Myeloproliferative Disorder

1. Myeloproliferative Disorder STEM CELL DISORDERS WHEREBY YOU GET ABNORMAL PROLIFERATION IN ONE OR MORE CELL LINE DERIVED FROM A COMMON STEM CELL

2. THE INDIVIDUAL FEATURE OF THESE DISEASES RESULT FROM A: • DISTURBED HAEMOPOIETIC MICROENVIRONMENT • CLONAL ABNORMALITY • DISTURBANCE IN HAEMOPOIETIC REGULATION.

3. Myeloproliferative Disorder • Polycythaemia Ruba Vera • Myelofibrosis • Primary Thrombocytopenia • Chronic Myeloid Leukaemia • Myeloproliferative Disorder – unclassifiable • Chronic Eosinophilic Leukaemia • Chronic Myeloid Leukaemia

4. CMPD- COMMON FEATURES • Proliferation and differention of one or more stem cell. • Raised W.C.C.. HB, Platelets • Organomegaly • Extramedullary Haematopoiesis • Clinical, Laboratory and Morphological overlap

5. CMPD • Disease of Adults • Peak Onset 50-70 • 6-9/100,000 • Limited Geographical Based Data

6. PRIMARY THROMBOCYTHAEMIA PLATELETS > 600 X 109/L ^ MEGAKARYOCYTES IN THE MARROW CLONAL DISORDER OF THE MULTIPOTENTIAL STEM CELL

7. Primary Thrombocythaemi - Pathogenesis Aetiology – Unknown Megakaryocytic hyperplasia Functionally abnormal platelets

8. Primary ThrombocythaemiaClinical Features • Asymptomatic • Vasomotor- 40% • Haemorrhage – 25% • Thrombosis – 20% • Splenomegaly • Recurrent Miscarriage

9. PRIMARY THROMBOCYTOSIS DIAGNOSTIC CRITERIA PLATELET COUNT > 600X109/L FOR OVER 2 MONTH WITH NO CAUSE OF REACTIVE THOMBOCYTOSIS, NO EVIDENCE OF PRV, MYELOFIBROSIS, MYELODYSPLASIA AND NO PH CHROMASOME

10. PRIMARY THOMBOCYTOSIS DIAGNOSIS: EXCLUDE CAUSE OF REACTIVE THROMBOCYTOSIS. EG: ACUTE HAEMORRHAGE MALIGNANT DISEASE, CHRONIC INFLAMM DISORDER, ACUTE INFLAM POST-OP SPLENECTOMY EXERCISE IRON DEF.

11. PRIMARY THROMBOCYTHAEMIA TREATMENT MYELOSUPPRESIVE HYROXUREA ANAGRELIDE ANTI-PLATELET AGENTS INTERFERON

12. POLYCYTHAEMIA • Absolute polycythaemia • Relative polycythaemia

13. ABSOLUTE POLYCYTHAEMIA . PRIMARY POLYCYTHAEMIA - POLYCYTHAEMIA RUBRA VERA - ERYTHROPOIETIC RECEPTOR GENE MUTATION. 2. SECONDARY POLYCYTHAEMIA - HYPOXAEMIA POO < 92% - RENAL DISEASE - TISSUE HYPOXIA - HIGH AFFINITY HB - TUMOURS - HEPATOMAS, FIBROIDS, CEREBELLAR - HAEMANGIOBLASTOMAS - HIGH ERYTHROPOIET PRODUCTION 3 IDIOPATHIC ERYTHROCYTOSIS.

14. CLINICAL FEATURES OF P.R.V • Older Age - 50 - 60, Female > Male • Vascular Complications - Arterial = Venous • Cerebral + Coronary - Headache - Dizziness • Due to Small Vessel Occlusion. • => 30-50% - Thrombotic - Art = Venus, Sml & Lrg Vessels • - Haemorrhagic • Peptic Ulceration - ^ Histamine Levels • Prutritis - 20-25% • Skin Change - Pletharic Facies, Acne Roscea,

15. CLINICAL FEATURES OF P.R.V. CONTD. ^ URIC ACID - GOUT ^ BP SPLENOMEGALY - 50% LAB * ^HB ^PCV - MALE - HB 17.5G/L, PCV > 0.51 - FEMALE HB15.5G/L, PCV > 0.46 ^ WCC ^PLATELETS 50% - 400 - 800X 109/L ^ B12 LEUCOCYTE ALKALINE PHOSPHATASE. MARROW - HYPERCELLUAR

16. DIAGNOSTIC CRITERIA OFPPP OR PRV ^RCM > 36ML/KG IN MALES - 32ML/KG IN FEMALES NO EVIDENCE OF A CAUSE OF SECONDARY POLYCYTHAEMIA INCLUDING ARTERIAL OXYGEN SATURATION > 92% + SPLENOMEGALY (PALPABLE) IF (-) SPLENOMEGALY PALPABLE - PLATELET > 400 - ^WCC > 12 - ^ LAP/^B12 COURSE: 15-20% - MYELOFIBROSIS 2-10% - ACUTE LEUKAEMIA RX VENESECTION REGULARILY CHEMOTHERAPY , HYDROXYREA ANTIPLATELET THERAPY

17. Investigation of Polycythaemia • RED CELL MASS STUDIES AIM IS TO INVESTIGATE/EXCLUDE A CAUSE OF SECONDARY POLYCYTHAEMIA • CLINICAL EVALUATION • PULSE OXIMETRY • RENAL - URINALYSIS + RENAL ULTRASOUND • ABDOMINAL ULTRASOUND • NEUTROPHIL COUNT • PLATELET COUNT • MARROW CYTOGENETICS • MARROW CULTURE • SERUM ERYTHROPOIETIN ASSAYS.

18. MANAGEMENT OF P.R.V • PREVENTION OF VASCULAR OCCLUSIONS • DELAY MYELOFIBROTIC TRANSFORMATION • MINIMIZE ACUTE LEUKAEMIC TRANSFORMATION. • PHLEBOTOMY • MYELOSUPPRESSIVE • ANTIPLATELET AGENT.

19. P.R.V. COURSE: 15-20% - MYELOFIBROSIS 2-10% - ACUTE LUEKAEMIA RX: VENESECTION REGULARLY CHEMOTHERAPY 35p HYDROXYURIA ANTIPLATELET THERAPY

20. MYELOFIBROSIS(agnogenic myeloid metaplasia) 1o DISORDER - OR - AS PART OF OTHER MYELOPROLIFERATIVE DISORDERS 20% HAVE HX OF PRV 2ND LYMPHOPROLIFERATIVE, BENZENE, FLUORINE, ANSENIC

21. MYELOFIBROSIS(agnogenic myeloid metaplasia) PATHOLOGY: ^ Connective tissue within the bone marrow. ^ Collagen ^ New bone formation destruction of normal marrow microenvironment ^ circ stem cells: cells normally present in the marrow Dysplastic Feature. Extramedullary haemopoiesis - eg. liver.

22. MYELOFIBROSIS(agnogenic myeloid metaplasia) SYMPTOMS: OFTEN ASYMPTOMATIC: BONE MARROW FAILURE ^ SPLEEN - LUQ PAIN METABOLIC CONSEQUENCE OF M/P DISORDER - SWEATS ^URIC ACID GOUT, RENAL COLIC BLEEDING DIATHESIS

23. Myeloproliferative DisordersChronic Granulocytic Leukaemia • First malignancy associated with a recurring chromosomal abnormality • Translocation of genetic material from chromosomes 9 22 • Fusion gene fusion protein - pathogenesis

24. CHRONIC GRANULOCYTIC LEUKAEMIA = CHRONIC MYELOID LEUKAEMIA 1/100,000 MALE > FEMALE 5TH - 6TH DECIDE BUT CAN OCCUR AT ANY AGE PH CHROMOCOSME - RECIPROCAL TRANSLOCATION BETWEEN CHROMOSOME 9 => 22 = ? AETIOLOGICAL SIGNIFICANCE OR ? MARKER DISEASE. => CLONAL DISORDER OF HAEMOPOIETIC STEM CELL ? PROCESS - GROWTH ADVANTAGE => X 30 FIELD ^ IN GRANULOCTE MASS

25. C.G.L. CLINICAL FEATURES: BIPHASIC OR TIRPHASIC DISEASE CRONIC ACCELERATED TRANSFORMATION 20% ASYMPTOMATIC NON-SPECIFIC COMPLAINTS SPLENAMEGALY AND HEPATOMEGALY

26. C.G.L. LAB FEATURES: LEUCOCYTOSIS - 100 -300 x 109/L. BASOPHILIA THROMBOCYTOSIS HYPERCELLULAR MARROW PH POSITIVE IN 90% INCREASED MARROW FIBROSIS.

27. C.G.L. TREATMENT OF C.G.L: BONE MARROW TRANSPLANT CYTOREDUCTIVE THERAPY TYROSINE KINASE INHIBITORS E.G. HYDROXYUREA, INTERFERON MANAGEMENT OF METABOLIC COMPLICATIONS.