armaan khalid. what is leukaemia? cancer of the blood or bone marrow can be classified:...
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What is Leukaemia?
Cancer of the blood or bone marrow Can be classified:
Acute/chronicMyeloid/lymphoid
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)
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
IxFBE/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 regimenFludarabineCyclophosphamideRituximab
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 Lymphoma
Peripheral 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/ExAnaemia (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
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 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/ExTiredness/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