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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1 대한진단검사의학회지 : 제 23 권제 2 호 2003 Korean J Lab Med 2003; 23: 71-7 진단혈액학 한국인골수이형성증후군환자들에대한 FAB 분류와 WHO 분류의비교및 WHO 분류의유효성 손용학 박찬정 서을주 이정희 1 이제환 1 이규형 1 이정신 1 지현숙 울산대학교의과대학서울아산병원진단검사의학과, 내과 1 Comparison of FAB and WHO Classifications and Validation of WHO Classifications in 218 Korean Patients with Myelodysplastic Syndrome Yong-Hak Sohn, M.D., Chan Jeoung Park, M.D., Eul Ju Seo, M.D., Jung-Hee Lee, M.D. 1, Je-Hwan Lee, M.D. 1, Kyoo-Hyung Lee, M.D. 1, Jung-Sin Lee, M.D. 1, and Hyun Sook Chi, M.D. Departments of Laboratory Medicine and Internal Medicine 1, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea Background : World Health Organization (WHO) proposed a new classification of myelodysplastic syndrome (MDS) in 1999, based on significant modifications of the original FAB proposals. The aim of the present study was to validate the new classification with respect to prognostic importance. Methods : Two hundred and eighteen patients were diagnosed with MDS according to the FAB criteria between August 1989 and June 2001 in the Asan Medical Center. They were studied retrospectively to evaluate morphological, clinical and cytogenetic data for diagnosis and clinical outcomes with long-term follow up, and reclassified with a new WHO classification. Results : According to the original FAB classification, 218 patients were classified as RA 78, RARS 17, RAEB 76, RAEB-t 38 and CMML 9. They were reclassified to the WHO classification to RA 24, RARS 6, RCMD 51, RCMD-RS 11, RAEB-1 42, RAEB-2 51, del(5q) syndrome 1 and unclassifiable 2. Twenty-one cases of RAEB-t and 9 cases of CMML were reclassified to acute myeloid leukemia and myelodysplastic syndrome/myeloproliferative disease (MDS/MPD). Among the reclassified groups in the WHO classification, there is a significant difference in prognosis between RA and RCMD (median survival, not reached vs months, P=0.020), and in leukemic transformation between RAEB-1 and RAEB-2 (5% vs. 37%, P=0.001). Conclusions : These data provide the proper evidence, especially of prognosis and leukemic transformation for the WHO classifications. We recommended using the WHO classification rather than the FAB classification of the diagnosis of MDS. (Korean J Lab Med 2003; 23: 71-7) Key Words : Myelodysplastic syndrome, FAB classification, WHO classification 서 론 접수 : 2003년 1월 18일접수번호 : KJCP1646 수정본접수 : 2003년 3월 19일교신저자 : 박찬정우 서울특별시송파구풍납2동 서울아산병원진단검사의학과전화 : , Fax: cjpark@amc.seoul.kr 1982년 FAB group은말초혈액과골수의형태학적소견에기초하여골수이형성증후군 (myelodysplastic syndrome, MDS) 의분류기준을제안하였다 [1]. 이분류에기초하여골수이형성증후군에관한많은임상적인연구와세포형태학적인연구가시 71

2 72 손용학 박찬정 서을주외 5 인 Table 1. WHO classification and criteria for the myelodysplastic syndromes[16] Disease Blood findings Bone marrow findings Refractory anemia (RA) Anemia Erythroid dysplasia only No or rare blasts <5% blasts <15% ringed sideroblasts Refractory anemia with ringed Anemia Erythroid dysplasia only sideroblasts (RARS) No blasts >15% ringed sideroblasts <5% blasts Refractory cytopenia with Cytopenias (bicytopenia or pancytopenia) Dysplasia in 10% of cells in 2 or more myeloid cell lines multilineage dysplasia (RCMD) No or rare blasts <5% blasts in marrow < /L monocytes <15% ringed sideroblasts Refractory cytopenia with Cytopenias (bicytopenia or pancytopenia) Dysplasia in 10% of cells in 2 or more myeloid cell lines multilineage dysplasia and ringed No or rare blasts 15% ringed sideroblasts sideroblasts (RCMD-RS) <5% blasts in marrow < /L monocytes Refractory anemia with excess Cytopenias Unilineage or multilineage dysplasia blasts-1 (RAEB-1) <5% blasts 5% to 9% blasts No Aurer rods < /L monocytes Refractory anemia with excess Cytopenias Unilineage or multilineage dysplasia blasts-2 (RAEB-2) 5% to 19% blasts 10% to 19% blasts Auer rods ± Aurer rods ± < /L monocytes Myelodysplastic syndrome, Cytopenias Unilineage dysplasia in granulocytes or megakaryocytes unclassified (MDS-U) No or rare blasts <5% blasts MDS associated with Anemia Normal to increased megakaryocytes with hypolobulated nuclei isolated del(5q) <5% blasts <5% blasts Platelets normal or increased Isolated del(5q) 행되어왔다. 많은연구들이이 FAB 분류기준이진단적인유용성이있고, 예후에도영향이있음을보고하였다 [2-6]. 그리하여 18년동안 FAB 분류기준은골수이형성증후군의세포형태학적인기준이되어왔다. 그러나, 동시에여러가지모순점들이보고되어왔다 [7]. 첫째는만성골수단핵구성백혈병 (chronic myelomonocytic leukemia, CMML) 의많은증례에서임상적및혈액학적특징이골수증식성질환의특징과유사하게나타냄을보여주고있어서 [8, 9], 이를골수이형성증후군으로포함시켜야하는지의문제이다. 또다른문제는아세포과다불응성빈혈 (Refractory anemia with excess blasts, RAEB) 군이예후적인면에서상당히다른여러군들을포함하고있다는것이다 [3]. 또한 Rosati[10], Matsuda 등 [11] 은불응성빈혈 (refractory anemia, RA) 군이형태및예후에서동일한양상을보이지않음을보여주었고, RA 군을다계열이형성을보이는 RA 군과적혈구에만이형성이국한되어있는 RA 군으로나누자고제안하였다. 환형철적아구성불응성빈혈 (refractory anemia with ringed sideroblasts, RARS) 군에서도이형성의정도에따라두개의군으로나누었을때, 형태및예후의차이가있다는보고가있었다 [12, 13]. 이외에도골수이형성증후군의어떤군에도속하지않는증례 (unclassifiable MDS) 들이보고되어져왔다. 이러한문제점을보완하여 WHO는최근에골수이형성증후 군의새로운분류기준을제안하였다 [14-16](Table 1). 이에저자들은국내단일병원에서 12년동안추적관찰된골수이형성증후군환자를대상으로 FAB 분류와새로제안된 WHO 분류기준을비교하고, WHO 분류의예후측면에서의유효성을알아보고자하였다. 대상및방법 1989년 8월부터 2001년 6월까지 12년동안서울아산병원에서골수검사를시행하여 FAB 진단기준에의해일차성골수이형성증후군으로진단된 218명의성인환자들을대상으로하였다. 이들중남자는 138명 (63.3%), 여자는 80명 (36.7%) 이었고, 연령분포는 15세부터 86세였으며, 연령의중앙값은 56세이었다. 형태학적진단은진단당시의골수소견과혈액학적검사결과를재확인하였다. 이차성골수이형성증후군환자는환자선택에서배제되어대상군에포함되지않았다. 이환자들을 2001년 6월까지후향적으로추적관찰하여생존기간과급성골수성백혈병으로진행여부를확인하였다. 이중세포유전학적검사를시행한 114명은염색체검사결과를함께분석하였다. 모든환자들을 FAB 분류기준 [1] 에따라분류하였고, 다시 WHO 분류기준 [15] 에따라재분

3 한국인 MDS 환자들에대한 WHO 분류의유효성 73 Table 2. Clinical and hematologic features at the diagnosis in patients with myelodysplastic syndrome classified according to the FAB subtypes MDS (all patients) RA RARS RAEB RAEB-t CMML Patients N Median age (range) 57 (15-86) 50 (15-86) 64 (30-81) 60 (20-80) 55 (19-82) 51 (33-74) Sex ratio (M:F) 1.7:1 1.2:1 2.4:1 2.6:1 1.5:1 1.3:1 Neutrophils 10 9 / L median (range) 1.2 ( ) 1.1 ( ) 1.7 ( ) 0.8 ( ) 1.7 ( ) 4.3 ( ) Hemoglobin g/dl median (range) 7.8 ( ) 8.2 ( ) 7.4 ( ) 7.8 ( ) 7.9 ( ) 8.8 ( ) Platelets 10 9 / L median (range) 51 (3-638) 53 (3-638) 94 (14-225) 45 (3-362) 47 (7-473) 84 (12-264) Bone marrow blasts (%) 6.0 ( ) 1.2 ( ) 1.6 ( ) 9.2 ( ) 17.8 ( ) 9.4 ( ) Median survival (mo) Transition to AML N (%) 29 (13) 2 (3) 0 13 (17) 13 (34) 1 (11) Available cytogenetics N Abnormal karyotype N (%) 48 (42) 14 (32) 7 (100) 16 (40) 9 (47) 2 (50) IPSS N (%) [6] Low 8 (7) 7 (16) 1 (3) Intermediate-1 60 (52) 34 (77) 6 (86) 14 (35) 5 (26) 1 (25) Intermediate-2 35 (31) 3 (7) 1 (14) 23 (57) 5 (26) 3 (75) High 11 (10) 2 (5) 9 (48) Abbreviations: MDS, myelodysplastic syndrome; RA, refractory anemia; RARS, refractory anemia with ringed sideroblasts; RAEB, refractory anemia with excess blasts; RAEB-t, refractory anemia with excess blasts in transformation; CMML, chronic myelomonocytic leukemia; AML, acute myelogenous leukemia; IPSS, international prognostic scoring system. FAB RA 78 WHO RA 24 Unclass 2 del (5q) 1 FAB RAEB WHO RAEB-1 42 RAEB-2 51 RARS 17 RCMD 51 RCMD-RS 11 RAEB-t AML 21 RARS 6 CMML 9 9 MDS/MPD 9 Fig. 1. Splitting of FAB subtypes as warranted by the WHO classfication. MDS, myelodysplastic syndrome; RA, refractory anemia; RARS, refractory anemia with ringed sideroblasts; RCMD, refractory cytopenia with multilneage dysplasia; RCMD-RS, refractory cytopenia with multilneage dysplasia with ringed sideroblasts; RAEB, refractory anemia with excess blasts; RAEB-t, refractory anemia with excess blasts in transformation; CMML, chronic myelomonocytic leukemia; 5q, myelodysplastic syndrome with isolated del(5q); AML, acute myelogenous leukemia. 류하였다. 분류된각군과임상소견을비교하여새로운진단기준의유효성을알아보고자하였다. 통계처리는 SPSS ver 10.0을이용하였으며, 생존분석은 Kaplan-Meier 방법을이용하였고, 각군은 Mantel-Cox log rank 법을사용하여비교하였다. 결과이전 FAB 분류기준에따라, 대상환자들은 RA 78명, RARS 17명, RAEB 76명, 변환아세포과다불응성빈혈 (refractory anemia with excess blasts in transformation, RAEB-t) 38명, CMML 9명으로분류되어졌다. 이들의임상적, 혈액학적인특성은 Table 2와같다. 또한세포유전학적검사를실시한 114명에서 International Prognstic Scoring System (IPSS) 정의 [6] 에따라구분했을때, 저위험군 58% (low, 7%; intermediate-1, 51%), 고위험군 42% (intermediate-2, 35%; high, 11%) 로나뉘어졌다. 각군의 IPSS에따른결과는 Table 2와같다. 이들을다시 WHO 분류기준에따라재분류한결과 (Fig. 1),

4 74 손용학 박찬정 서을주외 5 인 Table 3. Clinical and hematologic features at the diagnosis in patients with myelodysplastic syndromes classified according to the WHO subtypes MDS (all patients) RA RARS RCMD RCMD-RS RAEB1 RAEB2 5q unclassified Patients N Median age (range) 56 (15-86) 48 (19-79) 66 (43-81) 50 (15-80) 59 (30-80) 59 (20-79) 56 (19-82) (62-75) Sex ratio (M:F) 1.7:1 0.8:1 2.0:1 1.6:1 2.7:1 3.7:1 1.6:1 F all F Neutrophils 10 9 / L 1.1 ( ) 1.5 ( ) 1.6 ( ) 1.0 ( ) 2.0 ( ) 1.2 ( ) 0.8 ( ) ( ) median (range) Hemoglobin g/dl 7.8 ( ) 8.5 ( ) 6.3 ( ) 8.1 ( ) 7.4 ( ) 8.0 ( ) 7.5 ( ) ( ) median (range) Platelets 10 9 / L 50 (3-638) 38 (6-638) 119 (17-217) 57 (3-307) 93 (14-225) 35 (4-362) 55 (3-317) (35-158) median (range) Bone marrow 4.6 ( ) 0.9 ( ) 2.1 ( ) 1.4 ( ) 1.6 ( ) 7.4 ( ) 12.0 ( ) ( ) blasts (%) Median survival (mo) 23.2 Not reached Transition to AML N (%) 23 (12) (4) 0 2 (5) 19 (37) 0 0 Available cytogenetics N Abnormal karyotype 43 (42) 4 (27) 3 (100) 9 (33) 4 (100) 14 (56) 8 (29) 0 1 (100) N (%) IPSS N (%) [6] Low 8 (8) 2 (13) 4 (15) 1 (4) 1 Intermediate-1 59 (57) 12 (80) 3 (100) 21 (78) 3 (75) 12 (48) 7 (26) 1 Intermediate-2 31 (30) 1 (7) 2 (7) 1 (25) 13 (52) 14 (52) High 5 (5) 5 (18) Abbreviations: MDS, myelodysplastic syndrome; RA, refractory anemia; RARS, refractory anemia with ringed sideroblasts; RCMD, refractory cytopenia with multilneage dysplasia; RCMD-RS, refractory cytopenia with multilineage dysplasia with ringed sideroblasts; RAEB, refractory anemia with excess blasts; 5q, myelodysplastic syndrome with isolated del(5q); AML, acute myelogenous leukemia. 1.0 P= P< cum. survival.6.4 RARS RCMD-RS RA RCMD cum. AML-risk.6.4 RAEB-2.2 RAEB-1 RAEB-2.2 RAEB-1 RCMD Months Fig. 2. Cumulative survival in patients with myelodysplastic syndrome classified according to the WHO classifications. RA, refractory anemia; RARS, refractory anemia with ringed sideroblasts; RCMD, refractory cytopenia with multilneage dysplasia; RCMD- RS, refractory cytopenia with multilineage dysplasia and ringed sideroblasts; RAEB, refractory anemia with excess blasts. RA 24명, RARS 6명, 다계열성이형성을동반한불응성혈구감소증 (refractory cytopenia with multilineage dysplasia, RCMD) 51명, refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS) 11명, RAEB-1 42명, RAEB- 2 51명, MDS with isolated del(5q) 1명, MDS, unclassifiable Months Fig. 3. Cumulative risk of AML transformation in patients with myelodysplastic syndrome classified according to the WHO classfications. RCMD, refractory cytopenia with multilneage dysplasia; RAEB, refractory anemia with excess blasts. 2명이었다. 각군의임상적혈액학적, 세포유전학적특징은 Table 3과같다. 새로운 WHO 분류기준에따라 FAB 분류의 RAEB-t 군 38명중 21명은급성골수성백혈병으로분류되었고, 나머지 17명은골수내아세포가 20% 미만이면서말초혈액세포의아세포가 5% 이상인경우 12명, Auer rod 양성인경우 5명이었으며, 이들은 RAEB-2 군으로포함되었다. 또한 CMML 9명은골수

5 한국인 MDS 환자들에대한 WHO 분류의유효성 75 이형성증후군 / 골수증식성질환 (myelodysplastic syndrome/ myeloproliferative diseases) 으로분류되어제외되었다. 이환자군을 IPSS 정의에따라구분했을때, 103명의환자중저위험군 65% (low, 8%; intermediate-1, 57%), 고위험군 35% (intermediate-2, 30%; high, 5%) 로나뉘어졌다. WHO 분류기준에따라분류하였을때, 각군간의생존기간의차이를알아보았다 (Fig. 2). RA 군과 RCMD 군사이에생존기간에있어서유의한차이를보였다 ( 생존중앙값, 미결정 vs 개월, P=0.020). 그러나, RARS 군과 RCMD-RS 군간 ( 생존중앙값, 51.4 vs. 23.2개월, P=0.577), RCMD 군과 RCMD-RS 군간 ( 생존중앙값, 28.4 vs. 23.2개월, P=0.861) 및 RAEB-1 군과 RAEB-2 군간 ( 생존중앙값, 16.3 vs. 18.0개월, P=0.757) 의생존기간의유의한차이를보이지않았다. 또한 WHO 에의한분류시각군간의급성골수성백혈병으로의진행여부를비교하였다 (Fig. 3). 이경우 RAEB-1 군과 RAEB-2 군사이에서유의한차이를보였다 (5% vs. 37%, P=0.001). 그러나, 다른군간에서는의미있는결과를보이지않았다. 고찰지난 20년동안임상적, 혈액학적으로황금률이되어왔던 FAB 분류기준은서론에서기술했던문제점들로인해, 새로운기준으로변화해야할필요성이요구되어왔다. 그리하여, WHO 소위원회에서새분류기준 [14] 을제안하게되었고, 이에대한검증도필요하게되었다. Germing 등 [17] 은 1,600명을대상으로한후향적인연구를통해, RCMD 군의분리, 골수아세포에따른 RAEB 군의구분, 새로운 del(5q) syndrome의유효성을입증하여 WHO 분류기준이 FAB 분류기준보다예후적으로더우월함을보여주었다. Nosslinger 등 [18] 은 431명을대상으로한연구에서 WHO 분류기준에대한유효성에반하는몇몇증거를보여주었으나 Bennett 등 [19] 은이보고에서이형성의기준을 50% 로정한것과 CMML 군을포함시킨것에대한문제점을지적하였다. 저자들은본연구를통해, 한국인골수이형성증후군환자를대상으로 WHO 분류기준을적용하였을때그유효성을연구하고자하였다. 기존 FAB 분류기준에따른 RA 군은새로운분류기준에따라적혈구계에만이형성이있는 RA 군과두계열이상에서이형성을보이는 RCMD 군으로나뉘게된다. 두군사이에생존기간에있어서의미있는차이를보여주었다. 과립구계와혈소판계의이형성이예후에미치는영향은 Rosati 등 [10] 에의해여러번기술되었다. 이들은적혈구계에만이형성이있는 RA 군과 RCMD 군사이에혈액학적, 세포유전학적소견들의차이를보여주었고, 예후와급성골수성백혈병으로의진행여부도차이가있음을보여주었다. WHO는이것을받아들여, RA 군가운데두계열이상에서이형성을보이는경우 RCMD 라는새로운군을제안하 였다. 본연구는 RA 군과 RCMD 군의예후의차이를보여줌으로써 RCMD 군의필요성을입증하였고, 이는 Germing 등 [17] 의보고와일치하는결과이다. 그러나, 본연구에서급성골수성백혈병으로의진행에차이 (0% vs. 4%) 가없었는데, 이는상대적으로짧은추적기간에기인한것으로추정된다. Gerand 등 [12] 은기존의 RARS군을적혈구계에만이형성을보이는순수철적아구성빈혈 (pure sideroblastic anemia, PSA) 과여러계열에이형성을보이는철적아구성빈혈 (RCMD-RS) 로구분할것을제안하였다. 이후연구 [13] 에서도장기간추적관찰한결과예후적인차이가있어서, WHO는순수철적아구성빈혈만을 RARS 군으로인정하였고, 다계열성이형성을보이는철적아구성빈혈을 RCMD-RS 군으로구별하였다. 그러나본연구에서는두군사이에생존기간및급성골수성백혈병으로의진행에있어서유의한차이가나타나지않았고, 그원인으로는 RARS 군의대상수가적은것이이유로추정된다. 그리고, RCMD-RS 군과 RCMD 군사이에생존기간이유사하며 (28.4개월 vs 개월 ), 이는 Germing 등의보고 [17] 에서보여준결과와같다. 이전부터골수아세포가 MDS의가장중요한단일예후인자로알려져왔고, 특히 RAEB 군에서골수아세포의기준범위 (5-20%) 가상당히넓어서, 예후적으로차이가있는것이알려져왔다 [3, 5, 6]. WHO에서는이러한보고들을받아들여, RAEB 군을 10% 를기준으로하여골수아세포의정도에따라 RAEB-1 군과 RAEB-2 군으로구분하였다. 본연구에서 RAEB-1 군과 RAEB- 2 군을비교하였을때, 두군간에급성골수성백혈병의진행여부에있어서의미있는차이를보여주었다. 그러나, 두군간에생존기간의차이는없었다. 이는급성골수성백혈병으로진행한경우, 항암화학요법또는골수이식등과같이집중적치료로인해생존기간이증가된것이원인인것으로사료된다. WHO에서새로제안한 5q 염색체결실을동반한골수이형성증후군 [20, 21] 은 RA 군과다른여러특징을보여주고있다. 거대세포성빈혈, 정상또는증가된혈소판수, 혈소판분화세포의소분엽등을특징으로하며, RA 군에비해예후가좋은것으로알려져있다. Germing 등 [17] 의연구에서도같은결과를보여주었으나, 본연구에서는 1예뿐이라그의미를부여하기는어려운것으로생각된다. 결론적으로새로운 WHO 분류기준이예후적인측면에서유효성이있음을보여주므로 MDS 진단시 WHO 분류를사용할것을권장한다. 그러나, 이연구에있어서, 몇가지한계점이있다. IPSS와같은예후적점수시스템은새로운 WHO 분류기준을적용했을때, 새로구분된군사이에서뚜렷한차이를보여주지못했다. 또한상대적으로적은환자수로인해몇몇군에서통계적으로의미를부여하지못한경우가있었고, 급성골수성백혈병진행여부에있어서도짧은기간추적관찰로인해상대적으로예후가좋은것으로생각되는아군간에비교가불가능하였다.

6 76 손용학 박찬정 서을주외 5 인 요약배경 : WHO는 1999년골수이형성증후군에대한기존의 FAB 분류기준에수정을가하여새로운분류기준을제안하였다. 본연구는예후적인면에서새로운분류기준의유효성을알아보고자하였다. 방법 : 1989년 8월부터 2001년 6월까지울산의대서울아산병원에서 FAB 기준에따라골수이형성증후군으로진단된 218명을대상으로하였다. 이들의진단당시의세포형태적, 임상적, 세포유전학적자료를수집하였고, 추적관찰후의임상적결과도후향적으로확인하였다. 새로운 WHO 분류기준에따라재분류하여예후적인측면을비교하였다. 결과 : 기존의 FAB 분류기준에따라, 218명의환자들은각각 RA 78명, RARS 17명, RAEB 76명, RAEB-t 38명, CMML 9명이었다. WHO 분류기준에따라재분류한결과 RA 24명, RARS 6명, RCMD 51명, RCMD-RS 11명, RAEB-1 42명, RAEB-2 51명, del(5q) syndrome 1명과 unclassifiable 2명이었다. RAEB-t 21명은급성골수성백혈병으로, CMML 9명은골수이형성증후군 / 골수증식성질환으로분류되어골수이형성증후군에서제외되었다. 예후적인유효성을살펴본결과, RA 군과 RCMD 군사이에생존기간에있어서유의한차이가있었다 ( 생존중앙값, 미결정 vs. 28.4개월, P=0.020). RAEB-1 군과 RAEB-2 군사이에급성골수성백혈병진행정도 (5% vs. 37%, P=0.001) 에유의한차이를보였다. 결론 : 새 WHO 분류기준이예후적인면에있어서유효성이있으므로골수이형성증후군진단시 WHO 분류를사용할것을권장한다. 참고문헌 1. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DG, Gralnick HR, et al. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 1982; 51: Kerkhofs H, Hermans J, Haak HL, Leeksma CH. Utility of the FAB classification for myelodysplastic syndrome: investigation of prognostic factors in 237 cases. Br J Haematol 1987: 65: Sanz GF, Sanz MA, Vallespi T, Canizo MC, Torrabadella M, Garcia S, et al. Two regression models and a scoring system for predicting survival and planning treatment in myelodysplastic syndromes: a multivariate analysis of prognostic factors in 370 patients. Blood 1989; 74: Aul C, Gattermann N, Heyll A, Germing U, Derigs G, Schneider W. Primary myelodysplastic syndromes: analysis of prognostic factors in 235 patients and proposals for an improved scoring system. Leukemia 1992; 6: Morel P, Hebbar M, Lai JL, Duhamel A, Preudhomme C, Wattel E, et al. Cytogenetic analysis has strong independent prognostic value in de novo myelodysplastic syndromes and can be incorporated in a new scoring system: a report on 408 cases. Leukemia 1993; 7: Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, et al. International Scoring System for evaluating prognosis in myelodysplastic syndromes. Blood 1997; 89: Verhoef GE, Pittaluga S, De Wolf-Peeters C, Boogaerts MA. FAB classification of myelodysplastic syndromes: merits and controversies. Ann Hematol 1995; 71: Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick H, et al. The chronic myeloid leukaemias: guidelines for distinguishing chronic granulocytic, atypical chronic myeloid, and chronic myelomonocytic leukaemia. Proposals by the French-American- British Cooperative Leukaemia Group. Br J Haematol 1994; 87: Germing U, Gattermann N, Minning H, Heyll A, Aul C. Problems in the classification of CMML-dysplastic versus proliferative type. Leuk Res 1998; 22: Rosati S, Mick R, Xu F, Stonys E, Le Beau MM, Larson R, et al. Refractory cytopenia with multilineage dysplasia: further characterization of an unclassifiable myelodysplastic syndrome. Leukemia 1996; 10: Matsuda A, Jinnai I, Yagasaki F, Kusumoto S, Minamihisamatsu M, Honda S, et al. Refractory anemia with severe dysplasia: clinical significance of morphological features in refractory anemia. Leukemia 1998; 12: Garand R, Gardais J, Bizet M, Bremond JL, Accard F, Callat MP, et al. Heterogeneity of acquired idiopathic sideroblastic anaemia (AISA). Leuk Res 1992; 16: Germing U, Gattermann N, Aivado M, Hildebrandt B, Aul C. Two types of acquired idiopathic sideroblastic anaemia: a time-tested distinction. Br J Haematol 2000; 108: Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, et al. The World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee Meeting - Airline House, Virginia, November J Clin Oncol 1999; 17: Jaffe ES, Harris NL, et al. eds. World Health Organization of Tumours: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissue. Lyon, France: IARC press, 2000: Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 2002; 100: Germing U, Gattermann N, Strupp C, Aivado M, Aul C. Validation of the WHO proposals for a new classification of primary myelodysplastic syndromes: a retrospective analysis of 1600 patients. Leuk

7 한국인 MDS 환자들에대한 WHO 분류의유효성 77 Res 2000; 24: Nosslinger T, Reisner R, Koller E, Gruner H, Tuchler H, Nowotny H, et al. Myelodysplastic syndromes, from French-American-British to World Health Organization: comparison of classifications on 431 unselected patients from a single institution. Blood 2001; 98: Bennett JM, Brunning RD, Vardiman JW. Myelodysplastic syndromes: from French-American-British to World Health Organization: a commentary. Blood 2002; 99: Boultwood J, Lewis S, Wainscoat JS. The 5q- syndrome. Blood 1994; 84: Heaney ML and Golde DW. Myelodysplasia. N Eng J Med 1999; 340:

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7.Æ¯Áýb71ÎÀ¯È« š 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 : jwcheong70@yumc.yonsei.ac.kr minbrmmd@yumc.yonsei.ac.kr