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Armaan Khalid. Leukaemia 101. What is Leukaemia?. Cancer of the blood or bone marrow Can be classified: Acute/chronic Myeloid/lymphoid. Classification of Leukaemias. Leukaemia. Acute. Chronic. ALL. AML. CLL. CML. Aetiology. ??? Radiation Survivors of Hiroshima & Nagasaki - PowerPoint PPT Presentation
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LEUKAEMIA 101Armaan Khalid
What is Leukaemia? Cancer of the blood or bone marrow Can be classified:
Acute/chronicMyeloid/lymphoid
Classification of Leukaemias
Leukaemia
Acute Chronic
ALL AML CLL CML
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
productionAnaemiaNeutropaeniaThrombocytopaenia
Acute Myelogenous Leukaemia Uncontrolled proliferation of myeloblasts in the
bone marrowBone marrow overcrowding → failure
♀<♂, affects all ages (↑↑↑ % with age) Commonly due to
Chromosomal translocationsGenetic abnormalities (Down’s)Radiation & chemical exposure (benzene)Past exposure to chemo agents
○ Cancer survivorsAntecedent haematological disorder
○ Myelodysplastic Syndromes
ALL/AML Presentation ALL: Most common paeds malignancy Hx/Ex
FeverFatigue/dizziness/palpitations/dyspnoeaBleeding/Ecchymoses/PetechiaeBone painHepatosplenomegaly
ALL/AML Workup Ix
FBE/LDH/LFT/UNEPeripheral blood film
○ Circulatory blast cellsBlood CultureX-Ray/CTBone marrow aspiration & biopsy
○ Blast cells > 20%Flow cytometry
ALL/AML Mgmt Chemotherapy
InductionConsolidationMaintenanceCNS prophylaxis (esp. ALL)
○ Risk of meningeal leukaemia @ diagnosis/relapse FCR regimen
FludarabineCyclophosphamideRituximab
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 & isolateSymptomatic RxCease chemoRxBroad spectrum Abx
○ E.g. Ticarcillin + Gentamicin?CSF administration
Chronic Lymphocytic Leukaemia Commonest Leukaemia (↑↑↑% in ↑ age)
Accumulation of functionally incompetent lymphocytes
Identical to Small Lymphocytic LymphomaPeripheral blood lymphocytosis > 4000 cells/mm3
○ 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)FeverGeneralised lymphadenopathyHepatosplenomegalyRecurrent infectionBleeding/Ecchymoses/Petechiae
CLL Workup Ix
FBE/LDH/LFT/UNEPeripheral blood film
○ Lymphocytosis > 5 x 109/L for more 3 mth○ Smudge cells
Blood CultureX-Ray/CTBone marrow aspiration & biopsy
○ Blast cells > 20%Flow cytometryLymph node biopsy
Smudge cells in CLL
CLL Mgmt When to treat (Absolute indications)
AnaemiaRecurrent infectionSplenic discomfortX2 lymphocyte count w/in 6 mth
ChemoRxFCR/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 & 22Translocation 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/MalaiseHepatosplenomegalyLow-grade fever & sweatingAnaemiaLymphadenopathy
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 CultureX-Ray/CTBone marrow aspiration & biopsy
○ ↑ cellularity & myeloid precursorsCytogenetic 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