Brainscape's Knowledge GenomeTM

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


See full index

PATHOLOGY > myelodysplastic syndrome > Flashcards

myelodysplastic syndrome Flashcards

1
Q

what are myelodysplastic syndromes

A

Biologically heterogeneous group of acquired haemopoietic stem cell disorders

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

what are myelodysplastic syndromes characterised by

A

development of a clone of marrow with abnormal maturation ->
* functionally defective nlood cells
* numerical reduction in blood cells ->

cytopenia
functional abnormalities of erythroid, myeloid and megakaryocyte maturation
increased risk of transfromation into leukaemia because stem cell disorder

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

summarise myelodysplasia

A

disorder of elderly
sx - general marrow failure
slow developing - over wks/mos

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

blood and bone marrow features of myelodysplasia

A
  • Pelger-Huet anomaly (bilobed neutrophils)
  • Dysganulopoieses of neutrophils (abnormal number of granules)
  • Dyserythropoiesis of red cells (not nice and round)
  • Dysplastic megakaryocytes – e.g. micro-megakaryocytes (bone marrow biopsy – make plts look abnormal)
  • Increased proportion of blast cells in marrow (normal < 5%) – normally only have a small number of. In AML – blast cells proliferate, don’t differentiate and eradicate normal marrow
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q
A

normal neutrophils

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

Pelger-Huet anomaly
(myelodysplasia)

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

refractory anaemia dysgranulopoiesis
myelodysplasia

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

myelokathexis - pyknotic nuclei and lengthening and thinning of intrasegmented filaments and vacuoles
it is an increased number of mature adn hypersegmented neutrophils

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

refractory anaemia dyserythropoeisis
(myelodysplasia)

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

ringed sideroblasts in bone marrow
stain bone marrow for iron
some of red cell precurser contain siderotic granules around nucleus - here there are two many ie ringed sideroblast
myelodysplastic syndrome

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

myeloblasts with Auer rods
precurser of AML
Primative cells with no granules

Auer rods – long red purple intracytoplasmic bodies – only AML

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

classification of myelodysplastic syndrome

A
  • Number of dysplastic lineages
  • Percentage of blasts in bone marrow and peripheral blood
  • Cytogenetic findings
  • Percentage of ringed sideroblasts
  • Number of cytopenias (based on criteria from the International Prognostic Scoring System - IPSS)
    Hb < 100 g/L
    Platelets < 100 x 10^9/L
    Neutrophils < 1.8 x10^9/L
    Monocytes < 1.0 x 10^9/L (if > 1.0 x 10^9/L then diagnosis is CMML)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

importance of classifcation of myleodysplastic syndromes

A

has prognostic significance

note - started to take into account molecular changes

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

prognostic scoring system for myelodysplastic syndromes

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

how does the prognostic score lead to outcomes for myelodysplastic syndrome

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

what are the driver mutations in myelodysplastic syndrome

A

Driver mutations - carry prognostic significance:
TP53, EZH2, ETV6, RUNX1, ASXL1
Others: SF3B1, TET2, DNMT3A

most common mutations are more in high risk MDS than in low risk

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

natural evolution of myelodysplasia

A

deterioration of blood counts -> worsening consequences of marrow failure
development of AML (depends on risk) - worse Px than spontaneous AML presumably because all stem cells have been effected

1/3 die from infection
1/3 die from bleeding
1/3 die from acute leukaemia

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

treatment of myelodysplastic syndrome that prolonges survival

A

allogenic stem cell transplant (SCT)
intensive chemo

only a minority get them - most are too old, there is high mortality from SCT

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

treatment of MDS

A

supportive care:
* blood product support
* antimicrobial therapy
* growth factors - (Epo (for RBC), G-CSF (for neutrophils), TPO-Receptor Agonist (for plts))

Biological modifiers
* immunosuppressive therapy
* Azacytidine and decitabine - Hypomethylating agents, enhance marrow function
* Lenalidomide (for del(5q) variant of MDS) – biological response modifier
* oral chemo - if white cell is high (unusual) - use hydroxyurea/hydroxycarbamide
* low dose chemo in past
* intensive chemo/SCT for high risk MDS - give AML like regimen. Allo/VUD standard/ reduced intensity

20
Q

summarise the haematopoietic cell lines

A

multipotent stem cell - in very small numbers in marrow. - give rise to progenitor cells
progenitor cells have proliferative ability

21
Q

summarise how where in the cell lineage that the marrow failure effects alters the outcome

A

marrow failure is from damage/suppression of a stem/progenitor cell

pluripotent haematopoietic cell impairs production of all peripheral blood cells - rare

committed progenitor - results in bi- or unicytopenias

22
Q

causes of primary bone marrow failure

A

Congenital: Fanconi’s anaemia (multipotent stem cell)

Diamond-Blackfan anaemia (red cell progenitors) - children

Kostmann’s syndrome (neutrophil progenitors) - children

Acquired: Idiopathic aplastic anaemia (multipotent stem cell) – most common

23
Q

causes of secondary bone marrow failure (more common than primary)

A

Marrow infiltration:
Haematological (leukaemia, lymphoma, myelofibrosis)
Non-haematological (Solid tumours, secondary fibrosis)
Radiation
Drugs
Chemicals (benzene)
Autoimmune
Infection (Parvovirus, Viral hepatitis, HIV)

24
Q

drugs that can cause bone marrow failure

A

PREDICTABLE bone marrow suppression (dose-dependent, common) - Cytotoxic drugs
IDIOSYNCRATIC (NOT dose-dependent, rare)
* Phenylbutazone (NSAID)
* Gold salts (for rheumatoid arth)

ANTIBIOTICS
* Chloramphenicol
* Sulphonamide – often when already unwell with haem disease

DIURETICS - Thiazides
ANTITHYROID DRUGS - Carbimazole

25
Q

epidemiology of aplastic anaemia

A

rare
all age groups can be effected
peak incidence 15-24yrs, and >60yrs

26
Q

classification of aplastic anaemia

A

idiopathic - majority
inherited
secondary
miscellaneous

27
Q

causes of inherited aplastic anaemia

A

Dyskeratosis congenita (DC)
Fanconi anaemia (FA)
Shwachman-Diamond syndrome – children

28
Q

secondary causes of aplastic anaemia

A

radiation
drugs
* predictable - cytotoxic agents
* idiosynchratic - choramphenicol, NSAIDs

viruses - idiosynchratic - hepatitis
immune - SLE

29
Q

miscellaneous causes of aplastic anaemia

A

paroxysmal nocturnal haemoglobinuria
thymoma

30
Q

pathophysiology of idiopathic aplastic anaemia

A

failure of marrow to make cells
stem cell problem (CD34, LTC-IC) [Long-Term Culture-Initiating Cells]

immune attack - humoral or cellular attack against multipotent haematopoietic stem cell probs triggered by viral infection - response to virus cross react with stem cell

31
Q

clinical presentation of aplastic anaemia

A

anaemia - fatigue, breathlessness
leucopenia - infections
platelets - easy bruising/bleeding

32
Q

diagnosis of aplastic anaemia

A

blood - cytopenia
marrow - hypocellular

classified as severe aplastic anaemia
or non-severe aplastic anaemia

33
Q

if L is normal marrow what is R

A

aplastic

34
Q

what is severe aplastic anaemia

A

Camitta criteria:

2 out of 3 peripheral blood features

  1. Reticulocytes < 1% (<20 x 109/L)
  2. Neutrophils < 0.5 x 109/L
  3. Platelets < 20 x 109/L

Bone marrow <25% cellularity

35
Q

Mx of bone marrow failure

A

treat cause
blood/plt transfusions (leucodepleted, CMV negative, irradiated)
abx
iron chelation - if need many transfusions (when ferritin >1000)

Immunosuppressive therapy (anti-thymocyte globulin, steroids, eltrombopag, cyclosporine A) – because due to immune mediated pathway

drug to promote marrow recovery - Oxymethone, TPO receptor agonists (eltrombopag), ??G-CSF (prob not).

stem cell transplant

in refractory cases - alemtuzumab (anti-CD52, high dose cyclophosphamide)

36
Q

specific rx for idiopathic aplastic anaemia

A

based on severity, age and whether potential sibling donor

immunosuppressive therapy if older - Anti-Lymphocyte Globulin (ALG), Ciclosporin, Eltrombopag (a BM stimulating agent)

androgens - oxymethone

SCT - younger pt with donor = 80% cure, VUD/MUD for > 40 yrs (50% survival)

37
Q

late complications following immunosuppressive therapy for aplastic anaemia

A

relapse of aplastic anaemia - 35% over 15yrs

clonal haematological disorders - myelodysplasia, leukaemia, paroxysmal nocturnal haemoglobinuria

development of solid tumours

38
Q

summarise fanconi’s anaemia

A

most common form of inherited aplastic anaemia
autosomal recessive or X linked
multiple mutated genes are responsible
when genes mutated -> abnormalities in DNA repair, chromosomal fragility (breakage in presence of in-vitro mitomycin or diepoxybutane)

39
Q

congenital abnormalities in fanconis anaemia

A

Short Stature
Hypopigmented spots and café-au-lait spots
Abnormality of thumbs
Microcephaly or hydrocephaly
Hyogonadism
Developmental delay

no abnormalities in 30%

40
Q

complications of fanconis anaemia

A
Rate of aplastic anaemia very high – and get by age 10
41
Q

summarise dyskeratosis congenita

A

inherited disorder characterised by** marrow failure, cancer predisposition and somatic abnormalities **

classical triad
* skin pigmentation
* nail dystrophy
* leukoplakia - white patches on tongue

42
Q

mx for DYSKERATOSIS CONGENITA

A

normal mx for marrow failure

future - haemopoietic gene therapy

43
Q

genetic basis of DYSKERATOSIS CONGENITA

A

3 patterns of inheritence
abnormal telomeric structure and dunction is implicated
telomeres are
* at end of chr
* prevent chr fusion or rearrangement during replication
* protect genes at end of chr from degradation

length os reduced in marrow failure disease

44
Q

patterns of inheritence in DYSKERATOSIS CONGENITA

A

x linked recessive - most common - mutated DKC1 gene - defective telomerase function

Autosomal dominant trait — (mutated TERC gene - encodes the RNA component of telomerase).

Autosomal recessive trait

45
Q

comparison of dyskeratosis congenita and idiopathic aplastic anaemia

A

Both potentially susceptable to other malignancies

Idiopathic don’t get physical abnormalities

46
Q

treatment algorithm for severe aplastic anaemia

A

Young and have donor – transplant
Older – immunosuppress – only transplant if immunosuppression doesn’t work

PATHOLOGY (94 decks)

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