Myelodysplastic Syndromes + Aplastic Anaemia Flashcards
Clinical Features of Myelodysplastic Syndromes
BM failure and Cytopenias: infection, bleeding, fatigue
Hypercellular BM
Defective cells (RBC, WBC, Platelets) - expanded in later Q
How are RBC’s defective in Myelodysplastic Syndromes?
There is dyserythropoiesis of RBC: may see RING SIDEROBLASTS (abnormally nucleated blast surrounded by iron granule ring)
How are WBC’s defective in Myelodysplastic Syndromes?
Myelokathexis of neutrophils and precursors: hypogranulation, Pseudo-Pelger-Huet anomaly (bilobed/hyposegmented neutrophils)
How are platelets defective in Myelodysplastic Syndromes?
Dysplastic megakaryocytes with hypolobated nuclei, micromegakaryocytes
What are Myelodysplastic Syndromes?
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
What age group do Myelodysplastic Syndromes typically affect and how quickly do symptoms develop?
Elderly; symptoms usually develop over weeks/months
What 3 factors contribute to the prognosis of Myelodysplastic Syndromes?
BM blast % (lower is better), karyotype, degree of cytopenia
What is the Mortality rule of 1/3 for Myelodysplastic Syndromes?
1/3 die from infection, 1/3 die from bleeding, 1/3 die from Acute Leukaemia
What percentage of patients with Myelodysplastic Syndromes develop Acute Myeloid Leukemia?
50%
When does a Myelodysplastic Syndrome become AML? (in relation to blast %)
> 20% blasts = AML
under 5% = normal
What are the treatments for Myelodysplastic Syndromes?
Supportive: transfusion, SPO, G CSF, ABx
Biological modifiers: immunosuppressive drugs, Lenalidomide, Azacytidine (hypomethylating agent)
Chemotherapy: Hydroxyurea/Carbamide, Cytarabine
Allogenic SCT (Stem Cell Therapy)
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!)
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.
Blood and Bone Marrow features for Refractory Anaemia (RA)
Blood: Anaemia, no blasts
Bone Marrow: Erythroid dysplasia with less than 5% blasts
Blood and Bone Marrow features for Refractory Anaemia + Ringed Sideroblasts (RA + RS)
Blood: Anaemia, no blasts
Bone Marrow: Erythroid dysplasia with >15% ringed sideroblasts
Blood and Bone Marrow features for Refractory Cytopenia with multilineage dysplasia (RCMD)
Blood: Cytopenia in >= 2 cell lines
Bone Marrow: Dysplasia in > 10% cells in >= 2 cell lines
Blood and Bone Marrow features for RCMD + RS
Blood: Cytopenia in >= 2 cell lines
Bone Marrow: Dysplasia in >10% cells in >= 2 cell lines + >15% ringed sideroblasts
Blood and Bone Marrow features for RAEB I
Blood: Cytopenias, less than 5% blasts, no auer rods
Bone Marrow: Dysplasias, 5-9% blasts
Blood and Bone Marrow features for RAEB II
Blood: Cytopenias or 5-9% blasts, or Auer rods
Bone Marrow: Dysplasias; 10-19% blasts or Auer rods
Blood and Bone Marrow features for MDS with 5q deletion
Blood: Anaemia, normal or increased platelets
Bone Marrow: megakaryocytes with hypolobated nuclei and less than 5% blasts
Blood and Bone Marrow features for MDS Unclassified
Blood: Complex - cytopenias, no blasts, no Auer Rods
Bone Marrow: Complex - myeloid or megakaryocytic dysplasia, less than 5% blasts
What is Aplastic Anaemia?
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
What are the symptoms of Aplastic Anaemia?
Anaemia: tiredness, palor, AF, SOB etc.
Leucopenia: increased infections
Thrombocytopenia: easy bruising + bleeding problems
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?
Primary: Idiopathic (70%), Inherited (10%)
Secondary: 10 - 15%
Causes of Secondary Aplastic Anaemia
Malignant infiltration, Radiation, AI (SLE), Drugs (Chemo), Viruses (Parovirus, Viral Hep.), Benzene chemicals
4 main Inherited Aplastic Anaemias and method of inheritance. Which condition is the most common.
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
Other than AA, what are the DDx of Pancytopenia with hypocellular marrow?
Hypoplastic MDS/AML; Hypocellular ALL; Hairy Cell Leukaemia; Atypical Mycobacterial Infection; Anorexia Nervosa/Starvation; Idiopathic Thrombocytopenic Purpura
What are the Camitta Criteria for Severe Aplastic Anaemia?
Bone Marrow less than 20% cellularity + 2/3 peripheral blood features:
Reticulocytes under 1%
Neutrophils under 0.5%
Platelets under 20
Clinical Triad of Dyskeratosis Congenita
Skin pigmentation, nail dystrophy, oral leukoplakia
90% will also have BM failure
Somatic presentations of Fanconi Anaemia (found in 60-70% of cases)
Skeletal abnormalities (small thumbs), short stature, renal malformations, microopthalmia, skin pigmentation (café au lait spots, hypopigmented spots), microcephaly, hypogonadism, congenital heart defects
What 2 conditions are patients with Fanconi Anaemia at high risk of getting, and what percentage do get the conditions?
Myelodysplastic Syndrome - 30%
AML - 10%
When does Fanconi Anaemia usually present?
5-10 yrs
What is the predominant chromosomal pathology in Dyskeratosis Congenita?
Chromosomal instability: telomere shortening
What clinical symptoms may be present in Schmachman-Diamond Syndrome?
Neutrophilia - main presentation
Skeletal abnormalities, endocrine and pancreatic dysfunction, hepatic impairment, short stature
What is Diamond-Blackfan Syndrome and when does it present?
Pure red cell aplasia: normal WCC and platelets
Presents at 1yr/neonatal
