Patho - 4th Assessment - Cmpds - 29 Jan 2007

Chronic Myeloproliferative Disorders (CMPDs)

CMPDs AGENDA Definition Pathogenesis Epidemiology Clinical Features Classification

CMPDs Definition - Clonal hematopoeitic stem cell disorders. - Proliferation of one or more of the myeloid lineage. - Effective normal maturation increased numbers of granulocytes, RBCs and/or platelets.

CMPDs AGENDA  Definition  Pathogenesis  Epidemiology  Clinical Features  Classification

CMPDs Pathogenesis - Genetic abnormality occurs in hematopoietic stem cells. - No specific genetic abnormalities have been identified in most CMPDs. - Abnormal activation of tyrosine kinase signal transduction pathways. - Increased transcription of genes that block apoptosis

CMPDs AGENDA  Definition  Pathogenesis  Epidemiology  Clinical Features  Classification

CMPDs Epidemiology - Disease of adult (5th-7th decade). - 6-9/100,000 population annually. - Asia < Europe and America.

CMPDs AGENDA  Definition  Pathogenesis  Epidemiology  Clinical Features  Classification

CMPDs Clinical Features • Insidious clinical onset • Splenomegaly and/or hepatomegaly due to: - sequestration - extramedullary hematopoiesis - leukemic infiltration

- combination • Potential to progress to bone marrow failure due to myelofibrosis or transformation to acute leukemia. • Overlap is frequent

CMPDs AGENDA  Definition  Pathogenesis  Epidemiology  Clinical Features  Classification

CMPDs Classification • Based on: - Lineage of predominant proliferating cells - Prominence o bone marrow fibrosis - Clinical features - Laboratory features including: - PBS examination - BM examination - Cytogenetics - Molecular technique data.

CMPDs  Classification (cont’d) • • • •

CML Polycythemia Vera (PV) Chronic Idiopathic Myelofibrosis (CIMF) Essential Thrombocythemia (ET)

CMPDs • Polycythemia Vera (PV)  Definition - Increased RBC production (autonomous). - +/- excessive myeloid and megakaryocytic proliferation .

 Clinical Features - Related to increased RBC mass - Venous or arterial thrombosis - Headache, dizziness or visual disturbances. - Pruritis - Physical Examination: plethora, +/-splenomegaly, +/- hepatomegaly

CMPDs • PV (cont’d)  Diagnosis - WHO criteria - CBC :

elevated Hgb, Hct +/-Neutrophils +/- basophils +/- thrombocytosis - Morphology: PBS examination

BM examination

CMPDs •

PV (cont’d) 

Complications - Myelofibrosis - Transformation into acute leukemia (~ 510%)

CMPDs • CIMF Definition - Proliferation of mainly megakaryocytic and myeloid elements in the bone marrow with reactive bone marrow fibrosis and extramedullary hematopoiesis. Clinical Features - 30% are asymptomatic (incidental findings). - Fatigue, weight loss, night sweats, fever,

CMPDs • CIMF (cont’d) Diagnosis CBC: - variable (Prefibrotic or Fibrotic stage) - +/- anemia - +/- leukocytosis, Leukopenia or normal WBCs - +/- thrombocytosis, thrombocytopenia, normal

Morphology: - PBS examination: Leukoerythroblastic picture Tear drop RBCs & poikilocytosis

CMPDs •

CIMF (cont’d) 

Complications - Bone marrow failure. - Acute leukemia (5-30 %).

CMPDs •

ET 

Definition - Proliferation of megakaryocytic lineage in the BM. - Sustained thrombocytosis in the blood.



Clinical Features - Asymptomatic (50%) - Vascular occlusions (arteries or veins)

- Bleeding (platelet dysfunction) - +/- Hepatosplenomegaly

CMPDs •

ET (cont’d) Diagnosis WHO criteria: - sustained thrombocytosis >600 x

109/L - Megakaryocytic hyperplasia in BM - Exclusion of other CMPDs - Exclusion of secondary causes

CBC: - Thrombocytosis Morphology : - PBS examination - BM examination (Megakaryocytic hyperplasia)

CMPDs • ET (cont’d) Complications - Myelofibrosis. - Transformation into acute leukemia (~ 5%).

CMPDs OVERLAP in Clinical & Laboratory Features

CMPD (NOS)