Myelodysplastic Syndromes Flashcards
What are myelodysplastic syndromes (MDS)? What can it progress to?
Heterogeneous disorders of myeloid stem cells with ineffective hematopoiesis (RBC production)
Can progress to AML
What must be seen in bone marrow for diagnosis of MDS?
Hypercellular, abnormal maturation of cells, increased blasts (<20%, or would be leukemia)
Evidence of dysplasia in one or more cell lineages, affecting >10% of cells
What is seen on peripheral blood smear of MDS in general?
Cytopenias - with variable reduction RBCs, platelets, and granulocytes, some with functional defects.
RBCs = normocytic or **macrocytic** WBCs = abnormal nuclear lobation and granules with impaired killing activity
What is one commonly tested WBC anomaly seen in peripheral smear in MDS?
Pseudo-Pelger-Huet anomaly
- neutrophils with bilobed nuclei, and hypogranularity
- will have impaired killing activity
What is general the underlying cause of MDS?
Usually due to environmental factors such as past exposure to radiation or chemotherapy.
- Alkylating agents worst for chemotherapy
- Benzene and tobacco smoke also predipose
What genetic abnormalities and benign hematologic disease can predispose to MDS?
Genetic - Down syndrome (also predisposes to AML), Fanconi anemia, Bloom syndrome, Ataxia-Telangectasia
Hematologic - Paroxysmal nocturnal hemoglobinuria, congenital neutropenia
How do patients with MDS diagnosis present?
Usually older adults with nonspecific symptoms due to cytopenias.
Anemia symptoms most common - macrocytic
Neutropenia causes infections
Thrombocytopenia causes bleeding
How do the RBCs appear in MDS?
Macrocytic and dysplastic
- multinucleated
- dyssynchrony between cytoplasm and nucleus
- ring sideroblasts could be present
How can you track how quickly MDS is progressing to AML?
WHO classifications of refractory anemia with excess blasts
5-10% blasts - not very close
10-20% blasts - getting very close
What is the only MDS genetic variant you need to know how to treat and what is the treatment?
Isolated 5q deletion causing MDS
Treatment is lenalidomide
-> derivative of thalidomide
Note: 7q is also a common MDS variant
What other conditions can present similar to MDS (cytopenias, macrocytic anemias, etc)
Vitamin B12 / Folic acid deficiency
Heavy metal toxicity
Viral infections
Copper deficiency / Zinc excess
How are low, medium, and high risk patients with MDS treated?
Low - tranfusions and iron chelation
Medium - hypomethylating agents to stop methylation of tumor suppressors (slows progression)
High - bone marrow transplant
What is the definition of aplastic anemia and why is this name a misnomer?
Diminished or absent hematopoeitic precursors in bone marrow - usually pluripotent ones.
Misnomer because it affects all cell lines = pancytopenia
What two conditions cause congenital aplastic anemia?
- Fanconi anemia
2. Dyskeratosis Congenita - X-linked telomerase defect
What is Fanconi anemia caused by? Symptoms?
Autosomal recessive mutation in DNA repair enzymes causing chromosomal breakages and bone marrow failure
Short stature, increased cancer incidence, cafe au lait spots, thumb /radial defects
What is the most common cause of aplastic anemia / what does it usually follow?
Usually idiopathic, following acute hepatitis
What are the other causes of acquired aplastic anemia other than idiopathic?
Drug-induced
- radiation
- drugs: benzene, chloramphenicol, sulfa drugs, alkylating agents, antimetabolites
Viral - Parvovirus, HIV, EBV
What is the mechanism of action of aplastic anemia?
Damage induced by whatever cause causes lymphocyte activation
Unregulated lymphocyte activation of cytotoxic T cells directed against stem cells
What does the bone marrow and peripheral smear look like in aplastic anemia?
Everything looks normal, with cytopenias
- > otherwise would just be hypoplastic MDS
- > bone marrow looks hypocellular but otherwise normal
What gene is lost in paroxysmal nocturnal hemoglobinuria and what proteins does this prevent from being expressed on surface of cells?
PIG-A
Loss of GPI leads to loss of:
- Decay accelerating factor (DAF / CD55)
- Membrane Inhibitor of Reactive Lysis (MIRL / CD59)
These both inhibit complement. Loss leads to intravascular hemolysis
When is PNH the worst and why?
Worst at the night time
- > mild respiratory acidosis during sleep
- > Acid triggers complement
- > hemoglobinemia / hemoglobinuria can be seen in morningtime
Why is PNH included in this lecture?
It is associated with aplastic anemia, and PNH can be a component of the autoimmune reaction
What are the treatments for aplastic anemia, especially when autoimmune?
Immunosuppressive regimens: cyclosporine (blocks T cells), antithymocyte globulin
Bone marrow transplant
Transfusions and bone marrow stimulation via GM-CSF can also be tried
What cytogenetic abnormalities are present in aplastic anemia?
There should be none
-> this is what differentiates it from hypoplastic MDS
