Armaan Khalid
What is Leukaemia? Cancer of the blood or bone marrow Can be classified: Acute/chronic Myeloid/lymphoid
Classification of Leukaemias Leukaemia AcuteChronic ALLAMLCLLCML
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)
Pic of cell lineage
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
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
ALL/AML Presentation ALL: Most common paeds malignancy Hx/Ex Fever Fatigue/dizziness/palpitations/dyspnoea Bleeding/Ecchymoses/Petechiae Bone pain Hepatosplenomegaly
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
ALL/AML Mgmt Chemotherapy Induction Consolidation Maintenance CNS prophylaxis (esp. ALL) ○ Risk of meningeal diagnosis/relapse FCR regimen Fludarabine Cyclophosphamide Rituximab G-CSF usage BM transplantation
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
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
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
CLL Presentation Hx/Ex Anaemia (AI haemolytic anaemia) Fever Generalised lymphadenopathy Hepatosplenomegaly Recurrent infection Bleeding/Ecchymoses/Petechiae
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
Smudge cells in CLL
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
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)
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
Philadelphia chromosome
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)
CML Presentation Hx/Ex Tiredness/Fatigue/LOW/Malaise Hepatosplenomegaly Low-grade fever & sweating Anaemia Lymphadenopathy
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
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
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