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