MYELOPROLIFERATIVE DISEASES By DR. KAMAL E. HIGGY CONSULTANT HAEMATOLOGIST

1. MYELOPROLIFERATIVE DISEASES ByDR. KAMAL E. HIGGYCONSULTANT HAEMATOLOGIST

2. WHO Classification Chronic Myeloproliferative Disease --------------------------------------------------------------------------------------------------------------------------- Chronic Myelogenous Leukaemia [Ph chromosome, t(9;22)(q34;q11), BCR/ABL- positive ] Chronic Neutrophilic Leukaemia Chronic Eosinophilic Leukaemia (and the hypereosinophilic syndrome) Polycythaemia Vera Chronic Idiopathic Myelofibrosis (with extramedullary haematopoiesis) Essential Thrombocythaemia Chronic Myeloproliferative Disease, Unclassifiable

3. WHO Classification Myelodysplastic / Myeloproliferative Diseases ----------------------------------------------------------------- Chronic Myelomonocytic Leukaemia Atypical Chronic Myeloid Leukaemia Juvenile Myelomonocytic Leukaemia Myelodysplastic/Myeloproliferative Disease, Unclassifiable

5. Myeloid Disorders Usual Features at Diagnosis

6. Myeloproliferative Disease Recurring Genetic Abnormalities and Their Frequency (%) at diagnosis

7. Chronic Granulocytic Leukaemia Presenting Manifestations ---------------------------------------------------------------------------- Common Anaemia Splenomegaly Less Common Symptoms due to the raised metabolic rate Haemorrhagic Manifestations, especially bruising

8. Chronic Granulocytic Leukaemia Occasional Presenting Manifestations ---------------------------------------------------------------------------- Acute abdominal pain Bone or joint pains. Menstrual disturbances. Neurological symptoms Priapism Gout Skin disorder Disturbances of vision or hearing Accidental discovery on routine blood examination.

9. Chronic Granulocytic Leukaemia Evolution of the disease ------------------------------------------------------------ Chronic Phase Accelerated Phase Blastic Transformation (AML) (ALL)

10. Chronic Myeloid Leukaemia Laboratory Investigations ----------------------------------------------------------------------------------------------------------------------------------------------- C.B.C. Neutrophil Alkaline Phosphatase. Bone Marrow Examination. Serum B12 & B12 binding capacity. Cytogenetic Studies (Ph1) chromosome [ t ( 9 : 22 ) ] DNA restriction enzyme analysis BCR (Breakpoint Cluster Region)

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17. Chronic Myeloid Leukaemia  Accelerated Phase Blasts 10% to 19% of peripheral blood white cells or bone marrow cells Peripheral blood basophiles at least 20% Persistent thrombocytopenia (<100X109/L) unrelated to therapy, or persistent thrombocytosis (> 1000X109L) unresponsive to therapy Increasing spleen size and increase WBC count unresponsive to therapy.

18. Chronic Myeloid Leukaemia  Accelerated Phase (Continued) Cytogenetic evidence of clonal evolution (i.e., the appearance of an additional genetic abnormality that was not present in the initial specimen at the time of diagnosis of chronic phase CML). Megakaryocytic proliferation in sizable sheets and clusters, associated with marked reticulin or collagen fibrosis, and/or severe granulocytic dysplasia, should be considered as suggestive of CML-AP. These findings have not yet been analyzed in large clinical studies, however, so it is not clear if they are independent criteria for accelerated phase. They often occur simultaneously with one or more of the other features listed.

19. Chronic Myeloid Leukaemia Blastic Phase (BP) This Phase is diagnosed if one or more of following is present: Blasts 20% or more of peripheral blood white cells or bone marrow cells Extramedullary blast proliferation Large foci or clusters of blasts in bone marrow biopsy

24. FAP Proposal Guidelines for distinguishing Chronic Granulocytic (CGL), atypical Chronic Myeloid (aCML) and Chronic Myelomonocytic Leukaemia (CMML)

25. Chronic Myeloid Leukaemia Chronic Phase Treatment ------------------------------------------------------------------------------------------------------------------------------------------------ Hydroxyurea (HU): WBC/ul HU (mg/kg BW/DAY) >50,000 50 15-50,000 30 – 40 <15,000 25 Busulphan Alpha – Interferon: 5 MU/DAY 7.5 MU/DAY if WBC > 10,000/mcl 10 MU/DAY if WBC > 20,000/mcl 3 MU/DAY if cytopenia develops - BMT, ABMT & STEM CELL HARVEST - Gleevec