Intro to MDS and MPN Flashcards
Usual presentation of MDS
Older patients (60/70+)
Asymptomatic
In the advanced stage, may see easy bruising/bleeding, fatigue/SOB, fever, infection
What are you gonna see on a PBS for MDS?
Hypolobulated neutrophil
RBC macrocytosis
How to confirm the diagnosis of MDS?
Bone marrow aspirate/biopsy
Often shows a hypercellular bone marrow and the marrow cells show dysplastic features
What is MDS?
Clonal disorder affecting hematopoietic maturation (a type of blood cancer)
Characterized by ineffective hematopoiesis
Bone marrow failure with resultant cytopenias
Pathogenesis of MDS
Ineffective hematopoiesis
The marrow is trying to make new cells, but the dysplasia shows that cell development is abnormal
Many cells die before they can leave the marrow
Patients become cytopenic (anemic, thrombocytopenia) even though the marrow is hypercellular
Invisible brake
Blood cells arent making it out of the marrow
Ineffective hematopoiesis from hypercellular marrow
In MDS
3 risk factors for MDS
Age (more in older)
Exposure to organic compound (like benzene and toluene)
Cigarette smoking
Complications of MDS
Fatigue, bleeding and infection due to cytopenia
Progression to AML (worse than just getting AML de novo)
3 ways to treat MDS
Supportive and symptomatic (transfuse RBCs and platelets when needed)
Chemo
Allogeneic stem cell transplant (only for young patients)
Left shift
Increase numbers of immature cells in the blood
Continuum of developing cells
When the marrow is working very hard
Common presentation of MPN
Incidental finding of abnormal blood counts
Symptoms: fatigue, weight loss, night sweats, abdominal fullness (from splenomegaly), anorexia
4 types of myeloproliferative disorders
CML
Polycythemia vera
Essential thrombocytosis
Idiopathic myelofibrosis
CML pathophys
Malignant clonal disorderof pluripotent stem cells
Increased granulocytic cells (often there is also increased erythroid and platelet lines)
Philadelphia chromosome
Philadelphia chromosome
Translocation of chromosomes 9 and 22
Creates a fusion of BCR-ABL gene (oncogene)
Seen in CML
3 phases of CML
Chronic phase
Accelerated phase
Blast crisis
CML treatment
Tyrosine kinase inhibitor
Specific targeted therapy against BCR-ABL
Improves life expectancy compared to previous therapy
Ex: Imatinib
What is polycythemia
Elevated hematocrit
Can have several causes
Spurious: dehydration (increased HCT from low plasma volume)
True: secondary polycythemia can be from hypoxia or high EPO
Polycythemia vera pathophys
Excessive RBC production from an abnormal marrow, without EPO stimulation
Mutated JAK2 protein binds to the EPO receptor
Binding promotes signalling independent of EPO stimulation and hypersensitivity to cytokine
Clinical presentation of complications of PV
Facial plethora, erythromelalgia Increased blood viscosity (thrombosis) Platelet dysfunction (unusual bleeding) Elevated histamine (itch and PUD) Increased uric acid (gout) Progression to myelofibrosis and AML
Treatment of PV
Phlebotomy to maintain HCT under 45%
ASA once a day
Essential thrombocytopenia
Very high platelet counts
Negative philadelphia chromosome, can be JAK2 positive
Platelets can be functional or dysfunctional (patients can clot or bleed)
Treatment for essential thrombocytopenia
Aspirin
Hydroxyura
Ruxotinib (to target the JAK2 mutation)
Myelofibrosis
Fibrosis fills the marrow space in idopathic myelofibrosis (IMF)
Patients become cytopenic because there is less hematopoiesis
MPN
Excessive unregulated proliferation of myeloid cells
