Aims and objectives Why is haematology so difficult? • Classification of malignancies • Haematology is a specialist area • Only learn what you need to know for exams • Duration: 70 mins • Slides and recordings: app.bitemedicine.com • 2
Case-based discussion: 1 History and examination A 55-year-old male presents with a 3-week history of tiredness and weight loss. On examination, you note bruising on his legs and hepatosplenomegaly. Observations (1) HR 80, BP 118/77, RR 18, SpO2 98%, Temp 37.0 3
Question 1 A 45-year-old male presents with a 3-week history of tiredness and weight loss. On examination, you note bruising on his legs and hepatosplenomegaly. Observations: HR 80, BP 118/77, RR 18, SpO2 98%, Temp 37.0 Q1 Q2 Which of the following is the most likely diagnosis? Acute myeloid leukaemia Chronic myeloid leukaemia Acute lymphoblastic leukaemia Chronic lymphocytic leukaemia Hodgkin lymphoma app.bitemedicine.com 4
Explanations Q1 Q2 Which of the following is the most likely diagnosis? Acute myeloid leukaemia Most common acute leukaemia in adults and can present with gum infiltration Chronic myeloid leukaemia Seen in older patients and does not show gum infiltration Acute lymphoblastic leukaemia Usually seen in children Chronic lymphocytic leukaemia Usually seen in elderly Hodgkin lymphoma No evidence of lymphadenopathy app.bitemedicine.com 5
Case-based discussion: 1 History and examination A 45-year-old male presents with a 3-week history of tiredness and weight loss. On examination, you note bruising on his legs and hepatosplenomegaly. Observations (1) HR 80, BP 118/77, RR 18, SpO2 98%, Temp 37.0 6
Introduction: Haematopoiesis (2) 7
(3) 8
Introduction: Malignancy 9
Clinical features: General principles Symptoms/Signs Bone marrow failure Anaemia • Fatigue • Pallor Thrombocytopaenia • Bleeding: bruising and epistaxis Dysfunctional white cells • Recurrent infections Constitutional symptoms Weight loss Fatigue Fever Loss of appetite Infiltration Hepatosplenomegaly Lymphadenopathy Gum hyperplasia (AML) 10
Investigations: General principles Bedside Full set of observations • Bloods FBC • Blood film • Clotting screen • Imaging CT imaging • Special tests Bone marrow aspirate and biopsy • Lymph node biopsy • Immunophenotype • Genetic testing • 11
Introduction: Acute myeloid leukaemia Myeloid Definition: proliferation of immature myeloid cells Immature = acute leukaemia • AML Mature = chronic leukaemia • CML Epidemiology: Myelofibrosis Most common acute leukaemia in adults • Polycythaemia vera 3000 cases per year in the UK (cancer research UK) • Essential thrombocytosis Risk factors Age: average age of diagnosis is 68 years old • Myelodysplasia: precursor lesion and evolves to AML in 30% of • cases Chemotherapy • Radiotherapy •
Question 2 A 45-year-old male presents with a 3-week history of tiredness and weight loss. On examination, you note bruising on his legs and hepatosplenomegaly. Observations: HR 80, BP 118/77, RR 18, SpO2 98%, Temp 37.0 Q1 Q2 Which of the following translocations is associated with AML? t(9;22) t(8;14) t(12;21) t(15;17) t(14;18) app.bitemedicine.com 13
Explanations Q1 Q2 Which of the following translocations is associated with AML? t(9;22) Associated with CML. ~2% of AML patients may have the translocation, however t(8;14) Associated with Burkitt’s lymphoma t(12;21) Associated with ALL t(15;17) Associated with AML (subtype acute promyelocytic leukaemia) t(14;18) Associated with follicular lymphoma app.bitemedicine.com 14
Pathophysiology: Acute myeloid leukaemia 9 subtypes of AML (FAB classification) Acute promyelocytic leukaemia (M3) t(15;17): fusion of retinoic acid receptor with • promyelocytic protein which blocks maturation Younger patients ~ 45 years old • Associated with disseminated intravascular • coagulation Good prognosis • Acute monocytic leukaemia (M5) Monoblast accumulation • Gum infiltration • (4)
Pathophysiology: Acute myeloid leukaemia Myelodysplasia (NOT MYELOFIBROSIS!) Neoplastic proliferation of immature myeloid cells • with evidence of dysplasia Pre-cursor lesion to AML • 30% of cases progress to AML • Blast cells on marrow <20% • (4)
Investigations & Management: Acute myeloid leukaemia Investigations FBC: leukocytosis, thrombocytopaenia, anaemia • Blast cells crowd out bone marrow causing low PLTs and Hb • Blood film: immature myeloid cells with auer rods • Clotting screen: deranged in disseminated intravascular coagulation • Bone marrow biopsy: ≥20% myeloblasts is diagnostic • Cytogenetic studies: t(15;17) • Management Induction • APML: all-trans retinoic acid • Consolidation •
Investigations & Management: Acute myeloid leukaemia Auer rods: aggregates of myeloperoxidase Seen in immature myeloid • cells (5)
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Introduction: Chronic myeloid leukaemia Myeloid Definition: myeloproliferative condition. Neoplastic proliferation of mature myeloid cells (granulocytes and their precursors) AML Immature = acute leukaemia • Mature = chronic leukaemia • CML Myelofibrosis Risk factors Age: 65-75 years of age • Polycythaemia vera Radiation • Essential thrombocytosis
Q1 Question 3 Once CML is confirmed, which of the following is first-line management? All-trans retinoic acid Imatinib Stem cell transplant IFN alpha Hydroxyurea app.bitemedicine.com 21
Explanations Q1 Once CML is confirmed, which of the following is first-line management? All-trans retinoic acid Treatment for APML Imatinib Tyrosine kinase inhibitor blocks BCR ABL protein Stem cell transplant May be used in refractory disease in those who are fit enough IFN alpha Can be used, but typically in combination with a tyrosine kinase inhibitor Hydroxyurea May be given but Imatinib is the first line therapy app.bitemedicine.com 22
Pathophysiology: Chronic myeloid leukaemia Tyrosine kinase activity Constitutive activity • (4) (6)
Investigations & Management: Chronic myeloid leukaemia Investigations FBC: leukocytosis, thrombocytosis or thrombocytopaenia, anaemia • Raised granulocyte count • Blood film: increased number of mature granulocytes (<10% blast cells) • Bone marrow biopsy: increased number of mature granulocytes • Myeloblasts not prevalent • Cytogenetic studies: Philadelphia chromosome t(9;22) • Leukaemia Prevalence of Management Philadelphia chromosome Tyrosine kinase inhibitor • CML • 95% Inhibits BCR-ABL fusion product • AML • 2% ALL • 5% children • 20% adults
Investigations & Management: Chronic myeloid leukaemia (7)
Complications: Chronic myeloid leukaemia Chronic phase Accelerated phase Blast transformation Summary Indolent and lasts many Progression of disease Transformation to acute years leukaemia with poor prognosis rd AML • 2/3 rd ALL • 1/3 Cell counts in blood <10% blast cells <20% blast cells ≥20% blast cells
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Introduction: Myelofibrosis Myeloid Definition: myeloproliferative condition. Neoplastic proliferation of mature myeloid cells, particularly megakaryocytes AML Leading to marrow fibrosis • CML Myelofibrosis Risk factors Age: >65 years • Polycythaemia vera Radiation • Essential thrombocytosis
Pathophysiology: Myelofibrosis (4)
Q1 Question 4 Which of the following is associated with myelofibrosis? Hypercellular bone marrow Lymphoblasts Smudge cell Teardrop red cell ‘Wet tap’ app.bitemedicine.com 30
Explanations Q1 Which of the following is associated with myelofibrosis? Hypercellular bone marrow Marrow fibrosis, not hypercellular Lymphoblasts Myeloid, not a lymphoid condition Smudge cell Ruptured leucocytes seen in CLL Teardrop red cell Seen on blood film in myelofibrosis ‘Wet tap’ Marrow fibrosis means aspiration is not possible → ‘dry tap’ app.bitemedicine.com 31
Investigations & Management: Myelofibrosis Investigations FBC: anaemia, other cell counts may be low or variable • Blood film: leucoerythroblastic smear • Tear drop RBCs, nucleated RBCs, immature granulocytes • Bone marrow aspirate: ‘dry - tap’ • Bone marrow biopsy: marrow fibrosis • Genetics: JAK2 V617F mutation in 50-60% of patients • Management Chemotherapy •
Investigations & Management: Myelofibrosis (8)
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Introduction: Polycythaemia vera Myeloid Definition: myeloproliferative disorder. Neoplastic proliferation of mature myeloid cells, particularly RBCs AML Can also have thrombocytosis and granulocytosis • CML Risk factors Myelofibrosis Age: peak incidence 50-70 years of age • Male • Polycythaemia vera Essential thrombocytosis
Pathophysiology: Polycythaemia vera JAK2 V617F mutation (4)
Clinical features Clinical features related to hyperviscosity PCV Headache Blurry vision Flushed appearance Palmar erythema Itching after a bath (release of histamine) Erythromelalgia • Burning pain of extremities Increased risk of thrombosis 37
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