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