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

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

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

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

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

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

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

Primary Thrombocythaemia Clinical Features Asymptomatic Vasomotor- 40% Haemorrhage – 25% Thrombosis – 20% Splenomegaly Recurrent Miscarriage

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

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

PRIMARY THROMBOCYTHAEMIA TREATMENT MYELOSUPPRESIVE HYROXUREA ANAGRELIDE ANTI-PLATELET AGENTS INTERFERON

POLYCYTHAEMIA Absolute polycythaemia Relative polycythaemia

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.

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,

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

DIAGNOSTIC CRITERIA OF PPP 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

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.

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

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

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

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.

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

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

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

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

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

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