Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

IOD > haem malignancies > Flashcards

haem malignancies Flashcards

1
Q

can CML become AML

A

Yes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

can CLL become ALL

A

no

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what are the 2 categories of chronic myeloid disorders

A

myeloproliferative neoplasms

myelodysplastic syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

is myeloma a myeloid or lymphoid malignancy?

A

Myeloma is a lymphoid (B-cell) malignancy.

tumour of plasma cells which are B cell lineage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

cells categorised under myeloid lineage

A

Granulocytic – neutrophils, monocytes, eosinophils, basophils,
Erythroid (RBCs)
Platelets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

describe the development of clonal disorders of haematopoiesis

A

Genetic aberration occurring in a haematopoietic stem cell or early progenitor

Clonal expansion of the abnormal cell due to a survival or proliferative advantage

Accumulation of ‘hits’ leads to transformation to leukaemia

So both MPNs (myeloproliferative neoplasms) and MDS (myelodysplastic syndromes) can evolve into AML, and there is cross-over between MPN and MDS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

describe the philadelphia chromosome

A

Philadelphia chromosome t(9;22)
BCR-ABL fusion protein with tyrosine kinase activity
Ph’ chromosome found in the haematopoietic stem cell

causes cell proliferation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

clinical features of CML

A

Hypermetabolic symptoms – weight loss, anorexia, fatigue, night sweats
Splenomegaly (50%)
Features of bone marrow failure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

lab features of CML

A

Leucocytosis – of granulocytes, especially a basophilia
Hb and platelets may be normal or reduced
Diagnosed confirmed by bone marrow biopsy and cytogenetic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

how does imatinib work?

A

TK inhibitor
blocks downstream signalling
lifelong treatment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

define myeloproliferative neoplasm

A

A quantitative disorder (increased)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

define myelodysplastic syndrome

A

A disorder of both quality and
quantity (reduced)

Acquired neoplastic disorder of haematopoietic stem cells, characterised by increasing bone marrow failure with quantitative and qualitative abnormalities of all three myeloid lineages

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

examples of myeloproliferative neoplasms

A

Polycythaemia vera (PV)
Essential thrombocythaemia (ET)
Chronic myeloid leukaemia (CML)
Myelofibrosis (MF)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

common features of myeloproliferative neoplasms

A

Clonal proliferation

Risk of progression to AML

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

define polycythaemia vera

A

Increase in red cell volume

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

symptoms of polycythaemia vera

A

Headache, dyspnoea, blurred vision, night sweats, pruritus
Plethora, bleeding
Splenomegaly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

lab findings for polycythaemia vera

A

Raised haematocrit and Hb
WCC and platelets may also be raised
JAK2 mutation accounts for 95% of cases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

tx of polycythaemia vera

A

Venesection to Hct <0.45
Aspirin 75mg
Cardiovascular risk factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

define essential thrombocytopenia

A

Sustained increase in platelet count due to megakaryocyte proliferation
Secondary causes of thrombocytosis need to be excluded

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

clinical features of essential thrombocytopenia

A

Thrombosis or haemorrhage
Erythromelalgia ( episodes of pain, redness, and swelling in various parts of the body, particularly the hands and feet)
Splenomegaly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

management of essential thrombocytopenia

A

Cytoreduction to control platelet count – hydroxycarbamide
Aspirin
Cardiovascular risk factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

define myelofibrosis

A

Progressive generalised fibrosis of the bone marrow, associated with extramedullary haematopoieis (spleen and liver)
Abnormal megakaryocytes produce platelet derived growth factor (PDGF) and platelet factor 4 which stimulate the deposition of collagen and inhibit its breakdown
One third will have preceding PV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

clinical features of myelofibrosis

A

Anaemia symptoms
Massive splenomegaly
Constitutional / hypermetabolic symptoms

Anaemia
Initially raised WCC / platelets, but as progresses develop pancytopenia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

mx of myelofibrosis

A

Transfusion support

JAK2 inhibitor - ruxolitinib

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

risk of MDS

A

progression to AML

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

lab features of MDS

A

Peripheral blood
Red cells: macrocytosis, poikilocytosis
Neutrophils: hypogranular, pseudo Pelger
Platelet anisocytosis

BM
Hypercellular,
Dysplastic morphology in 1-3 lineages, ring sideroblasts (seen with iron stain), increased blasts

27
Q

mx of MDS

A

Transfusion support
Growth factors – GCSF, erythropoietin

Immune modulation
Chemotherapy if transformation to AML
Stem cell transplant

28
Q

define AML

A

Aggressive clonal neoplastic disorder of the bone marrow

characterised by proliferation and arrested maturation of myeloid precursor / blast cells in the bone marrow

resulting in acute bone marrow failure

29
Q

development of leukaemia

A

a multistep process

neoplastic cell is a haematopoietic stem cell or early myeloid cell

deregulation of cell growth and differentiation (associated with mutations)
proliferation of the leukaemic clone with differentiation blocked at an early stage

May arise de novo or transformation from MDS / MPN / CML

30
Q

diagnosis of leukaemia

A

BM biopsy
flow cytometry
cytogenetics
NGS

31
Q

tx of AML

A
  1. Explain diagnosis/treatment & complications
  2. Supportive care: blood products, antibiotics, antifungals, Hickman line, allopurinol, specialist unit

Chemotherapy:
anthracycline, cytarabine, targeted therapy

  1. SCT for patients with ‘high risk disease’
    (age limit due to toxicity ie GVHD, infection)
32
Q

prognosis for AML

A

Approximately 50% cure rate.

Prognosis in elderly inferior to young and fit patients

33
Q

pathophys of ALL

A

Accumulation of lymphoid blasts

34
Q

clinical features of ALL

A

BM failure, organ infiltration, including rarely testicular mass, mediastinal mass

35
Q

lab features of ALL

A

Distinguished from AML by presence of lymphoid markers, eg CD19, CD7, cCD3 rather than myeloid markers, eg CD13, CD33 on flow cytometry

Cytogenetics

The t(9;22) translocation (Ph+) is found in 20-30% of cases and is considered a poor risk feature. Imatinib incorporated in treatment

36
Q

treatment of ALL

A

Explain diagnosis/treatment & complications

  1. Supportive care: blood products, antibiotics, antifungals, Hickman line, allopurinol, specialist unit

Chemotherapy:
- extended course 2-3 years, given in blocks of combination chemotherapy, including intrathecal methotrexate

  1. SCT for patients with ‘high risk disease’ – Ph+, high WCC, adverse cytogenetics, T-ALL
    (age limit due to toxicity ie GVHD, infection)
37
Q

prognosis for ALL

A

Curable in over 90% of children, but about 40% 5 year survival in adults
Prognosis in elderly inferior to young and fit patients. Prognosis also worse at relapse.

38
Q

define CLL (chronic lymphocytic leukaemia)

A

Persistent lymphocytosis with increased mature lymphocytes

39
Q

what is the commonest leukaemia

A

CLL

40
Q

clinical features of CLL

A

Often incidental finding on routine FBC - asymptomatic
Lymphadenopathy
Hepatosplenomegaly
BM failure

41
Q

lab testing for CLL

A

Diagnosed morphologically and with immunophenotyping – CLL score
Cytogenetics – deletion or mutation of TP53 on chr 17p, associated with worse outcome
Features of haemolysis
Paraprotein – usually IgM/IgG

42
Q

tx for CLL

A 
Indolent, not curable
Options include:
Active surveillance
Oral chemo
Combination chemotherapy
Monoclonal antibodies
BCR pathway inhibitors,eg ibrutinib, idelalisib, venetoclax
Splenectomy

Most patients not fit for SCT

43
Q

define lymphoma

A

Malignant proliferation of lymphocytes that usually accumulate in lymph nodes.
Can have leukaemic phase if ‘overflows’ to blood.
Can infiltrate other organs

44
Q

aetiology of lymphoma

A

Viral – endemic – EBV, HTLV
EBV implicated in endemic Burkitt’s, HL, PTLD
Immune dysregulation – HIV, immunosuppression
Familial association

Chromosomal translocations (often involve IgH rearrangements)
Gene rearrangements / mutations 
Pro-proliferative (eg.c-Myc) or pro-apoptotic (eg. BCL2)
45
Q

clinical features of lymphoma

A 
‘B symptoms’
		- Fever, night sweats, weight loss
Malaise
Painless lymphadenopathy
Hepatosplenomegaly
Mass 
Mass effects – eg hydronephrosis
46
Q

causes of lymphadenopathy: HILLS START

A

HIV

Infection- EBV, CMV, toxoplasmosis, pyogenic infection

Lymphoma

Leukaemia

Sarcoidosis

Syphilis

TB

All disseminated malignancy

Rheumatoid arthritis

Toxicity e.g. phenytoin

47
Q

staging system for lymphoma

A

Ann arbor

I 1 lymph node group
II 2+ lymph node groups on the same side of the diaphragm
III Lymph nodes above and below the diaphragm
IV Beyond the lymph nodes, including BM

A for no B symptoms, and B if B symptoms present
E: involvement of a single, extranodal site, contiguous or proximal to a known nodal site (stages I to III only; additional extranodal involvement is stage IV)
S: splenic involvement
X:bulky nodal disease: nodal mass >1/3 of intrathoracic diameter or 10 cm in dimension

48
Q

prognosis for lymphoma

A

Depends on type of lymphoma
IN GENERAL:

Hodgkin – aggressive, but usually curable
High grade NHL – aggressive, but often curable
Low grade NHL – indolent and usually treatable, but rarely curable

49
Q

tx for lymphoma

A 
Chemotherapy
Immunotherapy – monoclonal Ab, eg Rituximab
Small molecule inhibitors
Radiotherapy
Cellular therapy – CAR-T 
Stem cell transplant
Supportive care
Palliative care

Surgery is NOT treatment of choice

50
Q

characteristic cells in hodgkin lymphoma

A

Reed sternberg

51
Q

tx for hodgkin lymphoma

A

Chemotherapy: e.g ABVD (Adriamycin, Bleomycin, Vincristine, Dacarbazine)
Monoclonal antibodies – eg brentuximab (anti-CD30)
Checkpoint inhibitors
Radiotherapy: can be curative in early stages / adjunct to chemotherapy
Stem cell transplant considered in relapse – autologous and allogeneic

52
Q

types of non-hodgkins lymphoma

A

Low grade: Follicular lymphoma
SLL/CLL
Lymphoplasmacytoid lymphoma (aka WaldenstromMacroglobulinaemia)
Marginal zone lymphoma (splenic marginal zone lymphoma and MALT)

Mantle Cell Lymphoma

High grade: Diffuse large B-cell lymphoma (DLBCL)
Burkitt lymphoma

53
Q

tx for low grade NHL

A

Low grade – active surveillance, treat if symptomatic
As for high grade
Can undergo high grade transformation
Small molecule inhibitors – BTKi, PI3Ki, BCL2i

54
Q

tx for high grade NHL

A

Chemotherapy eg. CHOP (cyclophosphamide, vincristine, adriamycin, prednisolone)
Monoclonal antibodies eg. Rituximab (anti-CD20)
Small molecule inhibitors
Radiotherapy: adjunct, palliative
Cellular therapy – CAR-T cells,
Stem cell transplant: autologous, allogeneic

55
Q

define myeloma

A

B-cell lymphoid malignancy characterised by monoclonal expansion and accumulation of abnormal plasma cells in bone marrow

56
Q

describe B cell maturation

A

Bone marrow produces naïve B-cells
Travel to lymph node and are exposed to an antigen by a APC.
Undergo somatic hypermutation of Ig genes
Leave lymph node as plasma or ‘memory’ cells and return to bone marrow.

57
Q

clinical presentation of myeloma

A

CRAB:

  • hyperCalcaemia
  • renal impairment
  • anaemia
  • bone disease

Also:
Recurrent / persistent bacterial infection
Hyperviscosity
Cord compression
Features suggestive of amyloidosis
Incidental finding of persistent raised ESR
Coagulopathy

58
Q

Ix for myeloma

A

FBC
U&E, creatinine, urate, calcium, phosphate
Liver function tests

Immunoglobulins
Serum protein electrophoresis & immunofixation
Paraprotein quantification
Serum Free light chain (SFLC) assay

Beta-2 microglobulin, LDH

Creatinine clearance
24 hour urinary protein excretion
Urinary protein electrophoresis & immunofixation
Quantification of Bence-Jones protein

59
Q

what will be seen on an electrophoresis in myeloma

A

A monoclonal (M) band seen on protein electrophoresis

60
Q

how can myeloma cause bone disease

A 
Lytic lesions
Pathological fractures
Spinal cord compression
Plain XR
Cross-sectional imaging – MRI, CT, PET C
61
Q

complications of myeloma

A 
Anaemia/bone marrow failure
Myeloma bone disease 
	-pain, pathological fractures, spinal cord compression 
Renal failure
Hypercalcaemia
Hyperviscosity syndrome
Infections
Amyloidosis 
Bleeding
62
Q

how does myeloma contribute to renal failure

A

Immunoglobulin deposition causing acute tubular necrosis
Iatrogenic: NSAIDs for bone pain, chemotherapy
Pyelonephritis
Hypercalcaemia
Hyperuricaemia
Amyloid

63
Q

tx for myeloma

A

Indolent, incurable, relapsing/remitting course

Asymptomatic – active surveillance
Steroids
Targeted therapies
proteasome inhibitors (bortezomib, carfilzomib, ixazomib)
immunomodulatory agents (thalidomide, lenalidomide, pomalidomide)
histone deacetylase (panobinostat)
monoclonal antibodies (daratumamab, elotuzomab)
Chemotherapy
Radiotherapy
Supportive care – analgesia, EPO, transfusion, dialysis
Kyphoplasty

64
Q

moa of bisphosphonates

A

Inhibit osteoclast activity by preventing osteoclast differentiation

IOD (54 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions