chronic myeloproliferative disorder

CHRONIC MYELOPROLIFERATIVE

DISORDER

TYPES1. Chronic Myelogenous Leukemia

2. Polycythemia vera3. Essential Thrombocytosis

4. Primary Myelofibrosis

CHRONIC MYELOGENOUS LEUKEMIA

DESCRIPTIONPrimarily Adults ( 25-60 y/o )

Peak age 4th – 5th

> 90% Philadelphia Chromosome

t(9,22)(q34;q11)ABL-BCR gene translocationAffect Pluripotent stem cell

Net effect is Unregulated cell division & inhibition of apoptosis

PHILADELPHIA CHROMOSOME

Clinical Course Insidious Mild-Moderate Anemia

Microcytic to Macrocytic anemiaHypermetabolic state

Organomegaly Extramedullary Hematopoiesis Hepatosplenomegaly Mild Lymphadenopathy

CLINICAL COURSE Median survival is 3 years 50% enter an Accelerated PhaseIncreasing anemia, thrombocytopenia, striking basophilia

6-12 months later AML - Blastic crisis

50% Blast crisis

PBSMarked LeukocytosisPredominantly pmns, metamyelocytes, myelocytes

Less 10% are MyeloblastEosinophilia & BasophiliaThrombocytosis

DESCRIPTION

DESCRIPTION BM Hypercellular 100%

Composed mostly Maturing Granulocytic precursors

PBS- CML

Extramedullary Hematopoiesis Hepatosplenomegaly Mild Lymphadenopathy

DESCRIPTION

FEATURE LEUKEMOIDREACTION

CHRONIC MYELOGENOUSLEUKEMIA

1. WBC < 50 x 109/L > 50 x 109/L

2. Toxic Granulation

Positive Negative

3. Basophilia Absent Greater basophia

4. Cell Bands-prominent

Immature all stages, particularly myelocyte

5. LAP High > 100 Low < 10

6. Splenomegaly Absent Present

Philadelphia Chromosome

Absent Present

TREATMENT BCR-ABL kinase inhibitors

May not prevent progression to crisis

Allogenic bone marrow transplantMost effective Tx

POLYCYTHEMIA VERA Clonal D/O of pluripotent stem cell

Undetectable levels of eryhtropoietin

Increase in Myeloid Stem cells With progression Lead to

1. myelofibrosis2. Leukemic transformation

POLYCYTHEMIA VERA Late Middle age group blood Viscosity Vascular stasis Thrombotic tendency & Hemorrhagic diasthesis

Gout , Pain on affected organ Death :

30% thrombotic complications – brain, heart

5-10% Bleeding

DIAGNOSIS : All 3 or 2 of Major + 2 Minor MAJOR

Increased Total Erythrocyte Volume- Males > 36ml/Kg- Females > 32ml/Kg

Normal Arterial O2 saturation > 92%Splenomegaly

MINORThrombocytosis > 400 x 10 9/LLeukocytosis > 12 x 10 9 /L Increased NAP Increased Serum Vit B12 > 900 ug/L