The annual incidence of thrombosis in PV ranges from 1.8% in patients < 40
years of age to 5.1% in those > 70 years of age.
For perspective, the latter is similar to the annual stroke risk of a 75-year-
old with AFib and a prior thromboembolic event (5.3%).

8. PROGNOSIS//TREATMENT
• Median survival of untreated symptomatic PV has been estimated as 18
mo.
• Patients > 60 years old OR with a history of thrombosis are considered
high risk
• Low-risk, treated PV median survival ~28 years
• Therapeutic phlebotomy, ASA 81 mg
• High-risk, treated PV median survival ~11 years
• Add cytoreductive therapy – hydroxyurea is typically agent of choice
• Interferon or busulfan are acceptable second-line agents
• Patients with venous thromboembolic events should be treated with
appropriate dose of anticoagulation (no studies in this population exist to
determine optimal duration of therapy)
• Overall survival of treated patients is inferior to that of an age- and sex-
matched normal population

9. HEMATOLOGIC TRANSFORMATION
• Post-PV myelofibrosis or evolution to AML/MDS is a major cause of
death in PV
• In a large international study, 5.5% of patients with PV developed
AML/MDS within 15 years
• Risk factors include age > 70 years and history of cytotoxic therapy
other than HU
• Prognosis is quite poor without allogeneic HCT

10. Polycythemia Vera (PV) Chronic myeloid leukemia
(CML)
Pathophysiolo
gy
Excessive accumulation of stem cells
within the bone marrow that interfere
with normal cell growth and maturation
Excessive accumulation of clonal
myeloid cells in hematopoietic tissues;
constitutive tyrosine kinase activity
promotes growth and survival in these
calls
Epidemiology Occurs in all ages and populations
75% of patients present after age 50
Slight male predominance
Average age at diagnosis is 50
Symptoms Majority of patients asymptomatic
Symptoms include aquagenic pruritis,
visual changes, erythromelagia
Up to 50% of patients asymptomatic
Symptoms include fatigue, weight loss,
bleeding
Diagnosis BMBx with either positive JAK mutation
or low EPO
BCR-ABL positive by conventional
cytogenetics or FISH/RT-PCR
Treatment Low-risk: Phlebotomy, ASA
High-risk: Add cytoreductive agent (e.g.,
hydroxyurea)
Possible cure with allogeneic HCT
Disease control without cure using
tyrosine kinase inhibitors

11. QUESTION 2
A 63-year-old man is evaluated for a 1-month history of headache, early
satiety, and itching that occurs after showering. He has a 50-pack-year
smoking history. He has no history of cardiopulmonary or sleep
disorders, no other medical problems, and takes no medications.
On exam, T37.5, BP 150/90, HR 80, RR 16, BMI 30, SpO2 96% on RA. His
face is erythematous and round. Abdominal exam is significant for
splenomegaly.
CBC as follows: 13.5 > 19.0 < 595. CMP is WNL.
Which of the following is the most appropriate next step in diagnosis?
• A) JAK2 exon 12 mutation
• B) Bone marrow biopsy and aspirate
• C) UA and serum EPO level
• D) Polysomnography

12. QUESTION 2
A 63-year-old man is evaluated for a 1-month history of headache, early
satiety, and itching that occurs after showering. He has a 50-pack-year
smoking history. He has no history of cardiopulmonary or sleep
disorders, no other medical problems, and takes no medications.
On exam, T37.5, BP 150/90, HR 80, RR 16, BMI 30, SpO2 96% on RA. His
face is erythematous and round. Abdominal exam is significant for
splenomegaly.
CBC as follows: 13.5 > 19.0 < 595. CMP is WNL.
Which of the following is the most appropriate next step in diagnosis?
• A) JAK2 exon 12 mutation
• B) Bone marrow biopsy and aspirate
• C) UA and serum EPO level
• D) Polysomnography

13. REFERENCES
• Tefferi, A., et al. "Survival and prognosis among 1545 patients with
contemporary polycythemia vera: an international study." Leukemia 27.9
(2013): 1874.
• Tefferi, Ayalew, et al. "Long-term survival and blast transformation in
molecularly-annotated essential thrombocythemia, polycythemia vera and
myelofibrosis." Blood (2014): blood-2014.
• Tefferi, Ayalew, and Tiziano Barbui. "Polycythemia vera and essential
thrombocythemia: 2017 update on diagnosis, risk‐stratification, and
management." American journal of hematology 92.1 (2017): 94-108.
• Tam, Constantine S., et al. "The natural history and treatment outcome of
blast phase BCR-ABL− myeloproliferative neoplasms." Blood 112.5 (2008):
1628-1637.
• Barbui, Tiziano, et al. "Diagnostic impact of the 2016 revised WHO criteria for
polycythemia vera." American journal of hematology 92.5 (2017): 417-419.