Aims and objectives Why is haematology so difficult? - - PowerPoint PPT Presentation

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Aims and objectives Why is haematology so difficult? - - PowerPoint PPT Presentation

Mar 17, 2023 175 likes •695 views

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:

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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
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History and examination

A 55-year-old male presents with a 3-week history

  • f 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

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Case-based discussion: 1

(1)

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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 Which of the following is the most likely diagnosis?

Question 1

Acute myeloid leukaemia Chronic myeloid leukaemia Acute lymphoblastic leukaemia Chronic lymphocytic leukaemia Hodgkin lymphoma app.bitemedicine.com

Q1 Q2

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Explanations

app.bitemedicine.com 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

Q1 Q2

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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

HR 80, BP 118/77, RR 18, SpO2 98%, Temp 37.0

6

Case-based discussion: 1

(1)

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Introduction: Haematopoiesis

(2)

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8 (3)

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Introduction: Malignancy

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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)

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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
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Introduction: Acute myeloid leukaemia

Definition: proliferation of immature myeloid cells

  • Immature = acute leukaemia
  • Mature = chronic leukaemia

Epidemiology:

  • Most common acute leukaemia in adults
  • 3000 cases per year in the UK (cancer research UK)

Risk factors

  • Age: average age of diagnosis is 68 years old
  • Myelodysplasia: precursor lesion and evolves to AML in 30% of

cases

  • Chemotherapy
  • Radiotherapy

Myeloid AML CML Myelofibrosis Polycythaemia vera Essential thrombocytosis

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Which of the following translocations is associated with AML?

Question 2

t(9;22) t(8;14) t(12;21) t(15;17) t(14;18) app.bitemedicine.com

Q2 Q1

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

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Explanations

app.bitemedicine.com 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

Q2 Q1

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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)

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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)

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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
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Investigations & Management: Acute myeloid leukaemia

Auer rods: aggregates of myeloperoxidase

  • Seen in immature myeloid

cells

(5)

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Introduction: Chronic myeloid leukaemia

Definition: myeloproliferative condition. Neoplastic proliferation of

mature myeloid cells (granulocytes and their precursors)

  • Immature = acute leukaemia
  • Mature = chronic leukaemia

Risk factors

  • Age: 65-75 years of age
  • Radiation

Myeloid AML CML Myelofibrosis Polycythaemia vera Essential thrombocytosis

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Once CML is confirmed, which of the following is first-line management?

Question 3

All-trans retinoic acid Imatinib Stem cell transplant IFN alpha Hydroxyurea app.bitemedicine.com

Q1

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Explanations

app.bitemedicine.com 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

Q1

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Pathophysiology: Chronic myeloid leukaemia

Tyrosine kinase activity

  • Constitutive activity

(4) (6)

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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)

Management

  • Tyrosine kinase inhibitor
  • Inhibits BCR-ABL fusion product

Leukaemia Prevalence of Philadelphia chromosome CML

  • 95%

AML

  • 2%

ALL

  • 5% children
  • 20% adults
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Investigations & Management: Chronic myeloid leukaemia

(7)

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Complications: Chronic myeloid leukaemia

Chronic phase Accelerated phase Blast transformation Summary Indolent and lasts many years Progression of disease Transformation to acute leukaemia with poor prognosis

  • 2/3

rd AML

  • 1/3

rd ALL

Cell counts in blood <10% blast cells <20% blast cells ≥20% blast cells

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Introduction: Myelofibrosis

Definition: myeloproliferative condition. Neoplastic proliferation of

mature myeloid cells, particularly megakaryocytes

  • Leading to marrow fibrosis

Risk factors

  • Age: >65 years
  • Radiation

Myeloid AML CML Myelofibrosis Polycythaemia vera Essential thrombocytosis

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Pathophysiology: Myelofibrosis

(4)

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Which of the following is associated with myelofibrosis?

Question 4

Hypercellular bone marrow Smudge cell Teardrop red cell ‘Wet tap’ app.bitemedicine.com

Q1

Lymphoblasts

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Explanations

app.bitemedicine.com 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’

Q1

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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
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Investigations & Management: Myelofibrosis

(8)

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Introduction: Polycythaemia vera

Definition: myeloproliferative disorder. Neoplastic proliferation of

mature myeloid cells, particularly RBCs

  • Can also have thrombocytosis and granulocytosis

Risk factors

  • Age: peak incidence 50-70 years of age
  • Male

Myeloid AML CML Myelofibrosis Polycythaemia vera Essential thrombocytosis

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Pathophysiology: Polycythaemia vera

JAK2 V617F mutation

(4)

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Clinical features

PCV

Headache Blurry vision Flushed appearance Palmar erythema Itching after a bath (release of histamine) Erythromelalgia

  • Burning pain of extremities

Increased risk of thrombosis Clinical features related to hyperviscosity

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In a patient with polycythaemia vera, which of the following should be started?

Question 5

Aspirin Hydroxycarbamide (hydroxyurea) Imatinib Phenoxymethylpenicillin app.bitemedicine.com

Q1

Warfarin

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Explanations

app.bitemedicine.com In a patient with polycythaemia vera, which of the following should be started? Aspirin Patients should be started on an antiplatelet Warfarin Antiplatelets, not anticoagulants, are used Hydroxycarbamide (hydroxyurea) May be used in high risk patients Imatinib Used in CML Phenoxymethylpenicillin Not indicated here

Q1

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Investigations & Management: Polycythaemia vera

Investigations

  • FBC: raised Hb and haematocrit
  • Granulocytes and PLTs may also be raised
  • EPO: low in polycythaemia vera
  • Raised in secondary polycythaemia e.g. hypoxia
  • Genetics: JAK2 V617F mutation in 95% of patients

Management

  • Phlebotomy: aim for haematocrit <45%
  • Aspirin
  • Hydroxyurea: in patients at high risk of thrombosis e.g. >60 years of age
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Introduction: Essential thrombocytosis

  • Definition: myeloproliferative disorder. Neoplastic proliferation
  • f mature myeloid cells, particularly megakaryocytes
  • Increased risk of bleeding and/or thrombosis

Risk factors

  • Age: >50-70 years of age

Myeloid AML CML Myelofibrosis Polycythaemia vera Essential thrombocytosis

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Pathophysiology: Essential thrombocytosis

JAK2 V617F mutation

(4)

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Investigations & Management: Essential thrombocytosis

Investigations

  • FBC: thrombocytosis (PLTs > 600,000)
  • Bone marrow biopsy: increased megakaryocytes
  • Genetics: JAK2 mutation in 50-60% of patients

Management

  • Antiplatelet e.g. aspirin
  • Hydroxycarbamide
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Recap

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Top-decile question

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Explanations

app.bitemedicine.com Which of the following is a poor prognostic factor in ALL? Age < 10 years Age > 10 years carries a poorer prognosis WCC 25 x 109/L WCC > 30 carries a poorer prognosis t(12;21) Good prognostic factor t(9;22) Poor prognostic factor >20% lymphoblasts on bone marrow biopsy This is needed for a diagnosis of ALL

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References

1. Herbert L. Fred, MD and Hendrik A. van Dijk / CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0) 2. A.Rad and Mikael Häggström, M.D. - Author info - Reusing imagesExample citation (in caption or footnote):- &quot;By A. Rad and M. Häggström. CC- BY-SA 3.0 license.&quot; / CC BY-SA (http://creativecommons.org/licenses/by-sa/3.0/) 3. ARad (creation of original), RexxS, Mikael Häggström and birdy and Mikael Häggström, M.D. - Author info - Reusing images / CC BY-SA (http://creativecommons.org/licenses/by-sa/3.0/) 4.

  • Modified. A.Rad and Mikael Häggström, M.D. - Author info - Reusing imagesExample citation (in caption or footnote):- &quot;By A. Rad and M.

Häggström. CC-BY-SA 3.0 license.&quot; / CC BY-SA (http://creativecommons.org/licenses/by-sa/3.0/) 5. Paulo Henrique Orlandi Mourao / CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0) 6. Aryn89 / CC BY-SA (https://creativecommons.org/licenses/by-sa/4.0) 7. J3D3 / CC BY-SA (https://creativecommons.org/licenses/by-sa/4.0) 8.

  • Prof. Osaro Erhabor / CC0

All other images were made by BiteMedicine or under basic license from Shutterstock and not suitable for redistribution.

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