Haematological malignancies

These are malignant proliferations of:

• Lymphocytes
• Hodgkin's disease
• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukaemia
• Myeloma (plasma cells)
• Immature lymphocytes
• Acute lymphoblastic leukaemia
• Hairy cell leukaemia
• Myeloma cells
• Acute myelogenous leukaemia
• Chronic myeloid leukaemia

Lymphomas

Hodgkin's disease

• B or T cell malignant clone

Clinical features

• Lymphadenopathy
• Fever
• Drenching sweats B symptoms
• Weight loss
• Alcohol-induced pain
• Hepatomegaly
• Splenomegaly

Investigations

• Blood count - anaemia
• ESR increased
• Uric acid sometimes increased
• Chest X-ray - mediastinal mass or hilar lymph nodes
• CT scan
• Lymphadenopathy
• Liver or spleen enlargement or infiltration
• Lymph node biopsy and histology
• Bone marrow biopsy (shows Sternberg-Reed cells)

Management

• Depends on
• Stage and histology
• Site of tumour
• Presence of B symptoms
• Radiotherpay
• Chemotherapy
• Myeloablation and stem cell support

Prognosis

• 40-70% survival at 20 years
• Depends on stage of original tumour

Non-Hodgkin's lymphoma

• 70% B cell
• Associated with EBV and HIV infection

Clinical features

• Lymphadenopathy
• Symptoms due to site of tumour
• May involve GI tract, lungs, brain

Investigations

• Blood count
• Anaemia
• Thrombocytopenia
• Liver chemistry
• Chest X-ray
• CT scan of abdomen and thorax
• Bone marrow biopsy
• Lymph node biopsy

Management

• Depends on grade
• Radiotherapy
• Chemotherapy

Burkitt's lymphoma

• Associated with Epstein-Barr virus
• Endemic in West Africa
• Jaw, abdominal and ovarian tumours
• Curable

Acute leukaemias

Epidemiology

• Rare: 5 in 100000

Aetiology

• Unknown in most cases
• T-cell leukaemia - retrovirus (HTLV-1)
• Specific genetic mutations
• Chromosome translocations, e.g. t (15;17)
• Environment factors
• Ionizing radiation

Clinical features

• Bone marrow failure
• Weakness and tiredness due to anaemia
• Bruising due to thrombocytopenia
• Repeated infections

Investigations

• Blood count
• Blood film - leukaemic blast cells
• Bone marrow - blast cells

Management

• Correct anaemia and thrombocytopenia
• Treat any infection
• Chemotherapy to achieve remission
• Myeloablation with stem cell support to clear marrow of malignant cells

Acute myeloid leukaemia (AML)

• Classified by cell type
• 70% alive at 1 year -> 30% alive at 5 years
• Treatment aims for complete remission
• Followed by bone marrow ablation

Acute lymphoblastic leukaemia (ALL)

• Predominantly a disease of children
• Cure rate 50-60% in children, 30% in adults
• Central nervous system involvement common
• Prophylactic intrathecal chemotherapy

Chronic leukaemia

• Chronic leukaemias occur in older patients, most of whom die within 5 years of the diagnosis
• Clinical course consists of a chronic illness lasting 3-4 years, followed by transformation into an acute leukaemia or sometimes myelofibrosis in the case of chronic myeloid leukaemia

Chronic myeloid leumaemia (CML)

Clinical features

• Anaemia
• Night sweats and fever
• Weight loss
• Splenomegaly -> pain

Investigations

• Blood count - raised white count
• Multiple myeloid precursors
• Bone marrow biopsy
• Genetic testing for the Philadelphia chromosome (9:22 translocation) (positive in 90-95%)

Management

• Interferons -> remissions in 10%
• Hydroxyurea reduces white cell count
• Myeloablation with bone marrow transplant

Chronic lymphocytic leukaemia (CLL)

Clinical features

• Often an incidental finding
• Infections due to neutropenia
• Anaemia (may be due to haemolysis)
• Lymphadenopathy
• Hepatosplenomegaly

Investigations

• Haemoglobin low or normal
• White count > 15 x 10^9 / L
• 40% lymphocytes
• Platelets low or normal
• Serum immunoglobulins may be low

Management

• Nothing if asymptomatic
• Steroids for haemolysis
• Fludarabine or chlorambucil

Hairy cell leukaemia

• Rare
• Usually a B cell tumour
• Cells have filament-like projections

Myeloproliferative disorders

• Uncontrolled proliferation of a blood cell line
• Can transform into acute leukaemias or from myeloproliferation to another

Polycythaemia vera

• Red cell proliferation
• Patients usually >60 years old

Clinical features

• Tiredness
• Depression
• Tinnitus
• Vertigo
• Visual disturbance
• Itching after a hot bath
• Gout (due to increased cell turnover)
• Thrombosis or haemorrhage
• Plethora and cyanosis
• Splenomegaly

Investigations

• Haemoglobin raised
• Packed cell volume (haematocrit) increased
• 50% have increased platelets
• 75% have increased white cells
• Uric acid increased
• Leucocyte alkaline phosphatase increased

Management

• Venesection
• Chemotherapy
• Allopurinol to avoid gout

Prognosis

• 30% -> myelofibrosis
• 5% -> AML

Essential thrombocythaemia

• Platelet count > 1000 x 10^9 / L
• Bruising and bleeding (poor platelet function)
• Increased risk of thrombosis

Myelofibrosis

• Stem cell proliferation
• Bone marrow fibrosis

Clinical features

• Anaemia
• Weight loss
• Splenomegaly
• Bone pain
• Gout

Investigations

• Anaemia
• High platelets
• 'Dry' bone marrow aspirate
• High uric acid

Management

• Blood transfusion
• Folic acid
• Chemotherapy and radiotherapy
• Splenectomy may be required

Prognosis

• 10-20% -> AML

Myelodysplasia

• Stem cell defects
• Bone marrow failure
• Abnormal red cells, leucocytes and platelets

Management

• Supportive therapy
• Low-intensity chemotherapy

Multiple myeloma and hyperglobulinaemia

• Clonal expansion of plasma cells resulting in very high production of a single immunoglobulin (paraprotein) or an immunoglobulin component

Myeloma

• Elderly patients

Clinical features

• Bone lesions -> pain and fractures
• Hypercalcaemia
• Bone marrow infiltration
• Anaemia, neutropenia
• Renal impairment
• Hyperviscosity syndrome

Investigations

• Blood count (anaemia, low white cells)
• Elevated ESR and CRP
• Elevated calcium, urea, and creatinine
• Protein electrophoresis - monoclonal band
• Skeletal X-ray survey - lytic lesions, e.g. skull
• 24-hour urine for light chain proteins
• Bone marrow aspirate - plasma cells

Management

• Supportive treatment
• Steroids and radiotherapy for bone lesions
• Chemotherapy

Waldenstrom's macroglobulinaemia

• Older males
• IgM paraprotein
• Hyperviscosity syndrome
• Lymphadenopathy
• Malaise and weight loss

Complications of hyperviscosity syndrome

• Headaches
• Visual disturbance - retinal artery and vein occlusion
• Cerebrovascular accidents - indication for urgent plasmapheresis
• Thrombophilia