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High Yield Path - Haem > 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 are the key 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 cytopaenia, functional abnormalities of cell maturation and an increased risk of transformation to leukaemia
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3
Q

Which types of patients tend to develop myelodysplastic syndromes?

A

Elderly

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4
Q

How do myelodysplastic syndromes typically present?

A

Symptoms/signs of bone marrow failure developing over weeks/months

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5
Q

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

A
  • Pelger-Huet anomaly (bilobed neutrophils)
  • Dysgranulopoeisis of neutrophils (failure of granulation)
  • Dyserythropoiesis of red blood cells (lack of separation between red cell precursors, presence of abnormal ring of cytoplasm around the nucleus of percursor red cells)
  • Dysplastic megakaryocytes (micro-megakaryocytes)
  • Increased proportion of blast cells in the bone marrow (normally < 5%)
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6
Q

What does this image show?

A

Pelger-Huet anomaly

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7
Q

What does this image show?

A

Refractury anaemia dysgranulopoiesis (failure of neutrophil granulation)

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8
Q

What does this image show?

A

Refractory anaemia-dyserythropoiesis of red blooc cells (lack of separation between red cell precursors, presence of abnormal ring of cytoplasm around the nucleus of precursor red cells)

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9
Q

What does this image show?

A

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

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10
Q

What might you see if you stained for iron in the bone marrow of a patient with a myelodysplastic syndrome?

A

Ringed sideroblasts (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.

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12
Q

List some factors that are taken into account when classifying types of myelodysplastic syndrome.

A
  • Cell lineage affected
  • Blast cell proportions
  • Cytogenetics
  • Presence of ringed sideroblasts
  • Cytopaenia
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13
Q

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

A
  • Bone marrow blast percentage
  • Karyotype
  • Haemoglobin
  • Platelets
  • Neutrophils

NOTE: high risk is considered a score > 6, low risk ≤ 1.5

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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)

Some patients will develop acute myeloid leukaemia (poor prognosis)

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15
Q

What are the usual causes of death in patients with myelodysplasia?

A
  • 1/3 infection
  • 1/3 bleeding
  • 1/3 leukaemia
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16
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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17
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)
18
Q

List some causes of primary bone marrow failure.

A
  • 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
  • Solid tumours spreading to bone marrow
  • Radiation
  • Drugs
  • Chemicals (e.g. benzene)
  • Autoimmune
  • Infection (e.g. parvovirus B19)
20
Q

List some drugs that can cause bone marrow failure.

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

Which age groups are affected by aplastic anaemia?

A
  • All age groups (mainly 15-24 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 or due to autoimmune attack on stem cells
25
Q

What are some investigative features of aplastic anaemia?

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

How can aplastic anaemia be classified?

A

Severe or non-severe

27
Q

List some differential diagnosis for pancytopaenia and hypocellular marrow.

A
  • Hypoplastic MDS/AML
  • Hypocellular ALL
  • Hair cll leukaemia
  • Atypical mycobacterial infection
  • Anorexia nervosa
  • ITP (although Hb and RBC will be normal)
28
Q

What is the Camitta criteria for severe aplastic anaemia?

A

2 out of 3 peripheral blood features:

  • Reticulocytes < 1% (< 20 x 109/L)
  • Neutrophils < 0.5 x 109/L
  • Platelets < 20 x 109/L

Bone marrow cellularity < 25%

29
Q

Outline the management approaches used for bone marrow failure.

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
30
Q

How might the age of the patient influence decisions regardint their management?

A
  • Immunosuppressive therapies tend to be used in older patients
  • SCT tends to be used in younger patients (80% cure rate)
31
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)
32
Q

What is the most common cause of inherited aplastic anaemia?

A

Fanconi anaemia

33
Q

What is the inheritance pattern of Fanconi anaemia?

A

Autosomal Recessive or X-linked Recessive

34
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)
35
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

36
Q

List some complications of Fanconi anaemia.

A
  • Aplastic anaemia (90%)
  • Myelodysplasia
  • Leukaemia
  • Cancer (epithelial)
  • Liver disease
37
Q

What are the characteristic features of dyskeratosis congenita?

A
  • Bone marrow failure
  • Cancer predisposition
  • Somatic abnormalities
38
Q

What are the three main somatic features of dyskeratosis congenita?

A
  • Abnormal skin pigmentation
  • Nail dystrophy
  • Leukoplakia
39
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

40
Q

What are telomeres and what are their main functions?

A
  • Found at the end of chromosomes
  • Prevent chromosomal fusion or rearrangements during chromosomal replication
  • Protect genes at the end of chromosomes from degradation

NOTE: telomere length is reduced in bone marrow failure diseases (and they are especially short in dyskeratosis congenita)

High Yield Path - Haem (7 decks)

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