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Senior Academic Half Day:Malignant Haematology
Beth Harrison
Department of Haematology
University Hospitals Coventry and Warwickshire NHS Trust
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• Normal haematopoiesis
• Investigations in malignant haematology
• Approach to a patient with pancytopenia
• Diagnosis and management
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Case 1
• 35 year old male
• 6 weeks recurrent throat infections
• 2 weeks easy bruising
• Hb 8.6
• WCC 1.2
• Platelets 12
Pancytopenia – he will need a bone marrow examination
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Bone Marrow Examination
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Normal Bone Marrow Aspirate
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Normal bone marrow trephine
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Case 1
• 35 year old male
• 6 weeks recurrent throat infections
• 2 weeks easy bruising
• Hb 8.6
• WCC 1.2
• Platelets 12
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• Hb 8.6
• WCC 1.2 +• Platelets 12
=Acute Leukaemia
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What is acute leukaemia?
What is a “blast”?
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Case 1
+
+
Diagnosis = Acute myeloid leukaemia
Bone marrow failure
Blasts in bone marrow (+blood)
Molecular diagnostics
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Case 1
• The Patient receives some chemotherapy
• Presents to A&E
• Pyrexial
• Shivery, vomiting, diarrhoea
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Neutropenic Sepsis
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Neutropenic Sepsis
• Treat as neutropenic without waiting for FBC result
• Blood cultures
• Broad spectrum antibiotics within 30 minutes of presentation
• IV fluid resuscitation
• Get help
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Fungal Pneumonia – Probably Aspergillus
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Management of acute leukaemia
• Chemotherapy• BUT:
– Filtered air
– No plants or flowers
– No unnecessary visitors
– Washed food – no salad or grapes or black pepper
– Antifungal prophylaxis
– Mouthcare
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Indications for bone marrow • Diagnostic
– Abnormal FBC– Investigation of paraproteinaemia– Bone lesions in pelvis accessible by this route– Pyrexia of unknown origin
• ? TB in HIV+ • ? foreign travel / splenomegaly
– Isolated splenomegaly with diagnosis unclear from PB
• Staging– Hodgkin Lymphoma / Non Hodgkin Lymphoma
• Treatment response– Leukaemia, Myeloma, Lymphoma etc
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Case 2
• 56 year old man
• back pain, vomiting and constipation
• Na 145 Calcium 3.25 K 5.7 Total protein 126 Urea 46 Albumin 34 Creat 565
• Hb 8.7
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Investigations:• Protein electrophoresis – of what?
• Bone marrow examination – for what?
• Skeletal survey – is what?
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Investigations:• Serum / urine
electrophoresis
• Bone marrow examination
• Skeletal survey
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What is the diagnosis?
• Multiple myeloma
• First management issues?
• Correct calcium
• Give fluids
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Renal Failure in Myeloma
• Light chain deposition in kidney
• Hypercalcaemia
• Hyperuricaemia
• Dehydration
• Non-steroidal anti-inflammatories• Plasma cell infiltration of kidney
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Urine free light chains: An old story
Previous polyclonal antisera against light chains could not distinguish light chains bound into whole immunoglobulin molecules from free light chains
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Case 3
• 35 year old woman with 2 years of lethargy and intermittent LUQ pain
• now complaining of dizziness
Visible white cells
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Case 3
• On examination:• Massive splenomegaly
Fundal haemorrhages• Diagnosis• Chronic myeloid leukaemia with
hyperviscosity resulting from WCC
• Immediate management• Get the white cell count down!!
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Myeloproliferative Disorders
• Clonal, pre-leukaemic• Uncontrolled proliferation of one or more
bone marrow lineages:– Red cells – primary polycythaemia– Platelets – essential thrombocythaemia– White cells (myeloid) – chronic myeloid
leukaemia– Fibroblasts - myelofibrosis
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Myeloproliferative Disorders
• Primary Polycythaemia and Essential Thrombocythaemia:– Increased vascular events– Treatment is aimed at reducing these
Hb>19?
Plts>700?
Ask!
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Causes of hyperviscosity
• Paraprotein (IgM > IgA > IgG)
• High WCC (CML / AML > CLL)
• High red cell mass (polycythaemia)
• Raised platelet count – (>1,000, myeloproliferative rather than
reactive)
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Causes of splenomegaly• Haematological
– Chronic myeloid leukaemia, Myelofibrosis– Chronic lymphatic leukaemia– Acute lymphoblastic leukaemia– Lymphoma (various)
• Infective – EBV– Chronic malaria– Visceral Leishmaniasis
• Liver Other– HCV / HBV with portal hypertension– Any cause cirrhosis with portal hypertension
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Case 4
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Indications for lymph node biopsy
• Generalised lymphadenopathy, FBC unhelpful. – (Also palpable cervical LN with mediastinal LN on CXR)
• Isolated lymphadenopathy – no obvious pathology in the anatomical region drained – (ENT: nasendoscopy NAD, FNA unhelpful)
• Regional lymphadenopathy with obvious primary pathology inaccessible to biopsy
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Findings on lymph node biopsy?
• Reactive
• Necrotic
• Granulomatous – TB, Sarcoid?
• HIV?
• Metastatic Carcinoma
• Metastatic Melanoma
• Lymphoma
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Non-Hodgkin’s Lymphoma: T cell
Hodgkin Lymphoma
Non-Hodgkin’s Lymphoma: B cell
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Case 4
• Nodular Sclerosing Hodgkin Lymphoma
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Risks of treatment?
Case 4
• Risks of treatment:– Breast cancer– Thyroid cancer– Secondary leukaemia / myelodysplasia– Infertility– Other endocrine failure - early menopause– Bones– Cardiac damage (chemo + radiotherapy)
Treatment:
Chemotherapy
Radiotherapy
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Intraabdominal lymphoma
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PET-CT in staging lymphoma
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PET-CT in staging lymphoma
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Indolent Non-Hodgkin Lymphoma: localised to one site
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Aggressive Non-Hodgkin Lymphoma
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Thank you