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Haematological Malignancies Flashcards

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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
What are the cells in Hodgkin's lymphoma?
Arises from mature B cells Characterised by presence of Hodgkin's cells and Reed-Steinberg cells
26
What are the cells in Hodgkin's lymphoma?
Arises from mature B cells Characterised by presence of Hodgkin's cells and Reed-Sternberg cells
27
Investigations for Hodgkin's lymphoma
``` FBC Metabolite panel CXR ESR Lymph node biopsy ```
28
Treatment of Hodgkin's lymphoma
Chemotherapy + Radiotherapy in classical HL Radiotherapy in early nodular lymphocyte-predominant HL Chemotherapy in late nodular lymphocyte-predominant HL
29
Symptoms of non-hodgkins lymphoma
``` Night sweats Fever Malaise/fatigue Wt loss Lymphadenopathy Splenomegaly ```
30
Investigations for non-hodgkins lymphoma
FBC Blood smear; nucleated red blood cells, left shift Lymph node biopsy Skin biopsy
31
Treatment for non-hodgkins lymphoma
R-CHOP-21 + radiotherapy | Chemotherapy
32
What is R-CHOP-21?
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
Symptoms of multiple myeloma
``` Anaemia Bone pain Infections Fatigue Renal impairment ```
34
Cells in multiple myeloma
Clonal proliferation plasma cells in bone marrow and typically associated w/monoclonal component in serum and/or urine
35
Investigations for multiple myeloma
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
Treatment for multiple myeloma
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
What is myelodysplastic syndrome?
Group clonal stem cell disorders , ineffective haematopoeisis Pre-leukaemic
38
Symptoms of myelodysplastic syndrome
``` Older age Often asymptomatic Fatigue Exercise intolerance Spleno/hepatomegaly ```
39
Investigations for myelodysplastic syndrome
FBC Reticulocyte count Bone marrow aspiration with iron stain; single or multilineage dysplasia, bone marrow blasts <20%
40
Treatment of myelodysplastic syndrome
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
What are some myeloproliferative neoplasms?
Polycythaemia Vera (PV) Essential thrombocythaemia (ET) Idiopathic myelofibrosis (IM)
42
What are the tumour markers in ALL?
CD34, TDT; early immature cells
43
What is CAR?
Chimeric antigen receptor T cells ALL treatment
44
What are side effects of T cell immunotherapy?
Cytokine release syndrome | Neurotoxicity
45
Describe cytokine release syndrome
Side effect of T cell immunotherapy - fever, hypotension, dyspnoea - CAR T cells correlated to presence of RRS; significant number require ITU support
46
Describe neurotoxicity
Side effect of T cell immunotherapy Confusion with normal conscious level Seizure, headache, focal neurology, coma
47
What is Binet staging?
CLL staging A; <3 lymph node areas B; ≥3 lymph node areas C; B + anaemia or thrombocytopenia
48
What are the most common subtypes of lymphoma?
Diffuse large B-cell lymphoma most common Follicular lymphoma second most common
49
Which type of infection do the different WBCs attack?
Neutrophils; bacterial and fungal Monocytes; fungal infection Eosinophils; parasitic infections T lymphocytes; fungal and viral, PJP B lymphocytes; bacterial infection
50
What measures are used to reduce risk of sepsis in haematological malignancy?
``` Prophylaxis Growth factors Stem cell rescue/transplant Protective environment IV Ig replacement Vaccination ```
51
What are some factors in neutropenic risk?
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
What type of bacteria more commonly cause febrile neutropenia?
Gram positive bacteria i.e. Staph, strep, enterococcus, corynebacterium, bacillus
53
What are some gram negative bacteria?
``` E.coli Klebsiella Pseudomonas aeruginosa Enterobacter Acinetobacter Citrobacter Stenotrophomonas ```
54
Describe fungal infection in immunocompromised patients
e.g. candida, aspergillus Life threatening deep seated infection, lung, liver, sinuses, brain Monocytopenia and monocyte dysfunction contributes to risk of fungal infection
55
Describe presentation of neutropenic sepsis
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
How is neutropenic fever investigated?
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
How is neutropenic sepsis managed?
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
What can cause monocytopaenia?
Hairy cell leukaemia, ALL, Hodgkin Lymphoma Infections i.e. HIV, EBV Corticosteroid or Ig therapy Chemotherapy
59
What puts patients at risk of being severely lymphopenic?
Stem cell transplant patients esp allogenic; Graft V Host Disease Recipients of total body irradiation Nucleoside analogues or ATG Lymphoid malignancy
60
Describe infection in lymphopenic patients
Atypical pneumonia; - pneumonitis jirovecii, CMV, RSV Viral - shingles, mouth ulcers, adenovirus, EBV
61
What is monitored in the blood of allogeneic transplant patients ?
CMV Adenovirus EBV Need early intervention if become infected

Immunology and Haematology (10 decks)

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