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

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Myeloproliferative Disorder

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

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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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PRIMARY THROMBOCYTHAEMIA

• PLATELETS gt 600 X 109/L
• MEGAKARYOCYTES IN THE MARROW
• CLONAL DISORDER OF THE MULTIPOTENTIAL STEM CELL

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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 gt 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 HAEMORRHAGE
• MALIGNANT DISEASE,
• CHRONIC INFLAMM
• DISORDER,
• ACUTE INFLAM
• POST-OP SPLENECTOMY
• EXERCISE
• 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 lt 92
• - RENAL DISEASE
• - TISSUE HYPOXIA - HIGH AFFINITY HB
• - TUMOURS - HEPATOMAS, FIBROIDS, CEREBELLAR
• - HAEMANGIOBLASTOMAS
• - HIGH ERYTHROPOIET PRODUCTION
• 3 IDIOPATHIC ERYTHROCYTOSIS.

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CLINICAL FEATURES OF P.R.V

• Older Age - 50 - 60, Female gt Male
• Vascular Complications - Arterial Venous
• Cerebral Coronary - Headache - Dizziness
• Due to Small Vessel Occlusion.
• gt 30-50 - Thrombotic - Art Venus, Sml Lrg
  Vessels
• - Haemorrhagic
• Peptic Ulceration - Histamine Levels
• Prutritis - 20-25
• Skin Change - Pletharic Facies, Acne Roscea,

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CLINICAL FEATURES OF P.R.V. CONTD.

• URIC ACID - GOUT
• BP
• SPLENOMEGALY - 50
• LAB HB PCV - MALE - HB 17.5G/L, PCV gt 0.51
• - FEMALE
  HB15.5G/L, PCV gt 0.46
• WCC
• PLATELETS 50 - 400 - 800X 109/L
• B12
• LEUCOCYTE ALKALINE PHOSPHATASE.
• MARROW - HYPERCELLUAR

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DIAGNOSTIC CRITERIA OFPPP OR PRV

• RCM gt 36ML/KG IN MALES - 32ML/KG IN FEMALES NO
  EVIDENCE OF A CAUSE OF SECONDARY POLYCYTHAEMIA
  INCLUDING ARTERIAL OXYGEN SATURATION gt 92
• SPLENOMEGALY (PALPABLE)
• IF (-) SPLENOMEGALY PALPABLE - PLATELET gt 400
• -
  WCC gt 12
• -
  LAP/B12
• COURSE 15-20 - MYELOFIBROSIS
• 2-10 - ACUTE LEUKAEMIA
• RX VENESECTION REGULARILY
• CHEMOTHERAPY , HYDROXYREA
• ANTIPLATELET THERAPY

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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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MANAGEMENT OF P.R.V

• PREVENTION OF VASCULAR OCCLUSIONS
• DELAY MYELOFIBROTIC TRANSFORMATION
• MINIMIZE ACUTE LEUKAEMIC TRANSFORMATION.
• PHLEBOTOMY
• MYELOSUPPRESSIVE
• ANTIPLATELET AGENT.

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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 formation
• destruction 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 gt FEMALE
• 5TH - 6TH DECIDE BUT CAN OCCUR AT ANY AGE
• PH CHROMOCOSME - RECIPROCAL TRANSLOCATION BETWEEN
  CHROMOSOME
• 9 gt 22 ? AETIOLOGICAL SIGNIFICANCE OR ? MARKER
  DISEASE.
• gt CLONAL DISORDER OF HAEMOPOIETIC STEM CELL
• ? PROCESS - GROWTH ADVANTAGE
• gt X 30 FIELD IN GRANULOCTE MASS

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C.G.L.

• CLINICAL FEATURES
• BIPHASIC OR TIRPHASIC DISEASE
• CRONIC ACCELERATED
• TRANSFORMATION
• 20 ASYMPTOMATIC
• NON-SPECIFIC COMPLAINTS
• SPLENAMEGALY AND HEPATOMEGALY

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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 TRANSPLANT
• CYTOREDUCTIVE THERAPY
• TYROSINE KINASE INHIBITORS
• E.G. HYDROXYUREA,
• INTERFERON
• MANAGEMENT OF METABOLIC COMPLICATIONS.