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STEM CELL DISORDERS WHEREBY YOU GET ABNORMAL

PROLIFERATION IN ONE OR MORE CELL LINE DERIVED FROM A

COMMON STEM CELL

Myeloproliferative Disorder

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THE INDIVIDUAL FEATURE OF THESE DISEASES RESULT FROM A:

•DISTURBED HAEMOPOIETIC MICROENVIRONMENT

•CLONAL ABNORMALITY

•DISTURBANCE IN HAEMOPOIETIC REGULATION.

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Myeloproliferative Disorder

• Polycythaemia Ruba Vera

• Myelofibrosis

• Primary Thrombocytopenia

• Chronic Myeloid Leukaemia

• Myeloproliferative Disorder – unclassifiable

• Chronic Eosinophilic Leukaemia

• Chronic Myeloid Leukaemia

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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

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CMPD

• Disease of Adults

• Peak Onset 50-70

• 6-9/100,000

• Limited Geographical Based Data

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PLATELETS > 600 X 109/L

^ MEGAKARYOCYTES IN THE MARROW

CLONAL DISORDER OF THE MULTIPOTENTIAL STEM CELL

PRIMARY THROMBOCYTHAEMIAPRIMARY THROMBOCYTHAEMIA

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Primary Thrombocythaemi - Pathogenesis

Aetiology – Unknown

Megakaryocytic hyperplasia

Functionally abnormal platelets

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Primary ThrombocythaemiaClinical Features

• Asymptomatic

• Vasomotor- 40%

• Haemorrhage – 25%

• Thrombosis – 20%

• Splenomegaly

• Recurrent Miscarriage

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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

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PRIMARY THOMBOCYTOSIS

DIAGNOSIS:EXCLUDE CAUSE OF REACTIVE THROMBOCYTOSIS.EG: ACUTE HAEMORRHAGEMALIGNANT DISEASE,CHRONIC INFLAMMDISORDER, ACUTE INFLAMPOST-OP SPLENECTOMYEXERCISE IRON DEF.

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PRIMARY THROMBOCYTHAEMIA

TREATMENT

MYELOSUPPRESIVE HYROXUREA ANAGRELIDE

ANTI-PLATELET AGENTS

INTERFERON

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POLYCYTHAEMIA

• Absolute polycythaemia

• Relative polycythaemia

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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.

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• 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

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CLINICAL FEATURES OF P.R.V. CONTD.

^ URIC ACID - GOUT^ BPSPLENOMEGALY - 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

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^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/^B12COURSE: 15-20% - MYELOFIBROSIS 2-10% - ACUTE LEUKAEMIARX VENESECTION REGULARILY CHEMOTHERAPY , HYDROXYREA ANTIPLATELET THERAPY

DIAGNOSTIC CRITERIA OFPPP OR PRV

DIAGNOSTIC CRITERIA OFPPP OR PRV

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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.

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• PREVENTION OF VASCULAR OCCLUSIONS• DELAY MYELOFIBROTIC

TRANSFORMATION• MINIMIZE ACUTE LEUKAEMIC

TRANSFORMATION.• PHLEBOTOMY• MYELOSUPPRESSIVE• ANTIPLATELET AGENT.

MANAGEMENT OF P.R.VMANAGEMENT OF P.R.V

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P.R.V.

COURSE:

15-20% - MYELOFIBROSIS

2-10% - ACUTE LUEKAEMIA

RX:

VENESECTION REGULARLY

CHEMOTHERAPY 35p HYDROXYURIA

ANTIPLATELET THERAPY

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MYELOFIBROSIS(agnogenic myeloid metaplasia)1o DISORDER

- OR - AS PART OF OTHER MYELOPROLIFERATIVE DISORDERS

20% HAVE HX OF PRV

2ND LYMPHOPROLIFERATIVE, BENZENE, FLUORINE, ANSENIC

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MYELOFIBROSIS(agnogenic myeloid metaplasia)PATHOLOGY:^ Connective tissue within the bone marrow.^ Collagen^ New bone formationdestruction of normal marrow microenvironment^ circ stem cells: cells normally present in the

marrow Dysplastic Feature.Extramedullary haemopoiesis - eg. liver.

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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

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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

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CHRONIC GRANULOCYTIC LEUKAEMIA = CHRONIC MYELOID LEUKAEMIA

1/100,000 MALE > FEMALE5TH - 6TH DECIDE BUT CAN OCCUR AT ANY AGEPH CHROMOCOSME - RECIPROCAL

TRANSLOCATION BETWEEN CHROMOSOME9 => 22 = ? AETIOLOGICAL SIGNIFICANCE OR ?

MARKER DISEASE.=> CLONAL DISORDER OF HAEMOPOIETIC STEM

CELL ? PROCESS - GROWTH ADVANTAGE=> X 30 FIELD ^ IN GRANULOCTE MASS

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CLINICAL FEATURES:

BIPHASIC OR TIRPHASIC DISEASE

CRONIC ACCELERATED

TRANSFORMATION

20% ASYMPTOMATIC

NON-SPECIFIC COMPLAINTS

SPLENAMEGALY AND HEPATOMEGALY

C.G.L.

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C.G.L.

LAB FEATURES:

LEUCOCYTOSIS - 100 -300 x 109/L.

BASOPHILIA

THROMBOCYTOSIS

HYPERCELLULAR MARROW

PH POSITIVE IN 90%

INCREASED MARROW FIBROSIS.

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C.G.L.

TREATMENT OF C.G.L:BONE MARROW TRANSPLANTCYTOREDUCTIVE THERAPY TYROSINE KINASE INHIBITORSE.G. HYDROXYUREA, INTERFERONMANAGEMENT OF METABOLIC

COMPLICATIONS.