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Immunology and Haematology > Haematological Malignancies > Flashcards

Haematological Malignancies Flashcards

1
Q

Describe pathogenesis of haematological malignancy

A

Multi step process

Acquired genetic alterations in a long lived cell

Proliferative/survival advantage to mutated cell

This produces malignant clone

Malignant clone grows to dominate tissue

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2
Q

Leukaemia v lymphoma

A

leukaemia bone marrow

lymphoma lymphoid tissue

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3
Q

Describe features of acute leukaemia

A

Leukamic cells do not differentiate

Bone marrow failure

Rapidly fatal if untreated

Potentially curable; childhood acute lymphoblastic leukaemia

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4
Q

Describe features of chronic leukaemia

A

Leukaemic cells retain ability to differentiate

Proliferation without bone marrow failure

Survival for a few years

Potentially curable with modern therapy; tyrosine kinase inhibitors in CML

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5
Q

What are the parts of a lymph node?

A

Medulla
Paracortex
Cortex
B cell follicle; germinal centre, mantle zone, marginal zone

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6
Q

What can cause localised, painful lymphadenopathy?

A

Bacterial infection in draining site

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7
Q

What can cause localised, painless lymphadenopathy?

A

Rare infections, catch scratch fever, TB

Metastatic carcinoma from draining site; hard

Lymphoma; rubbery

Reactive, no cause identified

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8
Q

What can cause generalised, painful/tender lymphadenopathy?

A

Viral infections, EBV, CMV, hepatitis, HIV

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9
Q

What can cause generalised, painless lymphadenopathy?

A

Lymphoma

Leukaemia

Connective tissue diseases, sarcoidosis

Reactive, no cause identified

Drugs

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10
Q

How can lymphoma present?

A

Nodal disease

  • > 90% HL present with nodal disease
  • ~60% NHL present with purely nodal disease

Extranodal disease

Systemic symptoms; fever, drenching sweats, wt loss, pruritis, fatugue

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11
Q

What are symptoms of acute lymphoblastic leukaemia?

A

Lymphadenopathy
Hepatosplenomegaly
Pallor, echymoses, petechiae
Neurological signs

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12
Q

Investigations for acute lymphoblastic leukaemia

A 
FBC
Peripheral blood smear
Serum electrolytes
Renal function
Liver function
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13
Q

Describe treatment of acute lymphoblastic leukaemia

A

Chemotherapy
Fluid therapy + allopurinol/rasburicase
Prophylactic antimicrobials

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14
Q

What is acute myeloid leukaemia?

A

Clonal expansion of bone marrow blasts in bone marrow, peripheral blood or extramedullary tissues

Bone marrow blasts of at least 20% are diagnostic

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15
Q

What are symptoms of acute myeloid leukaemia?

A 
Pallor
Fatigue
Ecchymoses or petechiae
Infection (due to neutropenia)
Palpitations
Dizziness
Dyspnoea
Infection or fever
Lymphadenopathy
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16
Q

What are investigations for acute myeloid leukaemia?

A 
FBC; WCC high but possible neutropenia
Peripheral blood smear
Coagulation pannel
Bone marrow aspirate
Cytogenics
Serum electrolytes
Renal function
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17
Q

What is the treatment for acute myeloid leukaemia?

A

Chemotherapy
Fluid + allopurinol/rasburicase

Allogenic stem cell transplantation

If unable to tolerate chemo then cytarabine

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18
Q

What are symptoms of chronic myeloid leukaemia?

A 
Splenomegaly
Left upper quadrant discomfort
Dyspnoea
Wt loss
Excess sweating
Pallor
Fever
Gout
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19
Q

Investigations for chronic myeloid leukaemia

A

FBC
Metabolic profile
Peripheral blood smear; mature or maturing myeloid cells, increased basophils
Bone marrow biopsy; granulocytic hyperplasia, hypercellular

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20
Q

Treatment of chronic myeloid leukaemia

A

First presentation; tyrosine kinase inhibitor (end in ‘inib’)

Progression after TKI therapy; allogeneic HSCT plus high dose chemo

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21
Q

Symptoms of chronic lymphocytic leukaemia

A 
Dyspnoea
Fatigue
Lymphadenopathy
Splenomegaly
Hepatomegaly
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22
Q

Investigations for chronic lymphocytic leukaemia

A 
WBC Count
Blood film; smudge cells
Haemoglobin; low
Platelet count; low
Flow cytometry; positive for dim surface Ig
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23
Q

Treatment of chronic lymphocytic leukaemia

A

Observation if early stage

Chemoimmunotherapy or ibrutinib

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24
Q

What is Rai staging?

A

Classification of CLL

0-IV

0 ; lymphocytosis but not other physical signs
I ; lymphocytosis and lymphadenopathy
II ; Lypmhocytosis, hepato/splenomegaly and might have lymphadenopathy
III ; lymphocytosis and anaemia. Maybe hepato/splenomegaly and lymphadenopathy
IV ; lymphocytosis and low platelets, all other signs possible

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25
Q

What are the cells in Hodgkin’s lymphoma?

A

Arises from mature B cells

Characterised by presence of Hodgkin’s cells and Reed-Steinberg cells

26
Q

What are the cells in Hodgkin’s lymphoma?

A

Arises from mature B cells

Characterised by presence of Hodgkin’s cells and Reed-Sternberg cells

27
Q

Investigations for Hodgkin’s lymphoma

A 
FBC
Metabolite panel
CXR
ESR
Lymph node biopsy
28
Q

Treatment of Hodgkin’s lymphoma

A

Chemotherapy + Radiotherapy in classical HL

Radiotherapy in early nodular lymphocyte-predominant HL
Chemotherapy in late nodular lymphocyte-predominant HL

29
Q

Symptoms of non-hodgkins lymphoma

A 
Night sweats
Fever
Malaise/fatigue
Wt loss
Lymphadenopathy
Splenomegaly
30
Q

Investigations for non-hodgkins lymphoma

A

FBC
Blood smear; nucleated red blood cells, left shift
Lymph node biopsy
Skin biopsy

31
Q

Treatment for non-hodgkins lymphoma

A

R-CHOP-21 + radiotherapy

Chemotherapy

32
Q

What is R-CHOP-21?

A

Used in non-hodgkins lymphoma treatment

R - rituximab
C - cyclophosphamide
H - doxorubicin hydrochloride
O -  vincristine (previously oncovine)
P - prednisolone

R-CHOP-21 is the name given if the treatment course is 3 weeks

33
Q

Symptoms of multiple myeloma

A 
Anaemia
Bone pain
Infections
Fatigue
Renal impairment
34
Q

Cells in multiple myeloma

A

Clonal proliferation plasma cells in bone marrow and typically associated w/monoclonal component in serum and/or urine

35
Q

Investigations for multiple myeloma

A

Whole body low dose CT; osteolytic lesions, pathological fractures
Serum/urine electrophoresis
Skeletal survey; osteolytic lesions, pathological fractures
Serum free light chain assey
Bone marrow aspirate and biopsy; monoclonal plasma infiltrate ≥10%
Serum calcium; hypercalcaemia

36
Q

Treatment for multiple myeloma

A

Induction therapy prior to stem cell transplant (if non-tranaplant candidate then non-transplant induction therapy)

DVT prophylaxis; i.e. aspirin

Bone disease - bisphosphonate ± analgesics

37
Q

What is myelodysplastic syndrome?

A

Group clonal stem cell disorders , ineffective haematopoeisis

Pre-leukaemic

38
Q

Symptoms of myelodysplastic syndrome

A 
Older age
Often asymptomatic
Fatigue
Exercise intolerance
Spleno/hepatomegaly
39
Q

Investigations for myelodysplastic syndrome

A

FBC
Reticulocyte count
Bone marrow aspiration with iron stain; single or multilineage dysplasia, bone marrow blasts <20%

40
Q

Treatment of myelodysplastic syndrome

A

Asymptomatic cytopenia; monitoring

Symptomatic without 5q31 deletion; haematopoietic growth factors first line, DNA methyltransferase inhibitors second line

Symptomatic with 5q31 deletion; lenalidomide first line, haematopoietic growth factors second line, DNA methyltransferse third line

41
Q

What are some myeloproliferative neoplasms?

A

Polycythaemia Vera (PV)

Essential thrombocythaemia (ET)

Idiopathic myelofibrosis (IM)

42
Q

What are the tumour markers in ALL?

A

CD34, TDT; early immature cells

43
Q

What is CAR?

A

Chimeric antigen receptor T cells

ALL treatment

44
Q

What are side effects of T cell immunotherapy?

A

Cytokine release syndrome

Neurotoxicity

45
Q

Describe cytokine release syndrome

A

Side effect of T cell immunotherapy

  • fever, hypotension, dyspnoea
  • CAR T cells correlated to presence of RRS; significant number require ITU support
46
Q

Describe neurotoxicity

A

Side effect of T cell immunotherapy

Confusion with normal conscious level

Seizure, headache, focal neurology, coma

47
Q

What is Binet staging?

A

CLL staging

A; <3 lymph node areas
B; ≥3 lymph node areas
C; B + anaemia or thrombocytopenia

48
Q

What are the most common subtypes of lymphoma?

A

Diffuse large B-cell lymphoma most common

Follicular lymphoma second most common

49
Q

Which type of infection do the different WBCs attack?

A

Neutrophils; bacterial and fungal

Monocytes; fungal infection

Eosinophils; parasitic infections

T lymphocytes; fungal and viral, PJP

B lymphocytes; bacterial infection

50
Q

What measures are used to reduce risk of sepsis in haematological malignancy?

A 
Prophylaxis
Growth factors
Stem cell rescue/transplant
Protective environment 
IV Ig replacement
Vaccination
51
Q

What are some factors in neutropenic risk?

A

Cause of neutropenia; marrow failure risk higher than immune destruction

Degree of neutropenia

  • <0.5 x 10^9 = significant risk
  • <0.2 x 10^9 = high risk

Duration
- >7days high risk

52
Q

What type of bacteria more commonly cause febrile neutropenia?

A

Gram positive bacteria

i.e. Staph, strep, enterococcus, corynebacterium, bacillus

53
Q

What are some gram negative bacteria?

A 
E.coli
Klebsiella
Pseudomonas aeruginosa
Enterobacter
Acinetobacter
Citrobacter
Stenotrophomonas
54
Q

Describe fungal infection in immunocompromised patients

A

e.g. candida, aspergillus

Life threatening deep seated infection, lung, liver, sinuses, brain

Monocytopenia and monocyte dysfunction contributes to risk of fungal infection

55
Q

Describe presentation of neutropenic sepsis

A

Fever with no localising signs

  • single reading of >38.5 or two of 38 one hour apart
  • rigors
  • chest infection/pneumonia
  • skin sepsis; cellulitis
  • UTI
  • septic shock
56
Q

How is neutropenic fever investigated?

A

History and exam
Blood cultures; Hickman line and peripheral
CXR
Throat swab and other clinical sites of infection
Sputum if productive
FBC, renal and liver function, coagulation screen

57
Q

How is neutropenic sepsis managed?

A

Resus; ABC

Broad spectrum IV abs; tazocin or gentamicin

If gram positive identified; + vancomycin or teicoplanin

If no response at 72hrs add IV antifungal e.g. caspofungin

CT chest/abdo/pelvis for source

Modify treatment based on culture

58
Q

What can cause monocytopaenia?

A

Hairy cell leukaemia, ALL, Hodgkin Lymphoma
Infections i.e. HIV, EBV
Corticosteroid or Ig therapy
Chemotherapy

59
Q

What puts patients at risk of being severely lymphopenic?

A

Stem cell transplant patients esp allogenic; Graft V Host Disease

Recipients of total body irradiation

Nucleoside analogues or ATG

Lymphoid malignancy

60
Q

Describe infection in lymphopenic patients

A

Atypical pneumonia;
- pneumonitis jirovecii, CMV, RSV

Viral
- shingles, mouth ulcers, adenovirus, EBV

61
Q

What is monitored in the blood of allogeneic transplant patients ?

A

CMV
Adenovirus
EBV

Need early intervention if become infected

Immunology and Haematology (10 decks)

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