Leukaemia
Types
Chronic lymphocytic leukaemia
Acute myeloid leukaemia
Acute lymphoblastic leukaemia
Chronic myeloid leukaemia
Acute Lymphoblastic Leukaemia
Definition
Malignancy of lymphoid cells, affecting B or T cell lines
Epidemiology
Rare in adults
70-90% cure rate in children
Commonest cancer of childhood
40% cure rate in adults
Aetiology
Triggers include ionizing radiation, pregnancy and Down's syndrome
Develops from genetic susceptibility combined with an environmental trigger
Pathophysiology
Arrests maturation and promotes uncontrolled proliferation of immature blast cells
There is bone marrow failure and tissue infiltration
Signs
Poor prognosis for those with Philadelphia chromosome
Lymphadenopathy - due to infiltration
Common infections e.g. measles, candidiasis, pneumocystis pneumonia
Splenomegaly - due to infiltration
Anaemia
Hepatomegaly - due to infiltration
Investigations
Bone marrow aspirate - blast cells are seen
Chext x-ray and CT for abdominal lymphadenopathy
Blood film - blast cells are seen
Lumbar puncture to assess CNS involvement
Low WCC and low platelets
Treatment
IV antibiotics
Chemotherapy
IV fluids
Allopurinol to prevent tumour lysis
Blood transfusion
Susceptible to infections due to neutropenia
Marrow transplantations if disease is in remission - for young adults
Acute Myeloid Leukaemia
Definition
Neoplastic proliferation of blast cells derived from marrow myeloid elements
Aetiology
Can be a consequence of long term chemo for lymphoma
Radiation
Down's syndrome
Epidemiology
Most common acute leukaemia in adults
Incidence increases with age
Signs
Infection
Gum hypertrophy
Anaemia
Skin involvement
Hepatosplenomegaly
Investigations
Bone marrow biopsy
Auer rods are diagnostic of AML
WCC is often high
Treatment
Bone marrow transplant - pluripotent stem cells collected from marrow
Allogenic bone marrow transplant is from HLA-matched siblings during 1st remission of disease
Walking alleviates fatigue
Cyclophosphamide is given to destroy leukaemic cells and immune system and is then repopulated with transplant
Chemotherapy - intensive prolonged periods of marrow suppression, neutropenia and low platelets
Progresses rapidly - death in 2 months if untreated
Chronic Myeloid Leukaemia
Definition
= Uncontrolled clonal proliferation of myeloid cells
If untreated, chronic phase lasts 3-4 years followed by blast transformation with development of acute leukaemia and rapid death
Aetiology
Philadelphia chromosome is present in >80% of patients
Philadelphia chromosome is a hybrid chromosome where is this reciprocal translocation between the long arms of chromosomes 9-12
Epidemiology
Accounts for 15% of leukaemias
Affects 40-60 year olds
Higher incidence in males than females
Rare in childhood
Symptoms
Fever
Sweats
Fatigue
Gout
Weight loss
Bleeding due to platelet dysfunction
Signs
Splenomegaly - >75%
Anaemia
Hepatomegaly
Bruising
Investigations
Hb is low/normal
Bone marrow biopsy - hypercellular
WBC significantly raised
Cytogenic analysis of bone marrow to detect Philadelphia chromosome
Treatment
Stem cell transplant - carries significant morbidity and mortality but is the only cure. Should only be used as 1st line treatment in young patients only
Imatinib - a specific tyrosine kinase inhibitor which targets the genes
Chronic Lymphocytic Leukaemia
Definition
Accumulation of mature B cells which have escaped from programmed cell death
Incurable disease of older people
1/3 never progress, 1/3 progress slowly and 1/3 progress actively
Death is often due to a complication e.g. infection
Aetiology
Mutation
Pneumonia can trigger
Epidemiology
Most common leukaemia
M:F = 2:1
Symptoms
Weight loss
Sweats
Asymptomatic
Signs
Enlarged, rubbery non-tender nodes
Hepatosplenomegaly
Anaemia
Investigations
FBC shows marked raised lymphocytes
Low Hb, neutrophils and platelets
Treatment
Radiotherapy for lymphadenopathy and splenomegaly
Supportive care - transfusions + IV human immunoglobulin
Fludarabine + cyclophosphamide + rituximab (these are synergistic)
Stem cell transplant