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6. Cancer > Leukaemias > Flashcards

Leukaemias Flashcards

1
Q

What is haematopoiesis?

A

The formation of blood cellular components, which are all derived from haematopoietic stem cells

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2
Q

What are the two main progenitor cells in haematopoiesis?

A

Common myeloid progenitor

Common lymphoid progenitor

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3
Q

What cells do myeloid progenitors give rise to?

A

Erythrocytes
Mast cells
Myoblasts

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4
Q

What cells do lymphoid progenitors give rise to?

A

Natural killer cells
T lymphocytes
B lymphocytes (and thus plasma cells)

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5
Q

What cells do myoblasts give rise to?

A

Basophil
Neutrophil
Eosinophil
Macrophages

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6
Q

From what progenitor has a myoblast differentiated?

A

Common myeloid progenitor

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7
Q

Where does haematopoiesis take place in adults?

A

The areas producing blood cells are the pelvis, spine, ribs, cranium, and proximal ends of long bones (bone marrow)

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8
Q

How are haematological neoplasms categorised?

A

Historically, hematological malignancies have been most commonly divided by whether the malignancy is mainly located in the blood (leukemia) or in lymph nodes (lymphomas).

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9
Q

What are characteristic features of acute haematological neoplasms?

A

Predominantly immature cells

Rapidly progressive and aggressive; fatal within days to week

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10
Q

What are characteristic features of chronic haematological neoplasms?

A

Predominantly mature cells

Indolent and slowly progressive; patients can live with the disease for a long period of time

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11
Q

What is myeloma?

A

Malignant disease of plasma cells

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12
Q

What are the four main leukaemias?

A
  1. Acute myeloid leukaemia
  2. Acute lymphoblastic leukaemia
  3. Chronic myeloid leukaemia
  4. Chronic lymphocytic leukaemia
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13
Q

What is the most common age group for acute lymphoblastic leukaemia?

A

Childhood (2-5 years)

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14
Q

What is the most common age group for chronic lymphocytic leukaemia?

A

Elderly

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15
Q

How is leukaemia diagnosed?

A

Leukaemia can be diagnosed by examination of a stained slide of peripheral blood and bone marrow, but immunophenotyping, cytogenetics and molecular genetics are essential for complete subclassification and prognostication

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16
Q

How would you investigate the degree of maturity of the leukaemic clone?

A

Expression of cytosolic enzymes and expression of surface antigens

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17
Q

What is the cause of acute leukaemia?

A
  1. Genetic syndromes
  2. Environmental risk factors
    - Radiation
    - Prior chemotherapy
    - Prior infections
    - drugs (benzene)
  3. KMT2A mutation
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18
Q

From what cell does acute lymphoblastic leukaemia develop?

A

Lymphoid blast

ALL emerges when a single lymphoblast gains many mutations to genes that affect blood cell development and proliferation

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19
Q

What characteristic genetic changes need to have to increase the chance of developing leukemia?

A

Chromosomal translocations, intrachromosomal rearrangements, changes in the number of chromosomes in leukemic cells, and additional mutations in individual genes

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20
Q

How is C-Myc implied in leukemia?

A

“An example of this includes the translocation of C-MYC, a gene that encodes a transcription factor that leads to increased cell division, next to the immunoglobulin heavy- or light-chain gene enhancers, leading to increased C-MYC expression and increased cell division”

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21
Q

What does immunohistochemical testing in acute lymphoblastic leukaemia reveal?

A

TdT or CALLA antigens on the surface of leukaemic cells

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22
Q

Where do leukemias often metastasise to?

A

Lung, liver, spleen, lymph nodes, brain, kidneys, and reproductive organs

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23
Q

What is a histological marker for the myeloid lineage?

A

myeloperoxidase (MPO)

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24
Q

What genetic diseases are associated with leukaemias?

A

Fanconi anaemia, ataxia telangiectasia and Li–Fraumeni syndrome

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25
Q

What is the median age of onset for acute myeloid leukaemia?

A

65

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26
Q

What would blood tests for acute leukaemias show?

A
  1. Blood count –> Hb low, WBC raised, platelets low
  2. Blast cells seen
  3. Bone marrow aspirate -> increased cellularity, reduced erythropoiesis, reduced megakaryocytes (replaced by blast cells)
  4. Chest X-ray. Mediastinal widening often present in T lymphoblastic leukaemia
  5. Cerebrospinal fluid examination. Performed in all patients with ALL, as the risk of CNS involvement is high. It is less critical in AML
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27
Q

What are the respective lineages established by immunophenotyping for the different types of acute leukaemias?

A

AML – CD33 or CD13, B lineage

ALL – CD10 and
CD19 and T lineage – CD3

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28
Q

How would you manage acute lymphoblastic leukaemia?

A

First line: Pegaspargase (chemotherapy)

In complete remission with minimal residual disease: Blinatumomab

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29
Q

What is a blast cell?

A

An immature precursor of myeloid cells (myeloblasts) or lymphoid cells (lymphoblast)

Rarely ever seen in normal individuals

If present, are highly suggestive of an acute leukaemia

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30
Q

How would you manage a relapsed acute lymphoblastic leukaemia?

A

Tisagenlecleucel

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31
Q

How is the Philadelphia chromosome implicated in cancer?

A

The Philadelphia chromosome is a cytogenetic anomaly that is manifested as a shortened version of human chromosomes 9 and 22.

Ph chromosomes are present in over 90% of chronic myelogenous leukemia (CML) patients and also in 25% of adult acute lymphocytic leukemia (ALL) patients.

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32
Q

How is the Philadelphia chromosome implicated in chronic myelogenous leukemia specifically?

A

Associated with 97% of cases

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33
Q

What, on a molecular level, does the Philadelphia chromosome do?

A

The molecular consequences of the translocation are that part of the Abelson proto-oncogene (c-ABL) normally present on chromosome 9 is translocated to chromosome 22, where it comes into juxtaposition with a region of chromosome 22 named the ‘breakpoint cluster region, it is is now a fused BCR-ABL protein which acts as a tyrosine kinase

BCR-ABL activates a cascade of proteins that control the cell cycle and inhibits DNA repair

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34
Q

What is the prognosis for acute lymphoblastic leukaemia?

A

Children: 90% five-year survival rate

Adults: 35% five-year survival

35
Q

What is acute myeloid leukemia?

A

A cancer of the myeloid line of blood cells, characterised by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production

36
Q

What chemicals can predispose someone to acute myeloid leukemia?

A

AML occurs after treatment with alkylating agents and topoisomerase II inhibitors

37
Q

What tissues may acute myeloid leukemia infiltrate?

A

Brain
Skin
Gums (can swell)

38
Q

What are the pathological processes that give rise to leukaemia signs and symptoms?

A
  1. Marrow failure (anaemia, neutropenia, thrombocytopenia)
  2. High WBC
  3. Tissue infiltration (marrow, gums, skin, liver and spleen, nodes, CNS)
  4. Substance release
39
Q

What symptoms does marrow failure lead to?

A 
Breathlessness
Fatigue
Angina
Claudication
Infections
Bleeding and bruising
40
Q

What symptoms does a high white blood cell count lead to?

A

Confusion
Visual problems
Headache
COnfusion

41
Q

What symptoms does tissue infiltration lead to?

A

Bone pain

Headaches

42
Q

What symptoms does substance release lead to?

A

Bleeding and bruising
Acute gout
Tumour lysis

43
Q

What are Auer rods?

A

Auer rods are large, crystalline cytoplasmic inclusion bodies

Highly diagnostic of acute myeloid leukaemia

44
Q

What is the management for acute myeloid leukaemia?

A

Chemotherapy

45
Q

What is most common acute leukaemia?

A

acute myeloid leukaemia

46
Q

What is the most common age group for chronic myeloid leukaemia?

A

40-60

47
Q

What is a cytogenetic hallmark of chronic myeloid leukaemia?

A

Presence of Philadelphia chromosome

JAK2 mutation

48
Q

What is the difference between acute and chronic myeloid leukaemia?

A

CML has a more slowly progressive course, which if not initially cured, will be followed eventually by ‘blast crisis’ transformation to acute leukaemia

49
Q

What are the symptoms of chronic myeloid leukaemia?

A

Symptomatic anaemia (e.g. shortness of breath) Abdominal discomfort due to splenomegaly
Weight loss
Fever, sweats, in the absence of infection
Headache (occasionally) or priapism due to hyperleucocytosis
Bruising, bleeding (uncommon)

50
Q

What are the signs of chronic myeloid leukaemia?

A

Pallor
Splenomegaly, often massive
Lymphadenopathy (uncommon, suggests blast crisis)
Extramedullary soft tissue leukaemic deposit ‘chloroma’
(= blast crisis)
Retinal haemorrhage due to leucostasis.

51
Q

How are myeloproliferative neoplasms defined?

A

Myeloproliferative neoplasms (MPNs) are a group of rare blood cancers in which excess red blood cells, white blood cells or platelets are produced in the bone marrow.

52
Q

What cells are excessively produced and unregulated in chronic myeloid leukaemia?

A

CML is a clonal bone marrow stem cell disorder in which a proliferation of mature granulocytes (neutrophils, eosinophils and basophils)

53
Q

What is the main risk factor for chronic myeloid leukaemia?

A

Radiation exposure

54
Q

What would investigations for chronic myeloid leukaemia show?

A
  1. Blood count → Hb low/normal, WBC raised, platelets low/normal/raised
  2. Blood film → Neutrophilia with the whole spectrum of mature myeloid precursors. Elevated basophils and eosinophils
  3. Bone marrow aspirate → Increased cellularity, increased myeloid precursors. Ph chromosome
  4. FISH → cytogenetic/molecular abnormality
55
Q

How would you manage chronic myeloid leukaemia?

A

Imatinib, a tyrosine kinase inhibitor that specifically blocks the enzy- matic action of the BCR-ABL fusion protein, which is now first-line treatment for the chronic phase

Allogeneic haemopoietic stem cell transplantation can cure approximately 70% of chronic phase CML patients. It is now used in those with an inadequate response to imatinib or those that have disease progression on therapy.

56
Q

What is the response rate in chronic myeloid leukaemia treated with imatinib?

A

Imatinib produces a complete haematological response in over 95% of patients and 70–80% of these have no cytogenetically detectable BCR-ABL translocation in the marrow

57
Q

What is a blast crisis?

A

Blast crisis is the final phase in the evolution of CML, and behaves like an acute leukemia, with rapid progression and short survival

Blast crisis is diagnosed if any of the following are present in a patient with CML:

  1. > 20% blasts in the blood or bone marrow
  2. The presence of an extramedullary proliferation of blasts

Patients in blast phase often have a fever, an enlarged spleen, weight loss, and generally feel unwell.

58
Q

What is the most common chronic leukaemia?

A

Chronic lymphocytic leukemia

59
Q

What is the median age of onset for chronic lymphocytic leukemia?

A

65-67

60
Q

What is the clinical presentation of chronic lymphocytic leukemia?

A

The majority of patients are asymptomatic, identified as a chance finding on a blood count performed for another indication.

Other patients, however, present with the features of marrow failure or immunosuppression

61
Q

What is the median survival for chronic lymphocytic leukemia?

A

The median survival is about 10 years and prognosis correlates with clinical stage at presentation

62
Q

How is chronic lymphocytic leukemia defined?

A

A type of cancer in which the bone marrow makes too many lymphocytes

63
Q

In the later stages of the disease, what are the clinical features of lymphocytic leukemia?

A

Recurrent infection (fever)
Anaemia
Painless lymphadenopathy
Left upper quadrant discomfort (from splenomegaly).

64
Q

What would investigations for chronic lymphocytic leukaemia show?

A
  1. Blood count → Hb low/normal, WBC raised and may be very high, platelets low/normal
  2. Blood film → mall or medium-sized mature and normal-appearing lymphocytes, no immature blasts
  3. Bone marrow aspirate → Reflects peripheral blood, often very heavily infiltrated with lymphocytes.
  4. Immunophenotyping → mainly CD19+, CD5+, CD23+ B cells
65
Q

How high is the WBC count in chronic lymphocytic leukaemia?

A

criteria for diagnosis >5 × 10^9/L

66
Q

What are risk factors for chronic lymphocytic leukaemia?

A

Family history
Sun exposure
Insecticides
Exposure to Hep C

67
Q

What is the haematological, pathological finding in chronic lymphocytic leukaemia?

A

CLL results in the buildup of B cell lymphocytes in the bone marrow, lymph nodes, and blood.

These cells do not function well and crowd out healthy blood cells

68
Q

What genetic abnormalities can be seen in chronic lymphocytic leukaemia?

A

13q deletion
11q deletion or 17p deletion (the sites of the tumour suppressor genes ATM and TP53, respectively)
IgVH

69
Q

Depending on the genetic mutation in chronic lymphocytic leukaemia, how does the prognosis change?

A

13q deletion → excellent prognosis
11q deletion or 17p deletion → rapidly evolving clinical course
IgVH

70
Q

What cells are abundant in chronic lymphocytic leukaemia?

A

CD19+, CD5+, CD23+ B cells

71
Q

What type of cancer would insane lymphocytosis make you suspect?

A

chronic lymphocytic leukaemia

72
Q

What staging symptoms are used for chronic lymphocytic leukaemia?

A

Rai

Binet

73
Q

How would you manage chronic lymphocytic leukaemia?

A

In CLL, the major consideration is when to treat, indeed 30% of patients will never require intervention

Tyrosine Kinase Inhibitor: Imatonib

74
Q

What is tumour lysis syndrome?

A

Tumor lysis syndrome is a group of metabolic abnormalities that can occur as a complication during the treatment of cancer, where large amounts of tumor cells are lysed at the same time by the treatment, releasing their contents into the bloodstream

75
Q

Treatment for which cancers yields the highest risk for tumour lysis syndrome?

A

Lymphomas and leukaemias

76
Q

What is tumour lysis syndrome characterised by?

A 
Hyperrkalaemia
Hyperphosphatemia
Hypocalcemia
Hyperuricemia
Acute uric acid nephropathy

Leads to acute kidney failure

77
Q

What are risk factors for tumour lysis syndrome?

A

Tumours with a high cell turnover rate, rapid growth rate, and high tumor bulk

Chemo-sensitive tumors, such as lymphomas

78
Q

When would you suspect tumour lysis syndrome?

A

TLS should be suspected in patients with large tumor burden who develop acute kidney failure along with hyperuricemia (> 15 mg/dL) or hyperphosphatemia (>8 mg/dL)

Little to no urine output

79
Q

How would you manage tumour lysis syndrome?

A

FLUIDS

Oral or IV allopurinol (prevents acid buildup) or rasburicase (clears acid buildup)

80
Q

What are the different types of CML depending on the cells affected?

A
  1. Essential thrombocytaemia
  2. Polycythaemia vera
  3. Myelofibrosis

Caused by JAK2 mutation

81
Q

What symptoms do essential thrombocytaemia and polycythaemia vera lead to?

A
  1. Any clotting emergency (DVT, PE, etc)
  2. Lethargy
  3. Dizziness
  4. Tingling, tinnitus and itching
  5. Headaches and palpitations

In PV specifically: erythromyalgia

82
Q

What would a full blood count in acute leukaemias reveal?

A

WBC > 100
Hb < 10
Platelets < 30

Loads of blast cells, which will settle in the lungs and kidneys and cause AKI and consolidation/pneumonia

83
Q

What are the stages for AML as described by The French-American-British (FAB) classification of AML?

A

M0 → Undifferentiated acute myeloblastic leukemia
M1 → Acute myeloblastic leukemia with minimal maturation
M2 → Acute myeloblastic leukemia with maturation
M3 → Acute promyelocytic leukemia (APL)
M4 → Acute myelomonocytic leukemia
M5 → Acute monocytic leukemia
M6 → Acute erythroid leukemia
M7 → Acute megakaryoblastic leukemia

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