Myelodysplastic Syndromes + Aplastic Anaemia

Question 1

Clinical Features of Myelodysplastic Syndromes

Answer 1

BM failure and Cytopenias: infection, bleeding, fatigue
Hypercellular BM
Defective cells (RBC, WBC, Platelets) - expanded in later Q

Question 2

How are RBC’s defective in Myelodysplastic Syndromes?

Answer 2

There is dyserythropoiesis of RBC: may see RING SIDEROBLASTS (abnormally nucleated blast surrounded by iron granule ring)

Question 3

How are WBC’s defective in Myelodysplastic Syndromes?

Answer 3

Myelokathexis of neutrophils and precursors: hypogranulation, Pseudo-Pelger-Huet anomaly (bilobed/hyposegmented neutrophils)

Question 4

How are platelets defective in Myelodysplastic Syndromes?

Answer 4

Dysplastic megakaryocytes with hypolobated nuclei, micromegakaryocytes

Question 5

What are Myelodysplastic Syndromes?

Answer 5

A heterogenous group of progressive disorders featuring ineffective proliferation and differentiation of abnormally maturing myeloid stem cells.
Characterized by: peripheral cytopenia, qualitative abnormalities of cell maturation; risk of AML transformation

Question 6

What age group do Myelodysplastic Syndromes typically affect and how quickly do symptoms develop?

Answer 6

Elderly; symptoms usually develop over weeks/months

Question 7

What 3 factors contribute to the prognosis of Myelodysplastic Syndromes?

Answer 7

BM blast % (lower is better), karyotype, degree of cytopenia

Question 8

What is the Mortality rule of 1/3 for Myelodysplastic Syndromes?

Answer 8

1/3 die from infection, 1/3 die from bleeding, 1/3 die from Acute Leukaemia

Question 9

What percentage of patients with Myelodysplastic Syndromes develop Acute Myeloid Leukemia?

Answer 9

50%

Question 10

When does a Myelodysplastic Syndrome become AML? (in relation to blast %)

Answer 10

> 20% blasts = AML

under 5% = normal

Question 11

What are the treatments for Myelodysplastic Syndromes?

Answer 11

Supportive: transfusion, SPO, G CSF, ABx
Biological modifiers: immunosuppressive drugs, Lenalidomide, Azacytidine (hypomethylating agent)
Chemotherapy: Hydroxyurea/Carbamide, Cytarabine
Allogenic SCT (Stem Cell Therapy)

Question 12

What are the subtypes of Myelodysplastic Syndromes, in order of progression? (May just be easier to look at the table on pg22 for this bit!)

Answer 12

Refractory Anaemia, Refractory Anaemia with Ringed Sideroblasts (RA +RS), Refractory Cytopenia with multilineage dysplasia (RCMD), RCMD + RS, Refractory Anaemia with excess blasts (RAEB I), RAEB II, RAEB III, MDS with 5q deletion, MDS Unclassified.

Question 13

Blood and Bone Marrow features for Refractory Anaemia (RA)

Answer 13

Blood: Anaemia, no blasts

Bone Marrow: Erythroid dysplasia with less than 5% blasts

Question 14

Blood and Bone Marrow features for Refractory Anaemia + Ringed Sideroblasts (RA + RS)

Answer 14

Blood: Anaemia, no blasts

Bone Marrow: Erythroid dysplasia with >15% ringed sideroblasts

Question 15

Blood and Bone Marrow features for Refractory Cytopenia with multilineage dysplasia (RCMD)

Answer 15

Blood: Cytopenia in >= 2 cell lines

Bone Marrow: Dysplasia in > 10% cells in >= 2 cell lines

Question 16

Blood and Bone Marrow features for RCMD + RS

Answer 16

Blood: Cytopenia in >= 2 cell lines

Bone Marrow: Dysplasia in >10% cells in >= 2 cell lines + >15% ringed sideroblasts

Question 17

Blood and Bone Marrow features for RAEB I

Answer 17

Blood: Cytopenias, less than 5% blasts, no auer rods

Bone Marrow: Dysplasias, 5-9% blasts

Question 18

Blood and Bone Marrow features for RAEB II

Answer 18

Blood: Cytopenias or 5-9% blasts, or Auer rods

Bone Marrow: Dysplasias; 10-19% blasts or Auer rods

Question 19

Blood and Bone Marrow features for MDS with 5q deletion

Answer 19

Blood: Anaemia, normal or increased platelets

Bone Marrow: megakaryocytes with hypolobated nuclei and less than 5% blasts

Question 20

Blood and Bone Marrow features for MDS Unclassified

Answer 20

Blood: Complex - cytopenias, no blasts, no Auer Rods

Bone Marrow: Complex - myeloid or megakaryocytic dysplasia, less than 5% blasts

Question 21

What is Aplastic Anaemia?

Answer 21

The inability of BM to produce adequate blood cells.
Typically refers to deficient RBC’s only, but patients can have a pancytopenia as well.
Hypocellular BM: Haemaopoeitic stem cell numbers are reduced in BM trephines

Question 22

What are the symptoms of Aplastic Anaemia?

Answer 22

Anaemia: tiredness, palor, AF, SOB etc.
Leucopenia: increased infections
Thrombocytopenia: easy bruising + bleeding problems

Question 23

Aplastic Anaemia is Split into Primary and Secondary. What are the 2 subsections of primary, and which is more common? What percentage of AA is secondary?

Answer 23

Primary: Idiopathic (70%), Inherited (10%)
Secondary: 10 - 15%

Question 24

Causes of Secondary Aplastic Anaemia

Answer 24

Malignant infiltration, Radiation, AI (SLE), Drugs (Chemo), Viruses (Parovirus, Viral Hep.), Benzene chemicals

Question 25

4 main Inherited Aplastic Anaemias and method of inheritance. Which condition is the most common.

Answer 25

Fanconi Anaemia - Autosomal recessive Dyskeratosis - X linked recessive (sometimes AR or AD) Schwachman-Diamond Syndrome - Autosomal Recessive Diamond Blackfan Syndrome - Autosomal Dominant with incomplete penetrance Most common = Fanconi Anaemia

Question 26

Other than AA, what are the DDx of Pancytopenia with hypocellular marrow?

Answer 26

Hypoplastic MDS/AML; Hypocellular ALL; Hairy Cell Leukaemia; Atypical Mycobacterial Infection; Anorexia Nervosa/Starvation; Idiopathic Thrombocytopenic Purpura

Question 27

What are the Camitta Criteria for Severe Aplastic Anaemia?

Answer 27

Bone Marrow less than 20% cellularity + 2/3 peripheral blood features: Reticulocytes under 1% Neutrophils under 0.5% Platelets under 20

Question 28

Clinical Triad of Dyskeratosis Congenita

Answer 28

Skin pigmentation, nail dystrophy, oral leukoplakia | 90% will also have BM failure

Question 29

Somatic presentations of Fanconi Anaemia (found in 60-70% of cases)

Answer 29

Skeletal abnormalities (small thumbs), short stature, renal malformations, microopthalmia, skin pigmentation (café au lait spots, hypopigmented spots), microcephaly, hypogonadism, congenital heart defects

Question 30

What 2 conditions are patients with Fanconi Anaemia at high risk of getting, and what percentage do get the conditions?

Answer 30

Myelodysplastic Syndrome - 30% | AML - 10%

Question 31

When does Fanconi Anaemia usually present?

Answer 31

5-10 yrs

Question 32

What is the predominant chromosomal pathology in Dyskeratosis Congenita?

Answer 32

Chromosomal instability: telomere shortening

Question 33

What clinical symptoms may be present in Schmachman-Diamond Syndrome?

Answer 33

Neutrophilia - main presentation | Skeletal abnormalities, endocrine and pancreatic dysfunction, hepatic impairment, short stature

Question 34

What is Diamond-Blackfan Syndrome and when does it present?

Answer 34

Pure red cell aplasia: normal WCC and platelets | Presents at 1yr/neonatal