1. MLAB 1415- Hematology Keri Brophy-Martinez
MYELOPROLIFERATIVE DISORDERS (MPDs)

2. CHRONIC MYELOPROLIFERATIVE DISORDERS (MPDs)
Defect found in pluripotential hematopoietic stem cell due to a genetic mutation
Production of a pathogenic clone
Bone marrow and peripheral blood show increases in RBCs, WBCs and/or platelets
Clonal expansion
Characterized by a hypercellular bone marrow with increased quantities of one or more cellular lineages in the peripheral blood.

3. MPDs Most common diseases included in the WHO classification of MPDs:
Chronic myelogenous leukemia (CML) Ph positive
Polycythemia rubra vera (PRV or PV)
Essential thrombocythemia (ET)
Primary myelofibrosis (PMF)
MPDs present in a clinically stable phase that may transform to an aggressive cellular growth phase

4. General Features of MPDs
Occurs in persons over the age of 50
Peak incidence over age 60
Onset is gradual

5. Clinical Features of MPDs
Hemorrhage
Thrombosis
Infection
Pallor
Weakness
Hepatosplenomegaly, splenomegaly
Night sweats
Weight loss

6. Chronic Myelocytic Leukemia -CML-

7. CML Also known as Chronic Granulocytic Leukemia (CGL)
A clonal myeloproliferative disorder
Observe marked leukocytosis and excessive production of granulocytes at all stages of maturation
Etiology unknown (95% of cases)
Seen more commonly in males
Associated with acquired chromosomal abnormality called Philadelphia Chromosome
90-95% of patients with CML carry Philadelphia Chromosome
Translocation of chromosomes 9 and 22 t(9:22)

8. Philadelphia Chromosome
Main portion of the long arm of chromosome 22 is deleted and translocated to distal end of long arm of chromosome 9, and a small part of chromosome 9 reciprocally translocates to the broken end of chromosome 22

9. Three Phases of CML Unresponsive to treatment
Chronic
Controllable with chemotherapy
Lasts 2-5 years
Accelerated
Lasts 6-18 months
10-19% blasts in PB and BM
Low Platelet counts
Increasing WBC counts
Blast crisis
Involves the PB, BM, extramedullary tissue
Unresponsive to treatment
Prognosis less than 6 months
> 20% blasts in bm

10. Blasts in accelerated phase
CML with left shift
Blasts in blast crisis

11. Laboratory Findings in CML
Extreme leukocytosis (WBC > 100,000 x 109/L)
Marked left shift
Predominance of segs and myelocytes
Thrombocytosis (can exceed 1000 x 109/L)
Variant platelet shapes
Function can be abnormal
Normochromic-normocytic anemia (Hgb 9-13 g/dL)
NRBC’s rare
Bone marrow M:E ratio is 10:1(Hypercellular)
Low LAP score (leukemoid reaction has high LAP)
Uric acid elevated- due to cell turnover

12. Chronic myelogenous leukemia (CML)
Treatment
Chemotherapy to reduce the myeloid mass
Bone marrow/stem cell transplant
Imatinib mesylate to inhibit tyrosine kinase

13. Polycythemia
Erythrocytosis with increased hgb concentration and red cell mass (hct)
Classified into two types
Absolute- Result from increased red cell mass
Polycythemia vera (PV)
Secondary polycythemia
Relative- Due to a decrease in plasma volume

14. Polycythemia Vera (PV)
Stem cell disorder characterized by an increase in red blood cell mass and total blood volume.
Mutation in JAK2 gene- activated erythrocyte production
EPO levels are decreased to normal
Cell death is inhibited
There can also be an increase in myeloid and megakaryocytic elements in the bone marrow.
Peak incidence in white males, around age 60

15. Clinical Features: Polycythemia vera
Patients have a ruddy cyanotic complexion due to congestion of blood vessels. “Plethora”
Itching(pruritus)
Headache
Weakness
Fever and night sweats
Splenomegaly
Brain circulatory disorders
Myocardial infarction

16. Lab Features of PV Absolute erythrocytosis of 6-10 x 10 12/L
Hemoglobin Concentrations
Male: >18.5 g/dL
Female: >16.5 g/dL
Hct Concentrations
Male: 52%
Female: 48%
Increased WBC, plts
Bone marrow
Hypercellular

17. Polycythemia vera Treatment Prognosis
Therapeutic phlebotomy for rapid reduction of RBC mass.
Radioactive phosphorous for myelosuppression.
Prognosis
Survival time from diagnosis is 8-15 years
10-15% of patients convert to acute nonlymphocytic leukemia.

18. Secondary polycythemias
EPO levels increased
Causes of increased secretion of erythropoietin
Increase in erythropoietin in response to tissue hypoxia
High altitude
Chronic pulmonary disease
Obesity/sleep apnea
Smoking
Familial hemoglobin variants
High oxygen affinity hemoglobinopathies
Inappropriate increase in erythropoietin
Renal cysts or renal transplants due to tissue hypoxia of the juxtaglomerular apparatus that generates EPO
Neoplasms
Endocrine disorders

19. Relative polycythemia
Red cell mass normal
Decreased plasma volume
Normal EPO
Mild polycythemia

20. Essential thrombocythemia
Defect in megakaryocytic line
Results in increase in megakaryocytes in the BM
Increase in platelets in PB
Platelet abnormalities in diameter, shape, granularity, function
Synonyms include primary thrombocythemia, idiopathic thrombocytosis, primary thrombocytosis

21. ET Platelet count is > 600 x 109/L Giant Bizarre platelets
Platelet aggregates

22. Primary myelofibrosis
Characteristics
Marrow fibrosis
90% of attempts result in dry tap.
Fibroblasts and increased collagen production lock in the marrow contents.
Extramedullary hematopoiesis occurs in spleen and liver
Splenomegaly, hepatomegaly
Left shift, thrombocytosis with bizarre platelets, teardrops, elliptocytes, ovalocytes

23. Primary myelofibrosis
Treatment
Transfusion for anemia
Iron, folate and B12
Steroids
Splenectomy
BM transplant
Prognosis
Median survival time is about 5 years from time of diagnosis.

24. References
McKenzie, Shirlyn B., and J. Lynne. Williams. "Chapter 21." Introduction. Clinical Laboratory Hematology. Boston: Pearson, Print