Myeloproliferative disorder lecture for students

1. MYLOPROLIFERATIVE DISORDERS
Col Dr Asif Niaz

2. WHO CLASSIFICATION OF CMPD
 Ch Myeloid leukemia
 Ch Neutrophillic leukemia
 Ch Eosinophillic leukemia / Hyper Eio
Synd
 Polycythemia Vera
 Essential Thrombocythemia
 Myelofibrosis
 CMPD unclassifiable

3. COMMON FEATURES
 Specific clincopathologic criteria for diagnosis and
distinct
 diseases, have common features
 Increased number of one or more myeloid cells
 Hepatosplenomegaly
 Hypercatabolism
 Clonal marrow hyperplasia without dysplasia
 Predisposition to evolve

4. Bone marrow stem cell
Clonal abnormality
Granulocyte
precursors
Red cell
precursors
Megakaryocytes Reactive
fibrosis
Essential
thrombocytosis
(ET)
Polycythaemia
rubra vera
(PRV)
Myelofibrosis
AML
Chronic
myeloid
leukemia
70%
10% 10%
30%

5. POLYCYTHEMIA
 True / Absolute
 Primary Polycythemia
 Secondary Polycythemia
 Epo dependent
 Hypoxia dependent
 Hypoxia independent
 Epo independent
 Apparent / Relative
 Reduction in plasma volume

6. CAUSES OF SECONDARY POLYCYTHEMIA
 ERYTHROPOIETIN (EPO)-MEDIATED
 Hypoxia-Driven
 Chronic lung disease
 Right-to-left cardiopulmonary vascular shunts
 High-altitude habitat
 Chronic carbon monoxide exposure (e.g., smoking)
 Hypoventilation syndromes including sleep apnea
 Renal artery stenosis or an equivalent renal pathology
 Hypoxia-Independent (Pathologic EPO Production)
 Malignant tumors
 Hepatocellular carcinoma
 Renal cell cancer
 Cerebellar hemangioblastoma
 Nonmalignant conditions
 Uterine leiomyomas
 Renal cysts
 Postrenal transplantation
 Adrenal tumors
 EPO RECEPTOR–MEDIATED
 Activating mutation of the erythropoietin receptor
 DRUG-ASSOCIATED
 EPO Doping
 Treatment with Androgen Preparations

7. Primary Polycythemia

8. CAUSES
 +Mutation
 P vera (JAK 2)
 Chuvash polycythemia (VHL)
 Other gene mutations

9. PATHOPHYSIOLOGY OF POLYCYTHEMIA

10. POLYCYTHEMIA VERA
 P. vera is a rare disease
 Median age 60 - 65 years
 Clinical features
 Attributed to increased blood viscosity and
poor oxygen delivery to organs (brain)
 Poor O2 delivery leads to ischemia and
thrombosis
 Expanded blood volume and viscosity leads to
increased cardiac work load

11. P. VERA - SYMPTOMS & SIGNS
 Symptoms
 Headache
 Weakness
 Pruritis (aquagenic)
 Dizziness
 Diaphoresis
 Visual disturbance
 Weight loss
 Signs
 Splenomegaly 70%
 Skin plethora 67%
 Hepatomegaly40%
 Conjunctival plethora 59%
 Systolic Hypertension 72%

12. CLINICAL FEATURES
 Plethora
 Persistent leukocytosis
 Persistent thrombocytosis
 Microcytosis secondary to iron deficiency
 Splenomegaly
 Generalized pruritus (after bathing)
 Unusual thrombosis (e.g., Budd-Chiari
syndrome)
 Erythromelalgia (acral dysesthesia and
erythema)

13. P. VERA - DIAGNOSIS
 Criteria
 RBC mass elevated
 SaO2 > 92%
 Splenomegaly (or)
 thrombocytosis
 Leukocytosis
 high LAP
 high B12
 Significance
 True vs. spurious
 R/O most 2 causes
 Evidence for MPD
 False Positive 0.5%
 smokers, drinkers

14. P. VERA - BONE MARROW BIOPSY

15. TREATMENT
1. Phlebotomy : goal Hct<42%/45%5
2. Low dose aspirin in all
3. Hydroxyurea if high risk of thrombosis
(Age>60, prior thrombosis)
4. Symptomatic (allopurinol, antihistamines)

16. Age > 70
Hydroxyurea
32P?
Age 50 - 70
Hydroxyurea
Phlebotomy
Age < 50
Phlebotomy
Hydroxyurea
P. Vera
Phlebotomize to HCT < 45
TREATMENT OPTIONS – SUMMARY

17. TREATMENT OPTIONS - PHLEBOTOMY
 Advantages
 quick, easy
 less trips to clinic
 low risk of cancer
 no medication need
 compliance
 Disadvantages
 thrombosis risk
 symptoms of iron
deficiency
 perhaps faster to
“spent phase”
 vascular access
 cardiovascular
effects
 no effect on spleen
 no effect on platelets

18. TREATMENT OPTIONS - HYDROXYUREA
 Advantages
 quick and effective
 thrombosis risk low
 reduces spleen size
 lowers all counts
 leukemia risk low
 few side-effects
 Disadvantages
 close monitoring
 childbearing risk
 compliance (daily
medication)
 GI toxicity (rare)
 leukemia risk (?)

19. TREATMENT OPTIONS - 32P
 Advantages
 quick and effective
 thrombosis risk low
 no medication
 follow-up need
minimal
 compliance easier
 reduces spleen size
 lowers all counts
 few side-effects
 Disadvantages
 risk of leukemia
 uncontrolled effects
 childbearing risk
 radiation issues

20. Complications
Lifetime transformation
 Polycythemia Vera  Myelofibrosis--20%4
 Polycythemia Vera  AML/MDS--- 7%
 Polycythemia Vera  CML-- rare
4 Tefferi A, et al. Long-term survival and blast transformation in molecularly annotated
essential thrombocythemia, polycythemiavera, and myelofibrosis. Blood. 2014
Oct;124(16):2507-13. Epub 2014 Jul 18.

21. QUESTION
1. A 66 year old male is evaluated for a 1-month h/o headache and
blurred vision, early satiety, and itching that occurs after
showering. He has a 90-pack-year smoking history. He has no
history of cardiopulmonary or sleep disorders, no other medical
problems, and he takes no medications.
On exam, temp is nl, BP 160/90, HR 90, RR 18, BMI 35, SaO2
94% on ambient air. His face is erythematous and round.
Cardiopulmonary and neurologic exam are normal. Abdominal
exam +splenomegaly.
Labs:
Hb: 19g/dL
WbC 13,500/uL w/ nl differentiation
Plt 595,000

22. 1. Which of the following is the most
appropriate next step in diagnosis?
A. BCR-ABL gene analysis
B. Bone marrow biopsy
C. Epo level
D. Polysomnography