Senior Academic Half Day:Malignant Haematology

Beth HarrisonDepartment of HaematologyUniversity Hospitals Coventry and Warwickshire NHS Trust

• Normal haematopoiesis• Investigations in malignant haematology• Approach to a patient with pancytopenia• Diagnosis and management

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

Bone Marrow Examination

Normal Bone Marrow Aspirate

Normal bone marrow trephine

                       

                        

Case 1

• 35 year old male• 6 weeks recurrent throat infections• 2 weeks easy bruising• Hb 8.6• WCC 1.2• Platelets 12

• Hb 8.6

• WCC 1.2 +• Platelets 12

=Acute Leukaemia

What is acute leukaemia?

What is a “blast”?

• What is a stem cell?

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Case 1

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Diagnosis = Acute myeloid leukaemia

Bone marrow failure

Blasts in bone marrow (+blood)

Molecular diagnostics

Case 1

• The Patient receives some chemotherapy• Presents to A&E• Pyrexial• Shivery, vomiting, diarrhoea

Neutropenic Sepsis

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

Fungal Pneumonia – Probably Aspergillus

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

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

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

Investigations:• Protein electrophoresis – of what?

• Bone marrow examination – for what?

• Skeletal survey – is what?

Investigations:• Serum / urine

electrophoresis

• Bone marrow examination

• Skeletal survey

What is the diagnosis?

• Multiple myeloma

• First management issues?

• Correct calcium• Give fluids

Renal Failure in Myeloma

• Light chain deposition in kidney• Hypercalcaemia• Hyperuricaemia

• Dehydration• Non-steroidal anti-inflammatories• Plasma cell infiltration of kidney

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

Case 3

• 35 year old woman with 2 years of lethargy and intermittent LUQ pain

• now complaining of dizziness

Visible white cells

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!!

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

Myeloproliferative Disorders

• Primary Polycythaemia and Essential Thrombocythaemia:– Increased vascular events– Treatment is aimed at reducing these

Hb>19?

Plts>700?

Ask!

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)

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

Case 4

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

Findings on lymph node biopsy?

• Reactive• Necrotic • Granulomatous – TB, Sarcoid?• HIV?• Metastatic Carcinoma• Metastatic Melanoma• Lymphoma

Non-Hodgkin’s Lymphoma: T cell

Hodgkin Lymphoma

Non-Hodgkin’s Lymphoma: B cell

Case 4

• Nodular Sclerosing Hodgkin Lymphoma

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

Intraabdominal lymphoma

PET-CT in staging lymphoma

PET-CT in staging lymphoma

Indolent Non-Hodgkin Lymphoma: localised to one site

Aggressive Non-Hodgkin Lymphoma

Thank you