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HEMATOLOGY-ONCOLOGY

MYELODYSPLASTIC SYNDROMES (MDS)

Myeloid neoplasm overview (Blood 2009;114:937)

•  5 categories based on BM morphology, clinical characteristics and genetics

Myelodysplastic syndromes (MDS) overview (NEJM 2009;361:1872)

•  Acquired clonal stem cell disorder → ineffective hematopoiesis → cytopeniasdysmorphic blood cells and precursors, variable risk of leukemic transformation

•  Epidemiology: >10,000 cases/y; median age ~65 y; male predominance (1.8×)

•  Idiopathic or 2° to chemo w/ alkylating agents; ↑ risk w/ radiation, benzene

•  Clinical manifestations: anemia (85%), neutropenia (50%), thrombocytopenia (40–65%)

•  Diagnosis: dysplasia (usually multilineage) in peripheral smear (ovalomacrocytes, pseudo-Pelger-Huët anomaly) and bone marrow (≥10% dysplasia with blasts ± RS)

•  Both cytogenetic [eg, del(5q), mono 7, del(7q), trisomy 8, del(20q)] and molec abnl (eg, TP53, EZH2, ETV6, RUNX1, ASXL1, SF3B1) have prognostic signif (NEJM 2011;364:2496)

•  Prior to dx MDS: exclude AML (≥20% blasts) and CMML (monocyte count >1 × 109/L); r/o 2° BM Ds due to defic. of B12, folate, copper; viral infections (eg, HIV); chemotherapy; alcohol abuse; lead or arsenic toxicity

• Rx (Am J Hematol 2012;87:692): intensity based on IPSS-R (qv), age, performance status (PS)

Poor PS, any risk → supportive care = transfusions, G-CSF, Epo, abx if needed

Low/intermediate risk → Epo (esp. if Epo level <500); lenalidomide (esp. for 5q syndrome; NEJM 2005;352:549); DNA hypomethylating agents (azacitidine or decitabine)

Intermediate/high risk → DNA hypomethylating agents (survival advantage w/ azacytidine; Lancet Oncol 2009;10:223), combination chemo (akin to AML Rx) or allogeneic HSCT if age <55 (consider reduced-intensity transplant for ages 55–75)

Hypoplastic MDS (rare) → can consider immunosuppression (CsA, ATG, prednisone)

•  Prognosis: IPSS correlates with survival and progression to AML