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1 J KMA Special Issue Myelodysplastic Syndrome June Won Cheong, MD Yoo Hong Min, MD Department of Internal Medicine, Yonsei University College of Medicine E mail : J Korean Med Assoc 2006; 49(10): Abstract Myelodysplastic syndrome (MDS) is a clonal stem cell disorder characterized by ineffective hematopoiesis, multilineage dysplasia, peripheral cytopenias with normocellular or hypercellular marrow, and susceptibility to leukemic transformation. MDS represents a heterogenous group of disorders with a wide spectrum of clinical, morphological, biologic, and genetic characteristics. MDS is classified according to the World Health Organization criteria and the International Prognostic Scoring System. Risk adapted treatment strategies have been developed in consideration of the advanced age of patients and to improve the clinical course of the disease. The pathophysiology, cytogenetic/molecular profiles, clinical characteristics and treatment modalities according to the prognostic groups will be described. In the future, a combination of treatment modalities to increase gene reactivation and to take advantage of increased expression of target genes may be critical to improve clinical outcomes. Multiple pathways may be involved in the MDS phenotype, and combination therapies, including novel agents, may be required to make further progresses in the treatment of this disease. Keywords : Myelodysplastic syndrome; Pathophysiology; Diagnosis; Classification; Treatment 897

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3 M y e l o d The French American British Classification of Myelodysplastic Syndromes (MDSs) Morphologic Subtype Peripheral Blood Bone Marrow MDS Diagnoses, % Refractory anemia 1% blasts 5% blasts 10~40 Refractory anemia with 1% blasts 5% blasts 10~35 ringed sideroblasts Refractory anemia with 5% blasts 5%~19% blasts 25~30 excess blasts Refractory anemia with 5% blasts OR present Auer rods 20%~29% OR present Auerrods 10~30 excess blasts in transformation Chronic myelomonocytic 5% blasts 20% blasts 10~20 leukemia 1x10 9 /L monocytes 899

4 C h e o n g The World Health Organization (WHO) Classification and Criteria for Myelodysplastic Syndromes (MDSs)* MDS Subtype(WHO) Peripheral Blood Bone Marrow FAB Subtype Anemia Isolated erythroid dysplasia RA Absent/rare blasts 5% blasts RA Anemia Isolated erythroid dysplasia RARS Absent blasts 5% blasts RARS Anemia Normal to increased megakaryocytes 5% blasts with hypolobulated nuclei MDS with (del)5q Normal to increased platelets 5% blasts RA Isolated (del)5q Cytopenias ( 2 lines) 10% dysplasia in myeloid cell Absent/rare blasts lines RCMD 5% blasts RA Monocytes, 1000/ L Cytopenias ( 2 lines) 10% dysplasia in myeloid cell Absent/rare blasts lines RCMD RS 5% blasts RARS Monocytes, 1000/ L Cytopenias Unilineage or multilineage dysplasia RAEB 1 5% blasts 5~9% blasts RAEB Monocytes, 1000/ L Cytopenias Unilineage or multilineage dysplasia RAEB 2 5%-19% blasts 10~19% blasts Present or absent Auer rods Present or absent Auer rods RAEB Monocytes, 1000/ L Cytopenias Unilineage dysplasia in granulocytes MDS unclassifiedß Absent/rare blasts of megakaryocytes 5% blasts 900

5 M y e l o d Algorithm for diagnosis and classification of MDS according to the WHO classification 901

6 C h e o n g International Prognostic Scoring System (IPSS) Prognos Score Risk Group Total Score Low 0 BM blast 5 5~10 11~20 21~30 Intermediate 1 0.5~1.0 Karyo Type* Good Intermediate Poor Intermediate 2 1.5~2.0 PB cytopenia 0/1 2/3 High 2.5 * Good = normal, Y, del(5q), del(20q), Poor = complex ( 3 abnormalities) or chromosome 7 anomalies Intermediate = other abnormalities Neutrophils 1,800/mm 3, hemoglobin 10 g/dl, platelets 100,000/mm 3 902

7 M y e l o d Survival and probability of leukemic transformation of MDS according to the IPSS risk group IPSS risk group Low Intermediate 1 Intermediate 2 High IPSS score 0 0.5~ ~ Progression to leukemia(%) 19% 30% 33% 45% Median LFS(yrs) Median Survival(yrs)

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9 M y e l o d 905

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11 M y e l o d 2. List AF, Vardiman J, Issa JP, DeWitte TM. Myelodysplastic syndrome. Hematology Am Soc Hematol Educ Program 2004; Noel P, Solberg LA Jr. Myelodysplastic syndromes. Pathogenesis, diagnosis and treatment. Crit Rev Oncol Hematol 1992; 12: Nishino HT, Chang CC. Myelodysplastic syndromes: clinicopathologic features, pathobiology, and molecular pathogenesis. Arch Pathol Lab Med 2005; 129: Bennet JM, Komrokji RS. The myelodysplastic syndrome: diagnosis, molecular biology and risk assessment. Hematology 2005; 10(suppl 1): Brunning RD, Head D, et al. Myelodysplastic syndromes. In: Jaffe S, Harris NL, et al. eds. World Health Organization Classification of Tumors; Tumors of Haematopoietic and Lymphoid Tissues. Lyon: IARC press, 2001: Korean Society of Hematology. Hematology 1st ed. Seoul: E 1. Steensam DP, Bennett JM. The myelodysplastic syndromes: Public, 2006: diagnosis and treatment. Mayo Clin Proc 2006; 81: Peer Reviewer Commentary 907

72 손용학 박찬정 서을주외 5 인 Table 1. WHO classification and criteria for the myelodysplastic syndromes[16] Disease Blood findings Bone marrow findings Refract

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