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14 Cards in this Set
- Front
- Back
Define myelodysplastic syndromes (MDS).
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Group of acquired clonal hematopoietic stem cell d/o's characterized clinically and morphologically by ineffective hematopoiesis
Typical findings: -- hypercellular dsypoietic marrow -- intramedullary cell death -- peripheral cytopenias -- tendency to progress to acute myeloid leukemia (AML) These disorders are neoplastic |
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What is dyspoiesis?
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abnormal maturation (dysplastic) of the hematopoietic precursors in BM that can be detected morphologically and fxnally
In MDS: -- all three cell lines of the marrow are involved -- severity of each line involved is variable and the basis of classification |
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Pathophys of MDS?
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Neoplastic transformation that most likely occurs at level of the earliest myeloid progenitor cell (committed progenitor cell)
-- RBCs -- megakaryocytes -- granulocytes -- monocytes Perhaps rarely at the primitive stem cell (involving myeloid AND lymphoid cells) Clonal origin proven by cytogenetic studies and X-inactivation studies Oncogenesis is a multistep process most likely involving activation of protooncogenes, inactivation of tumor suppressor genes, and mutations of antiapoptotic genes and cell cycle regulator genes. RESULT: -- impaired maturation of hematopoietic cells in marrow -- increased rate of apoptosis (above contributed to by overproduction of growth inhibitory cytokines) |
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Etiology of MDS?
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Majority are idiopathic.
Some assoc w/ know previous exposure to chemo and/or radiation --> "secondary MDS" or "therapy-related MDS" Therapy related often assoc w: -- alkylator agents (chlorambucil, malphalan, etc) -- most cases (>90%) will have partial deletions or total loss of chrom 5 and/or 7, and other complex cytogenetic aberrations May be seen in pts w/ rare inherited chrom instability syndromes: -- Fanconi's anemia -- ataxia telangectasia |
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Epidemiology of MDS?
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More common than acute leukemia, w/ a current incidence of 10/100K per year; incidence is increasing
Elderly pop affected, 65-70yrs being peak incidence. MDS seen in young adults and pediatric pts |
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MDS symptoms?
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~50% are asymptomatic at time of Dx --> MDS suspected due to abnormal CBC findings
Other symptoms related to: Anemia -- fatigue -- dyspnea -- exertion angina Leukopenia -- recurrent infections Thrombocytopenia -- ecchymoses -- petechia Hepatosplenomegaly and adenopathy are RARE |
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MDS diagnosis?
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Initally suspected by clinical findings and CBC.
Confirmed by peripheral blood smear, BM smear, and biopsy. Morphologic features of dyspoiesis assessed for each of the major cell lines Peripheral blood -- cytopenias BM -- hypercellular |
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Dyserythropoiesis
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PERIPHERAL BLOOD:
-- anemia, often macrocytic -- variable anisocytosis and poikiolocytosis -- frequently macroovalocytes -- prominent basophilic stippling sometimes present BONE MARROW: -- erythroid precursors --> varying degrees of megaloblastoid maturation -- nuclear-cytoplasmic dyssynchrony -- multinucleation -- nuclear fragmentation -- possibly ringed sideroblasts |
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Dysmyelopoiesis
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PERIPHERAL BLOOD:
-- leukopenia w/ possibly hypolobated, hypogranular PMNs (pseudo-Pelger-Huet) -- can be PMN dysfxn w/ increased infections -- Precursor cells including blasts may be in circ -- may be abnormal and immature monocytes BONE MARROW: -- come abnormal morphology w/ hypogranulation of the precursors (like seen in periphery) -- number of myeloblasts present are impt for classif and prognosis |
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Dysmegakaryopoiesis
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PERIPHERAL BLOOD:
-- thrombocytopenia -- possibly large, hypogranular platelets w/ decreased fxn BONE MARROW: -- frequently decreased numbers megakaryocytes w/ abnormal morphology -- separate, individual nuclei (instead of single, multilobated nucleus) OR -- single non-lobated nuclei AND/OR -- micro-megakaryocytes |
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MDS bone marrow biopsy?
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Hypercellular in most cases
-- 15% are hypocellular Few cases have diffuse marrow fibrosis, simulating MPD of myelofibrosis w/ myeloid metaplasia (MMM) |
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MDS cytogenetic studies?
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Approx 75% of cases will have clonal, acquired chrom aberrations
-- partial chrom deletions -- complete loss Poor prognosis assoc with: -- -7 -- presence of complex (>2 aberrations) findings Good risk findings include: -- normal karyotype -- isolated del(5q) -- isolated del(20q) All other cytogenetic findings assoc w/ intermed risk |
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Prognosis of MDS?
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Most related to
1. severity of peripheral blood 2. marrow findings at time of dx 3. cytogenetics Better prognostic types are RA and RARS (5-6yrs) Worse prognostic type is RAEB-1 (1-3yrs) |
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MDS cure?
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None
Approx 30% progress to AML Remainder succumb to complications of BM failure -- hemorrhage -- infection Trtment: -- supportive care -- transfusions -- antibiotics -- growth factors may result in temporary improvement, but does not prolong overall survival Chemo given only once transformation to AML has occurred -- low remission rate -- remission (if occurs) is of short duration BM transplant is the only possible hope for long-term remission and possible cure |