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PATH FINAL > Haem: Myelodysplastic syndromes and Aplastic anaemia > Flashcards

Haem: Myelodysplastic syndromes and Aplastic anaemia Flashcards

1
Q

Define myelodysplastic syndrome.

A

Biologically heterogenous group of acquired haematological stem cell disorders.

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2
Q

What is the defining pathophysiological characteristics of myelodysplastic syndromes?

A
  • Development of a clone of marrow stem cell with abnormal maturation resulting in functionally defective blood cells and a reduction in cell counts
  • This leads to 3 main features:
    * cytopaenia
    * functional abnormalities of cell maturation
    * increased risk of transformation to leukaemia
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3
Q

Typicaly age range does Myelodysplastic syndromes affect

A

Elderly (>60)

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4
Q

How do myelodysplastic syndromes typically present?

A

Bone marrow failure (cytopenias) developing over weeks/months

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5
Q

List and describe some blood film and bone marrow features of myelodysplastic syndromes.

A
  • Pseudo-Pelger-Huet anomaly (bilobed neutrophils with decreased granules)
  • Dysgranulopoeisis of neutrophils (decreased granules)
  • Dyserythropoiesis of red blood cells (lack of separation between red cell precursors - cytoplasmic bridges, presence of abnormal ring of cytoplasm around the nucleus of percursor red cells)
  • Increased ring sideroblasts
  • Dysplastic megakaryocytes (micro-megakaryocytes)
  • Increased proportion of blast cells in the bone marrow BUT NOT over 20% (normally < 5%)
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6
Q

Differentiate between AML and Myelodysplastic Syndrome

A

BY DEFINITION:

Myelodysplastic < 20% blast cells in bone marrow

Myeloid > 20% blast cells in bone marrow

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7
Q

What does this image show?

A

Pelger-Huet anomaly

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8
Q

What does this image show?

A

Dysgranulopoiesis (failure of neutrophil granulation)

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9
Q

What does this image show?

A

Lack of separation between red cell precursors, presence of abnormal ring of cytoplasm around the nucleus of precursor red cells)

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10
Q

What does this image show?

A

Ringed sideroblast (accumulation of iron around the nuclei of red blood cell precursors)

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11
Q

What is the presence of myeloblasts with Auer rods suggestive of?

A

Acute myeloid leukaemia - it is pathognomonic

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12
Q

Diagnostic Criteira for Myelodysplastic Syndrome

A
  • Cytopenia of at least 1 blood cell line
  • < 20% blasts in blood and bone marrow
  • Either
    • characteristic cytogenic or molecular finding
    • morphological dysplasia >10% of nucleated cells
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13
Q

What are the four prognostic variables that are used to calculate prognostic risk using the Revised International Prognostic Scoring System (IPSS-R) for Myelodysplastic Syndromes?

A

Cytogenetics
Molecular Data
Age
Clinical data (BM blast%, cytopaenia, karyotype)

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14
Q

How does myelodysplasia tend to evolve from the time of diagnosis?

A

Blood counts will decrease (leading to worsening bone marrow failure) - *strong correlation between severity of cytopenia + overall life expectancy *

Then many develop acute myeloid leukaemia (poor prognosis)

Death causes: infection (commonest), bleeding, leukaemia

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15
Q

What are the two treatments that can prolong life in myelodysplastic syndromes?

A
  • Allogeneic stem cell transplantation
  • Intensive chemotherapy

NOTE: as most MDS patients are elderly, they often cannot tolerate treatment

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16
Q

List some other treatments that may be used in myelodysplastic syndromes.

A
  • Supportive Care (blood products, antimicrobials, growth factors (e.g. EPO, GM-CSF)
  • Biological modifiers
    • Immunosuppression
    • Azacytidine (hypomethylating agent)
    • Decitabine
    • Lenalidomide (used in 5q minus syndrome)
  • Oral chemotherapy (e.g. hydroxyurea)
  • Low-dose chemotherapy (SC low-dose cytarabine)
17
Q

Define Aplastic Anaemia

A

Inability of BM to produce adequate blood cells - damage or suppresion of stem cell or committed progenitor cell.

Note = aplastic anaemia refers to anaemia but may also include failure to produce all types of blood cells.

18
Q

List some causes of primary bone marrow failure.

A

CONGENITAL
* Fanconi anaemia (multipotent stem cell)
* Diamond-Blackfan syndrome (red cell progenitor)
* Kostmann syndrome (neutrophil progenitor)

ACQUIRED:
* idiopathic aplastic anaemia (multipotent stem cell)

19
Q

List some secondary causes of bone marrow failure.

A

Marrow infiltration
* Haematological malignancies (e.g. leukaemia, lymphoma, myelofibrosis)
* Non-haemaetological (e.g. solid tumours, mets)

Aplastic
* Infection (e.g. Parvovirus B19, TB, HIV)
* Radiation
* Drugs
* Chemicals (e.g. benzene)
* Autoimmune (e.g. SLE)

20
Q

List some drugs that can cause bone marrow failure.

A
  • Cytotoxic drugs (predicatble, dose-dependent)
  • Antibiotics - chloramphenicol, sulphonamides
  • Diuretics - thiazide
  • Antithyroid drugs - carbimazole
21
Q

Which age groups are affected by aplastic anaemia?

A

Bimodal distribution: 10-24 and 60+

NOTE: this is much more rare than MDS

22
Q

What is the most common cause of aplastic anaemia?

A

Idiopathic (70-80%)

23
Q

List some inherited causes of aplastic anaemia.

A
  • Fanconi anaemia
  • Schwachman-Diamond syndrome
  • Dyskeratosis Congenita
24
Q

Outline the possible pathophysiology of idiopathic aplastic anaemia.

A
  • Characterised by failure of the bone marrow to produce blood cells
  • Either due to an inherent issue with the stem cells (CD34, LTC-IC) and/or due to autoimmune attack on stem cells
  • Also features short telomeres
25
Q

What are some investigative features of aplastic anaemia?

A
  • Peripheral blood - cytopaenia
  • Bone marrow - hypocellular
26
Q

How is severe aplastic anaemia classified?

A

Using the Camitta Criteria
- 2 out of the following in peripheral film
- Reticulocytes = < 1%
- Neutrophils = < 0.5
- Platelets = < 20
- bone marrow biopsy = < 25% cellularity

27
Q

Outline the management approaches used for bone marrow failure in aplastic anaemia.

A
  • Seek and remove cause
  • Supportive (blood products, antibiotics, iron chelation)
  • Immunosuppressive therapy (anti-thymocyte globulin, steroids, ciclosporin A)
  • Drugs that promote bone marrow recovery (oxymetholone (androgen), thrombopoietin receptor agonist (eltrombopag))
  • Stem cell transplantation
  • Alemtuzumab (T cell depletion) - for refractory cases
28
Q

How might the age of the patient influence decisions regarding their management in aplastic anaemia?

A
  • Immunosuppressive therapies tend to be used in older patients
  • SCT tends to be used in younger patients (80% cure rate)
29
Q

List some late complications that occur after immunosuppressive therapy for aplastic anaemia.

A
  • Relapse (35% in 15 years)
  • Clonal haematological disorders - 20% risk in 10 years (myelodysplasia, leukaemia, paroxysmal nocturnal haemoglobinuria)
  • Solid tumours (3% risk)
30
Q

What is the most common cause of inherited aplastic anaemia?

A

Fanconi anaemia

31
Q

What is the inheritance pattern of Fanconi anaemia?

A

Autosomal Recessive or X-linked Recessive

32
Q

What do the gene mutations implicated in Fanconi anaemia tend to result in?

A
  • Abnormalities in DNA repair
  • Chromosomal fragility (breakage in the presence of in vitro mitomycin and diepoxybutane)
33
Q

List some somatic abnormalities that are seen in Fanconi anaemia.

A
  • Short stature
  • Hypopigmented spots/café-au-lait spots
  • Abnormality of thumbs
  • Microcephaly or hydrocephaly
  • Hypogonadism
  • Developmental delay

NOTE: these are only present in 70% of patients

34
Q

List some complications of Fanconi anaemia.

A
  • Aplastic anaemia (90%)
  • Myelodysplasia
  • Leukaemia
  • Cancer (epithelial)
  • Liver disease
35
Q

What are the characteristic features of dyskeratosis congenita?

A
  • Bone marrow failure
  • Cancer predisposition
  • Somatic abnormalities
36
Q

What are the three main somatic features of dyskeratosis congenita?

A
  • Abnormal skin pigmentation
  • Nail dystrophy
  • Leukoplakia
37
Q

Which genes are involved in dyskeratosis congenita and what are the inheritance patterns?

A
  • X-linked recessive (MOST COMMON) - DKC1 gene (defective telomere functioning)
  • Autosomal dominant - TERC (RNA components of telomerase)
  • Autosomal recessive - no mutation identified

NOTE: abnormal telomeric structure and function is heavily implicated in dyskeratosis congenita

PATH FINAL (36 decks)

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