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2A > haematology > Flashcards

haematology Flashcards

1
Q

what is multiple myeloma?

A

Cancer of differentiated B-lymphocytes, known as plasma cells
- production of a characteristic paraprotein

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2
Q

what is CRAB acronym, relating to myeloma?

A

-manifestations of multiple myeloma

C - Calcium elevation - Ca>0.25mmol/l above upper limit of normal or >2.75mmol/l
R - Renal impairment - creatinine>173mmol/l
A - anaemia - 2g <NR or <10g/dl
B - Bone abnormalities - lytic lesions, osteoporosis c compression, spinal cord compression

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3
Q

what do myeloma cells produced that can be detected?

A
  • intact immunoglobulin product (paraproteins) - IgG (2/3), IgA (1/3) or rarely IgD (1.8%), IgM (0.4%) or IgE
  • monoclonal free light chains
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4
Q

what is MGUS?

A

monoclonal gammopathy of undetermined significance
- non-cancerous, paraprotein made
- associated with increased risk of developing multiple myeloma
- not treated unless develops to multiple myeloma

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5
Q

what is smoulldering myeloma?

A
  • abnormal cells detected but no symptoms
  • can progress to symptomatic myeloma but at a slow rate
  • not treated until it progresses
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6
Q

what is the treatment for multiple myeloma?

A
  • combined chemotheraphy
  • stem cell transplantation
  • additional treatment - Bisphosphonates (for bones), renal dialysis, spinal cord compression treatment (radiotherapy, surgery), pain relief - to reduce symptoms and damage
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7
Q

what are the 2 types of stem cell transplants?

A
  • autologous - from patient, no rejection, for myeloma/lymphoma
  • allogeneic - from donor, rejection possibility, for blood cancers like AML, ALL, MDS
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8
Q

what is the classification of lymphoma?

A

HODGKIN LYMPHOMA or NON-HODGKIN LYMPHOMA
(if non-hodgkin lymphoma) - aggressive or idolent

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9
Q

in non-hodgkin lymphoma, what cells are effected?

A

B-cells - 90%
T-cells - 10%
NK-cells 1%

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10
Q

what are the sub-types of idolent lymphoma?

A
  • Follicular Lymphoma
  • Marginal Zone Lymphoma
  • Mantle Cell Lymphoma
  • CLL
    (all Slow growing and advanced at presentation)
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11
Q

what are the risk factors for idolent lymphoma?

A
  • Primary Immunodeficiency e.g. Wiscott-Aldrich Syndrome
  • Secondary Immunodeficiency e.g. HIV
  • Infection e.g. EBV; HTLV-1; Helicobacter Pylori
  • Autoimmune Disorders
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12
Q

what are human leukyocte antigens?

A
  • complex of genes on chromosome 6 in humans which encode cell-surface proteins
  • used to match donors in stem cell transplants
  • 6 main HLA loci –A, B, C, DP, DQ, DR
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13
Q

what are the clinical presentations of idolent lymphoma?

A
  • painless lymphadenopathy - lymph nodes swelling
  • Association with B-Symptoms – Fevers, Night Sweats and Weight Loss
  • infections
  • Compression Syndromes
  • Organ Involvement - splenomegaly, hepatomegaly
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14
Q

what are the investigations done for idolent lymphoma?

A
  • Lymph Node Biopsy – Core Needle Biopsy / Excision Node Biopsy
  • possible bone marrow biopsy
  • imaging - to determine staging classification
  • bloods
  • WHO performance status
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15
Q

what are the different treatment options for various lymphoma?

A
  • active surveillance
  • radiotherapy - local control
  • Chemoimmunotherapy - Monoclonal Antibodies/Maintenance therapy
  • Small molecules inhibitors / Novel therapies
  • Bi-Specific T-Cell engaging Antibodies and (CAR) Chimeric Antigen Receptor T Cells
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16
Q

what are some Small molecules inhibitors / Novel therapies
for idolent lymphoma?

A
  • Brutons Tyrosine Kinase Inhibitors
  • BCL2 Inhibitors
  • IMiDs
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17
Q

what is Graft-versus-Host Disease?

A

disorder that occurs when the graft’s immune cells recognize the host as foreign and attack the recipient’s body cells
- “Graft” refers to transplanted, or donated tissue
- mild to life threatning

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18
Q

what is the difference between acute vs chronic GvHD?

A

acute - skin, liver, GI tract, occurs within 100 days of stem cell transplant

chronic - any tissue, no time limit

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19
Q

what is conditioning therapy in haemopetic stem cell transplantation?

A
  • eg chemotherapy to eradicate disease and for immunosuppression
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20
Q

what is the first-line treatment for acute GvHD?

A

corticosteroids

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21
Q

what are clinical signs of GvHD?

A

mouth lesions/ulcers
rash
depends what organs effected eg diahrroea if GI

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22
Q

what is Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (vod/sos)

A
  • complication after hematopoteic stem cell transplantation
  • damage to the small blood vessels (sinusoids) in liver - causing blockage
  • clinical presentation: Jaundice
    Tender hepatomegaly
    Fluid accumulation → rapid weight gain/ascites
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23
Q

how is Veno-Occlusive Disease (VOD) / Sinusoidal Obstruction Syndrome (SOS) treated?

A
  • prophylaxis
  • defibrotide
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24
Q

what is lymphoma stage A vs B?

A

A - no ‘B’ symptoms
B - any one of ‘B’ symptoms

B symptoms - unexplained fever over 38, unexplained weight loss, drenching night sweats

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25
Q

what additional clinical investigations are needed for lymphoma?

A
  • FBC - white blood cells eg lymphocytes
  • organ functions - LFTs, RFTs indicate involvement
  • viral screen - eg HIV, HepB/C
  • G6PD - RBC function, treatment may cause hemolysis
  • uric acid - high levels indicate cell breakdown
  • LDH - elevated indicates more aggressive
  • Beta- 2 microglobulin - as above
  • ESR - may indicate inflammation, nonspecific
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26
Q

what are the treatment options for high grade lymphoma?

A

Immunochemotherapy, autograft
Radiotherapy
Allograft - transplanting stem cells
Check Point Inhibitors - immunotherapy targeting cancer and T-cells
BITE - Bispecific T-cell Engagers - t-cells attack cancer
CAR-T/NK - Chimeric Antigen Receptor engineered to be expressed in T-cells/Natural Killer cells

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27
Q

what are the main types of hodgkin lymphoma?

A

classical Hodgkin lymphoma - subclasses include Nodular sclerosis, Mixed cellularity

nodular lymphocyte-predominant Hodgkin lymphoma

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28
Q

what cells are found in hodgkin lymphoma?

A

Reed-Sternberg cell

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29
Q

what is the treatment for hodgkin lymphoma stage 1-2a vs 2b-4?

A

Stage 1-2A
- Short course combination chemotherapy - ABVD followed by radiotherapy

Stage 2B-4
- intensive chemotherapy, more cycles - ABVD
- radiotheraphy only selectively used

30
Q

what is ABVD?

A

combinatoin of drugs in chemotherapy used to treat lymphoma
- doxorubicin, bleomycin, vinblastine, dacarbazine

31
Q

what are the features of idolent NHL?

A
  • incurable
  • slow growing
32
Q

what is diffuse large B cell lymphoma an example of?

A

aggressive/high grade non-hodgkin lymphoma

33
Q

what are Myelodysplastic Syndromes?

A

blood cancers that affect the bone marrow
- Bone marrow cells fail to make adequate numbers of healthy blood cells
- risk factor for AML

34
Q

what is Acute Myeloid Leukaemia characterised by?

A
  • immature myeloid cell proliferation (defined as ≥20% “blasts”)
  • bone marrow failure
35
Q

what does a FBC show in myledoplastic syndromes?

A
  • low blood count (red/white cells & platelets)
  • Peripheral blood film demonstrates dysplastic features (e.g. hypogranular neutrophils)
36
Q

what does a FBC show in acute myeloid lymphoma?

A
  • white blood cells can be normal/high/low
  • red blood cells, and platelets usually low
37
Q

what are differential diagnosis of AML/ MDS?

A
  • B12/ folate or mixed haematinic deficiency
  • Infection (e.g. retroviral disease, herpesvirus)
  • Medications
  • Autoimmune
  • Liver disease (e.g. cirrhosis)
38
Q

what are important investigations in MDS/AML?

A
  • history
  • review previous FBC - is there a downward trend?
  • FBC and blood film
  • Haematinics (B12, folate, ferritin)
  • high uric acid and LDH
  • blasts in peripheral blood are key indicator
39
Q

whatare the investigations for AML?

A
  • Blood tests (full blood count & blood film)
  • Bone marrow aspirate and trephine biopsy
  • Immunophenotyping, Cytogenetics, Fluorescence in situ hybridisation (FISH), Molecular analyses
40
Q

what conditions are associated with MDS/AML?

A
  • anaemia
  • neutropenia - low neutrophils
  • thrombocytopenia low platelets
41
Q

what is the treatment of AML?

A
  • chemotherapy - Azacytidine
    (Low dose subcutaneous cytarabine - non-curative for less fit people)
  • supportive measures eg fertility cryopreservation, blood transfusion
  • hematopoietic stem cell transplantation after chemo for high risk relapse
42
Q

what are the classifications of anaemia by cell size?

A
  • Microcytic
  • Normocytic
  • Macrocytic
43
Q

what is normal haemoglobin level in females/males?

A

females - 115-165 g/L

males - 130-180 g/L

44
Q

what does Reticulocyte count show?

A

meaures immature red blood cells; measure of rate of red blood cell production
- for determining whether normocytic anaemia is resulting from increased destruction of RBCs or decreased production
- low count shows bone marrow isn’t producing RBC - bone marrow disease or iron deficiency

45
Q

what in the normal amount of haemoglobin in cells?

A

27-33pg

46
Q

what investigations are required when testing for anaemia?

A
  • FBC with Mean Corpuscular Volume (MCV) to determine size to classify
  • b12
  • folate
  • ferritin
  • serum iron
  • TIBC - total iron-binding capacity
  • LFT/KFT
47
Q

in folate/b12 deficiency, what needs to be started first?

A

b12

48
Q

what are the causes for microcytic vs normocytic vs macrocytic anaemia?

A
  • Microcytic:
    Iron deficiency
    Thalassaemias
  • Normocytic:
    Chronic disease
    Renal disease
    (acute bleeding)
  • Macrocytic:
    Folate deficiency
    B12 deficiency
    Haemolysis
    Bone marrow disorders
49
Q

what are the causes of iron deficiency?

A
  • blood loss
  • GI - coeliac
  • menstrual
  • dietary deficiency eg vegans
  • pregnancy
50
Q

what is normal MCV (Mean corpuscular volume)?

A

80-98fl

51
Q

what are symptoms of anaemia?

A

Pallor
Fatigue
Breathlessness
Dizziness
Palpitations
Cold hands and feet

52
Q

what is sickle cell disease?

A

single point mutation in beta globin gene
- autosomal recessive
- abnormal haemoglobin
- can block blood vessels causing ischaemia

53
Q

how is sickle cell diagnosed?

A
  • Sickle solubility test - quick test shows presence of HbS
  • Haemoglobin electrophoresis - shows different Hb and HbS proportion
54
Q

what are some complications of sickle cell?

A
  • venoocclusive crisis - severe pain - analgesia
  • stroke
  • leg ulcers
  • acute anaemia
  • gallstones
  • acute chest syndrome - high risk mortality
  • Sequestration crisis
55
Q

what is the treatment for sickle cell disease?

A
  • preventative measures - eg warm, hydrated, vaccinated
  • Hydroxycarbamide - increases HbF levels
  • New drugs: crizanlizumab, voxelotor
  • Regular blood transfusion - top-up and exchange
  • allogeneic bone marrow transplant - potentially curative- rarely used due to high mortality
  • gene therapy
56
Q

what is Thalassaemia?

A

reduced Hb production
- alpha/ beta thalassaemia
- autosomal recesisve
- carriers - microcytic, may have mild anaemia

57
Q

what is the management of thalassaemia (beta major)?

A
  • red blood cell transfusion
  • Monitoring of iron status and iron chelation therapy - avoid iron overload
  • Folic acid (5mg daily)
  • monitor organ systems
58
Q

what is the difference between alpha thalassaemia major and minor?

A

minor - 1/2 genes affected, usually asymptomatic

major - death in utero

59
Q

what is haemoglobin H disease?

A
  • 3 alpha goblin genes affected
  • moderate anaemia
  • severity of symptoms varies
60
Q

what are the 3 major criteria for diagnosing polycythaemia vera?

A
  • Hb over 16.5g/dL in men or 16g/dL in women
    or increased red blood cell mass
  • bone marrow tri-lineage proliferation with pleomorphic mature megakaryocytes - increase in red cells, white cells, and platelets in the bone marrow
  • presence of JAK2 mutation
61
Q

what is the minor criteria for diagnosing polycythaemia vera?

A
  • low serum erythropoietin level
  • if normal bone marrow histology required
62
Q

how is polycythemia vera distinguished between low vs high risk?

A

low risk - no history of thrombosis, under 50
high risk - history of thrombosis, over 50

63
Q

what is thrombocytosis?

A

platelet levels are above normal

64
Q

what is thrombocythaemia?

A

chronic myeloproliferative neoplasm (MPN) associated with an increase in number and size of circulating platelets

65
Q

what is myelofibrosis?

A
  • type of myeloproliferative neoplasm
  • bone marrow disorder
66
Q

what is the major criteria for myelofibrosis to be diagnosed?

A
  • presence of JAK2, CALR, MPL or other clonal markers
  • not meeting criteria for other myeloid neoplasms
  • bone marrow fibrosis grade 2 or over
67
Q

what is the minor criteria for myelofibrosis to be diagnosed?

A
  • anemia with no other explanation
  • Palpable Splenomegaly
  • Increased Serum Lactate Dehydrogenase (LDH) Level
  • leukocytosis
68
Q

what are the treatment option for myelofibrosis?

A
  • JAK inhibitors
  • Erythropoietin
  • blood transfusions
  • Androgens to stimulate blood cell production
69
Q

what does Erythropoietin most commonly treat?

A

anemia

70
Q

what are the treatment options for CML(Chronic myelogenous leukemia)?

A
  • Imatinib - tyrosine kinase inhibitor
  • Interferon-alpha (IFN-α) immunotherapy
  • Hematopoietic Stem Cell Transplantation - in aggressive cases
71
Q

what investigations are required for CML?

A
  • bone marrow biopsy
  • karyotyping - BCR-ABL1 measured
  • FBC
72
Q

what cell do monocytes, basophils, eosinophils and neutrophils originate from?

A

myeloblast
- from common myeloid progenitor from hematopoietic stem cell

2A (9 decks)

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