Senior Academic Half Day: Malignant Haematology Beth Harrison Department of Haematology University Hospitals Coventry and Warwickshire NHS Trust

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

Case 1 Hb 8.6 WCC 1.2 Platelets 12 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 Hb 8.6 WCC 1.2 Platelets 12 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?

Blasts in bone marrow (+blood) Molecular diagnostics Case 1 + 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

Case 4 Treatment: Chemotherapy Radiotherapy Risks of treatment: Breast cancer Thyroid cancer Secondary leukaemia / myelodysplasia Infertility Other endocrine failure - early menopause Bones Cardiac damage (chemo + radiotherapy) Risks of treatment?

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