1. Armaan Khalid

2. What is Leukaemia?  Cancer of the blood or bone marrow  Can be classified: Acute/chronic Myeloid/lymphoid

3. Classification of Leukaemias Leukaemia AcuteChronic ALLAMLCLLCML

4. Aetiology  ???  Radiation Survivors of Hiroshima & Nagasaki  Chemicals & drugs Benzene, melphalan  Genetic Down’s, Klinefelter’s  Viruses Human T-cell lymphotropic virus type 1 (HTLV-1)

5. Pic of cell lineage

6. Acute Lymphoblastic Leukaemia  Malignant disease of BM in which early lymphoid precursors (lymphoblast) proliferate & replace normal haematopoetic cells  Normally due to chromosomal translocations  Lymphoblasts replace normal bone marrow production Anaemia Neutropaenia Thrombocytopaenia

7. Acute Myelogenous Leukaemia  Uncontrolled proliferation of myeloblasts in the bone marrow Bone marrow overcrowding → failure  ♀<♂, affects all ages (↑↑↑ % with age)  Commonly due to Chromosomal translocations Genetic abnormalities (Down’s) Radiation & chemical exposure (benzene) Past exposure to chemo agents ○ Cancer survivors Antecedent haematological disorder ○ Myelodysplastic Syndromes

8. ALL/AML Presentation  ALL: Most common paeds malignancy  Hx/Ex Fever Fatigue/dizziness/palpitations/dyspnoea Bleeding/Ecchymoses/Petechiae Bone pain Hepatosplenomegaly

9. ALL/AML Workup  Ix FBE/LDH/LFT/UNE Peripheral blood film ○ Circulatory blast cells Blood Culture X-Ray/CT Bone marrow aspiration & biopsy ○ Blast cells > 20% Flow cytometry

10. ALL/AML Mgmt  Chemotherapy Induction Consolidation Maintenance CNS prophylaxis (esp. ALL) ○ Risk of meningeal leukaemia @ diagnosis/relapse  FCR regimen Fludarabine Cyclophosphamide Rituximab  G-CSF usage  BM transplantation

11. Acute Promyelocytic Leukaemia  APML is a subtype of AML  Can be considered a medical emergency  Commonly assoc w coagulopathy due to DIC & fibrinolysis  Rule out by doing a peripheral blood smear

12. Febrile Neutropaenia  Essential to monitor neutrophil count  Neutropaenia + Fever = Febrile Neutropaenia  Mgmt Admit & isolate Symptomatic Rx Cease chemoRx Broad spectrum Abx ○ E.g. Ticarcillin + Gentamicin ?CSF administration

13. Chronic Lymphocytic Leukaemia  Commonest Leukaemia (↑↑↑% in ↑ age) Accumulation of functionally incompetent lymphocytes  Identical to Small Lymphocytic Lymphoma Peripheral blood lymphocytosis > 4000 cells/mm 3 ○ CLL  Almost always B lymphocytic in origin  Many pts are asymptomatic Others present with BM failure & immunosuppresion

14. CLL Presentation  Hx/Ex Anaemia (AI haemolytic anaemia) Fever Generalised lymphadenopathy Hepatosplenomegaly Recurrent infection Bleeding/Ecchymoses/Petechiae

15. CLL Workup  Ix FBE/LDH/LFT/UNE Peripheral blood film ○ Lymphocytosis > 5 x 10 9 /L for more 3 mth ○ Smudge cells Blood Culture X-Ray/CT Bone marrow aspiration & biopsy ○ Blast cells > 20% Flow cytometry Lymph node biopsy

16. Smudge cells in CLL

17. CLL Mgmt  When to treat (Absolute indications) Anaemia Recurrent infection Splenic discomfort X2 lymphocyte count w/in 6 mth  ChemoRx FCR/CHOP  BM transplantation  Transformation to more aggro tumours Poor prognosis

18. Chronic Myelogenous Leukaemia  Acquired abnormality that involves the haematopoetic stem cell  Characterised by ↑ proliferation of the granulocytic cell line w/out the loss of their ability to differentiate On peripheral blood: ↑ granulocyte & its precursors w occasional blast cells  Philadelphia chromosome (9:22)  Almost always in adults (peak 40-60y/o)  Runs a slowly progressive course Chronic phase Accelerated phase Blast crisis (Fatal)

19. CML Blast Crisis  After 3-5 years, CML may evolve into a blast crisis ↑↑↑ BM or peripheral blood blast count  Manifestation similar to acute leukaemia  Usual medication are unable to control leukocytosis & splenomegaly  2/3 of cases are myeloid in nature  Accelerated phase may last 3-6 months prior to blast crisis

20. Philadelphia chromosome

21. Philadelphia chromosome 101  Reciprocal translocation of b/w long arms of chromosomes 9 & 22 Translocation causes relocation of abl oncogene (9) to the BCR region (22) ○ BCR/ABL fusion gene  Hallmark of CML however, can be found in other diseases (ALL)

22. CML Presentation  Hx/Ex Tiredness/Fatigue/LOW/Malaise Hepatosplenomegaly Low-grade fever & sweating Anaemia Lymphadenopathy

23. CML Workup  Ix FBE/LDH/LFT/UNE ○ ↓ Leukocyte alkaline phosphatase Peripheral blood film ○ ↑ Granulocytes w myeloid precursors ○ Presence of different mid-stage progenitor cells Blood Culture X-Ray/CT Bone marrow aspiration & biopsy ○ ↑ cellularity & myeloid precursors Cytogenetic studies (Philadelphia chromosome) Lymph node biopsy

24. CML Mgmt  Goal 1. Haematological remission ○ Normal FBE 2. Cytogenetic remission ○ 0% Ph-positive cells 3. Molecular remission ○ Negative PCR for BCL/ABL gene  Imatinib (Gleevec) Inhibits proliferation & induces apoptosis by inhibiting tyrosine kinase activity in cells positive for BCR/ABL fusion gene Useful in Chronic phase

25. CML Mgmt  Stem cell transplantation  Hydroxyurea Myelosuppressive agent used to achieve haematological remission  Busulfan  Interferon  Splenectomy Useful in pts with large & painful spleens, not managed well on medications