Table of contents
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Myelodysplastic Syndrome
- Stem cell clonal disorders characterized by ineffective hematopoiesis and various peripheral cytopenias.
- "Sick Marrow Syndrome"
- Risk of transformation to AML
- Pathophysiology:
- Reduced mature cells in periphery due to:
- 1. Disordered maturation - ineffective hematopoesis despite adequte numbers of progenitors in BM. (but usually hypercellular).
- 2. Apoptosis in BM
- 30-40% develop AML
- Reduced mature cells in periphery due to:
- Risk Factors:
- Post-chemo (esp. topoisomerase inhibitors and alkylating agents, mycophenolate - DNA damage)
- Radiation exposure
- Elderly
- DNA Repair Defects (Down's Syndrome, Fanconi Anemia)
- Incidence: 60/100,000 in >60yrs old.
- Clinical Features:
- Insidious onset - usually see pancytopenia.
- Any aplastic anemia symptoms (anemia, thrombocytopenia, neutropenia)
- Classically: Megaloblastic anemia (can be normocytic)
- Infections and bleeding not consistent with peripheral blood counts?
- On Exam:
- NO Lymphadenopathy
- NO splenomegaly
- Classification: (WHO classification)
- Many categories
- Variable survival.
- Many sideroblasts (long survival 69mo)
- 5q deletion (median survival 160mo - longest)
- Refractory Anemia With Multilineage Dysplasia (survival down to 33mo)
- Blast Numbers:
- 5-9% Blasts: "Refractory Anemia With Excess Blasts 1" (median survival 18mo)
- 10-19% Blasts: "Refractory Anemia With Excess Blasts 2" (median survival 10mo)
- 20% Blasts: AML (in past is "Refractory Anemia with Transformation")
- MDS Unclassified (survival unknown)
- Many categories
- Investigations:
- Exclude B12, Folate, Medication effects (i.e. mycophenolate), HIV
- CBC ( Anemia ± thrombocytopenia ± neutropenia. )
- Bone Marrow:
- Prognosis:
- MDS International Prognostic Scoring System (IPSS), uses 4 factors.
1. % of bone marrow blasts.
2. Karyotype (good, intermediate, poor)
3. Number of cytopenias
4. Age (<60 or >60) - Predicts outcome
- Calculate IPSS score:
- 1 - "low" (mean survival 5.7yrs)
- 2 - "interm. 1" - 1.2 yrs.
- 3 - "interm. 2" - 3.5 yrs.
- 4 - "high" - 0.4yrs.
- MDS International Prognostic Scoring System (IPSS), uses 4 factors.
- Treatment:
- Based on risk of transformation to AML
- LOW RISK
- Supportive (RBC/platelet transfusions)
- EPO SC weekly
- HIGH RISK
- Supportive (as above)
- Stem cell transplant if <65yrs.
- Epigenetic therapy (DNA methyltransferase inhibitors and histone deacetylase inhibitors).
- NOTES:
- Transfusions
- Be careful, at risk of iron overload.
- Iron chelators (only benefit in primary hemochromatosis), unclear in MDS.
- Consider if ferritin > 1000 if expected to have long survival.
- Erythropoesis Stimulating Agents (ESA)
- May be beneficial in pts with symptomatic anemia.
- Useful if EPO count not high.
- GCSF: may increase erythroid response (in addition to WBC)
- DO NOT increase risk of progression to AML
- Drugs:
- Azacitidine & another. - Pyrimidine analogue when compared to standard of care:
- Better response rate
- Decrease risk of transformation to AML
- Improves median overall survival in high risk MDS.
- Hypomethylating agents (when demethylate, improve differention to myeloid cells).
- Lenolidomide
- Effective in making transfusion (70% of pts) independence in 5q- deletion pts.
- Azacitidine & another. - Pyrimidine analogue when compared to standard of care:
- Transfusions
Sideroblastic Anemia
- Type of MDS
- Stain marrow with iron and counterstain with sapharin.
- Causes:
- Can be associated with MDS
- Congenital
- Drugs: Chloramphenicol, Isoniazid, Alcoholism
- Metabolic: Copper Deficiency, Zinc Excess
- (Both characterized by iron deficiency)
Chronic Myelomonocytic Leukemia
- Features of myelodysplastic and myeloproliferative disorder.
- (CML is a myeloproliferative disorder)
- Symptoms
- Constitutional (Wt loss, nt sweats)
- Hepatosplenomegaly
- Dx:
- Peripheral Smear (mature monocytes, leukocytosis is common)
- Monocytes > 1000 (normal 850)
- Treatment:
- Supportive.
- If WBC too high > 100,000 --> Hydroxyurea, helps constitutional sx and HSM.
- Hypomethylating agents azacitidine, (limited experience).
- Young patients (like almost all myelodysplastic syndromes) --> consider for allogeneic stem cell transplant.
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