MLAB 1415- Hematology Keri Brophy-Martinez

1. MLAB 1415- HematologyKeri Brophy-Martinez Chapter 22: MYELOPROLIFERATIVE DISORDERS (MPD)

2. CHRONIC MYELOPROLIFERATIVE DISORDERS (MPD) • Neoplastic clonal proliferation of hematopoietic precursors • Defect found in pluripotential hematopoietic stem cell • Bone marrow and peripheral blood show increases in RBCs, WBCs and/or platelets • 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) • Idiopathic myelofibrosis • Clinically, patients with MPD present in a clinically stable phase that may transform to an aggressive cellular growth phase such as acute leukemia or just a more aggressive form of MPD

4. General Features of MPD • Affect middle-aged and older adults, peaks in the fifth to seventh decade of life • Onset is gradual

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

6. Lab Findings of MPD • Anemia or polycythemia • Leukoerythroblastosis • Leukocytosis • Thrombocytosis, bizarre platelets • Decreased bone marrow iron

7. Chronic Myelocytic Leukemia

8. CML • Also known as Chronic Granulocytic Leukemia (CGL) • A clonal myeloproliferative disorder of hematopoietic pluripotent cell transformation characterized by marked leukocytosis and excessive production of granulocytes at all stages of maturation • Etiology unknown (95% of cases) • 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)

9. 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

10. Three Phases of CML • 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 • Unresponsive to treatment • Prognosis less than 6 months • > 20% blasts in bm

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 • Bone marrow M:E ratio is 10:1 • Low LAP score (leukemoid reaction has high LAP)

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

13. Chronic myelogenous leukemia (CML) • Treatment • Chemotherapy to reduce the myeloid mass • Bone marrow transplant • Interferon (myelosuppressive drug) • Gleevec (molecular targeted therapy)

14. Polycythemias • Classified into three Groups • Polycythemia vera • Normal or decreased EPO levels • Autonomous cell proliferation • Secondary polycythemia • High altitude • Chronic pulmonary disease • Inappropriate EPO production • Hemoglobins with a high O2 affinity • Relative polycythemia • Dehydration • Stress polycythemia • Pseudopolycythemia

15. Polycythemia Vera • Stem cell disorder characterized by a remarkable increase in red blood cell mass and total blood volume. There is also an increase in myeloid and megakaryocytic elements in the bone marrow. • The clonal neoplastic transformation arises in a pluripotential hematopoietic stem cell • Onset is usually around 60 years of age. • Increased incidence in white males

16. Polycythemia Vera • Causes • Hypersensitivity of erythroid progenitor cells to erythropoietin • Hypersensitivity of erythroid progenitor cells to growth factors other than erythropoietin • Inhibition of cell death, leaves alters cells

17. Polycythemia vera • Clinical features • Patients have a ruddy cyanotic complexion due to congestion of blood vessels. • Itching(pruritus) • Headache • Weakness • Fever and night sweats • Splenomegaly • Brain circulatory disorders • Myocardial infarction

18. 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

19. Polycythemia vera • Treatment • 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.

20. Secondary polycythemias • There are many causes that all result in 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

21. Relative polycythemia • Stress polycythemia • Hypertension • Dehydration causes decreased plasma volume

22. Essential thrombocythemia • Rare chronic MPD in which platelets are increased and function is abnormal. • Synonyms include primary thrombocythemia, idiopathic thrombocytosis, primary thrombocytosis

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

24. Idiopathic myelofibrosis • Characteristics • Marrow fibrosis • 90% of attempts result in dry tap. • Fibroblasts and increased collagen production lock in the marrow contents. • Extramedullary hematopoiesis or myeloid metaplasia of spleen and liver • NRBC’s and immature WBC’s in the peripheral blood, teardrop red cells, abnormal platelets

25. Idiopathic 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.

26. References • McKenzie, Shirlyn B., and J. Lynne. Williams. "Chapter 21." Introduction. Clinical Laboratory Hematology. Boston: Pearson, 2010. Print