Korean J Lab Med 2010;30:231-8 DOI /kjlm Original Article Diagnostic Hematology Clinical Importance of Morphological Multilineage

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1 Korean J Lab Med 2010;30:231-8 DOI /kjlm Original Article Diagnostic Hematology Clinical Importance of Morphological Multilineage Dysplasia in Acute Myeloid Leukemia with Myelodysplasia Related Changes Sang Hyuk Park, M.D., Hyun-Sook Chi, M.D., Seo-Jin Park, M.D., Seongsoo Jang, M.D., and Chan-Jeoung Park, M.D. Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea Background : AML with myelodysplasia related changes (AML MRC) is known to show a poor prognosis compared with de novo AML, but controversies exist about the prognostic impact of multilineage dysplasia (MLD) among MRC. We investigated the prognostic impact of MLD in AML MRC. Methods : A total of 357 patients newly diagnosed as AML at Asan Medical Center from January 2001 to December 2005 were analyzed. They were diagnosed and classified as AML with recurrent genetic abnormalities, AML MRC, and AML not otherwise specified (AML NOS). Prognostic markers including overall survival (OS) and event free survival (EFS) were obtained through retrospective analysis of electronic medical records. Results : AML MRC patients showed a lower complete remission () rate (44.7% vs. 64.9%, P= 02) and shorter OS (297 vs. 561 days, P=04) and EFS (229 vs. 374 days, P=04) than AML NOS patients. Patients with MLD among AML MRC also showed a lower rate (37.7%, P=01) and shorter OS (351 days, P=36) and EFS (242 days, P=76) than AML NOS patients. However, among AML MRC patients, there were no differences in OS, EFS and between patients with and without MLD. Conclusions : AML MRC patients showed a lower rate and shorter OS and EFS than AML NOS patients. AML MRC patients with MLD showed similar results and their prognosis was not different from those without MLD. MLD findings among AML MRC could be an independent poor prognostic factor in de novo AML. (Korean J Lab Med 2010;30:231-8) Key Words : Prognosis, Multilineage, Dysplasia, AML, Myelodysplasia, Related, Changes 서 Received : November 9, 2009 Manuscript No : KJLM Revision received : March 23, 2010 Accepted : April 30, 2010 Corresponding author : Hyun-Sook Chi, M.D. Department of Laboratory Medicine, Asan Medical Center and University of Ulsan College of Medicine, Pungnap 2-dong, Songpa-gu, Seoul , Korea Tel : , Fax : hschi@amc.seoul.kr ISSN 론 The Korean Society for Laboratory Medicine 골수이형성관련급성골수성백혈병 (AML with myelodysplasia related changes, AML MRC) 은골수이형성증후군 (MDS) 의병력또는 MDS 관련세포유전학적이상또는 2가지이상의계열에서 50% 이상의이형성이관찰되는형태학적다계열이형성 (multilineage dysplasia, MLD) 이있는환자에서말초혈액또는골수천자의모세포분율이 20% 를넘고세포독성치료의병력이나 AML 관련반복염색체이상 (AML with recurrent genetic abnormalities, AML RGA) 이없을때진단하게된다. AML RGA에는 t(8;21)(q22;q22), inv(16)(p13.1q22)/t(16;16)(p13.1; q22), t(15;17)(q22;q12), t(9;11)(p22;q23), t(6;9)(p23;q34), inv(3)(q21q26.2)/t(3;3)(q21;q26.2), t(1;22)(p13;q13) 등이속하며 MDS 관련세포유전학적이상에는 AML RGA에해당하지않는염색체이상이 3개를초과하여존재할경우이거나또는 5,7,9,11,13번염색체의장완결실또는 12번염색체의단완결실및여러가지의균형전좌 (balanced translocation) 가속한다 [1]. AML MRC는심한전혈구감소증을잘보이며고령의환자에서흔하고 CD7, CD56 이상표현이흔하다고알려져있으며완전관해율이다른 AML에비해낮고고위험군핵형이상이잘동반되어예후가좋지않다고알려져있다 [1, 2]. MLD를동반한 AML MRC의경우에도일반적으로는좋지않은예후를보이지만고위험군핵형이상의역할을배제한 MLD의독립적인예후인자로써의역할에대해서는논란이있어왔다. 이에저자들은단일기관에서새로이진단된 357명의 AML 환자를대상으 231

2 232 Korean J Lab Med 2010;30:231-8 로 AML MRC 환자에서 MLD의임상적의의에대해분석하고자하였다. 대상및방법 비교하였다. MLD는 2008년 WHO 분류에따라적어도 2개이상의계열에서 50% 이상의이형성이관찰되는경우로정의하였으며 [1] 추가적으로 MLD를동반한 AML MRC 환자와 MLD를동반하지않은 AML MRC 환자에대해같은비교를시행하였다. 1. 대상환자및분류, 치료방법 2001년 1월부터 2005년 12 월까지울산의대서울아산병원에서 AML로처음진단받은 357명의환자들을대상으로하였다. 모든환자들은 2008년개정된 WHO분류에의해 AML RGA, AML MRC, 미분류 AML (AML not otherwise specified, AML NOS) 로분류하였으며 [1] AML M3 (French American British, FAB 분류 ) 를제외한환자들은진단후 cytarabine mg/m 2 씩제1 일부터 7일간계속정주하고 idarubicin 12 mg/m 2 을제1 일부터 3일간매일정주하는 1차관해유도치료를받았고치료시작 14일째시행한골수검사에서모세포분율이 5% 를넘는경우동일용량으로 cytarabine은 5일, idarubicin은 2일간투여하는 2차관해유도치료를받았다. 완전관해는골수의세포밀도가 25% 이상을나타내고모세포분율이 5% 미만인경우로하였고완전관해에도달한환자들은 cytarabine과 anthracycline으로이루어진 3회의공고요법을시행받았다. AML M3 환자들은 all-transretinoic acid에기초한항암요법을시행받았으며 HLA가일치하는공여자가있는젊은환자의경우에는 1차완전관해상태에서골수이식을시행받았다. 4. AML MRC 또는 MLD를동반한 AML MRC 환자와이외의환자와의예후비교 MRC 및 MLD가예후에미치는영향을분석하기위해 AML MRC 환자또는 MLD를동반한 AML MRC 환자와이외의환자로나누어각군간의완전관해율, 사망률, 전체생존기간및무질병생존기간을비교하였다. 추가적으로이외의환자중 t(8;21) (q22;q22), inv(16)(p13.1q22)/t(16;16)(p13.1;q22), t(15;17)(q22; q12) 등의좋은예후를보이는세포유전학적이상을보이는환자를제외한후같은비교를시행하였다. 5. 여러변수의예후에미치는영향에대한다변량분석전체생존기간, 무질병생존기간, 완전관해율, 재발률에미치는여러변수의영향을분석하기위해연령, 백혈구수, 모세포분율, 세포유전학적이상, MRC 및 MLD의존재, FLT3 돌연변이등의변수에대한다변량분석을시행하였다. 6. 통계처리 2. 전체환자및 AML MRC 환자의임상적특성및예후모든환자들의성별, 연령, FAB 분류, 진단시총혈구수, 모세포분율, 유세포검사결과, 세포유전학적이상유무, FLT3 ITD (Fms-related tyrosine kinase 3 internal tandem duplications), FLT3 D835 돌연변이유무, 추적검사중완전관해, 재발및사망유무에대해의무기록을후향적으로참고하여조사하였다. 예후분석을위해전체생존기간및무질병생존기간을구하였고언급된변수들에대해 AML MRC 환자와 AML NOS 환자및 AML RGA 환자의비교를시행하였다. 3. AML MRC 환자의소분류별예후비교 AML MRC 환자를이전 MDS 병력이있는경우, MDS 연관세포유전학적이상의존재, MLD를동반한경우로나누어각군간의완전관해율, 사망률, 전체생존기간및무질병생존기간을 성별, 완전관해율, 재발률, 사망률, FLT3 돌연변이여부의비교에는 Chi square test를시행하였고연령, 총혈구수, 모세포분율의비교에는 Student t test를시행하였다. 전체생존기간및무질병생존기간의비교에는 Kaplan-Meier 및 log-rank test를시행하였다. 예후에미치는변수에대한다변량분석에는이분형로지스틱분석및 Cox s proportional hazard model 을사용하여상대위험도 (hazard ratio) 를구하였다. 모든분석에서는양측검정을시행하여 P값을얻었고 P값이 5 미만일때통계적으로유의하다고판정하였다. 결과 1. 전체환자및 AML MRC 환자의임상적특성및예후전체 357명의환자중 AML RGA, AML MRC, AML NOS는각각 115명 (32.2%), 94명 (26.3%), 148명 (41.5%) 이었다. AML

3 Park SH, et al., Clinical Importance of MLD in AML MRC 233 MRC 환자가 AML NOS 환자에비해헤모글로빈이낮은경향을보였고 (8.5 g/dl vs. 9.0 g/dl, P=9) 백혈구수 (5,100/mL vs. 10,800/mL, P<01) 및모세포분율 (50.5% vs. 66.1%, P< 01) 이낮았으며 FLT3 ITD 돌연변이가적었고 (5.1% vs. 17.4%, P=11) 완전관해율이낮았으며 (44.7% vs. 64.9%, P=02), 사망률이높은경향을보였다 (76.6% vs. 64.9%, P=54). 전체생존기간및무질병생존기간의비교에서 AML MRC 환자가 AML NOS 환자에비해전체생존기간 (297일 vs. 561일, P= 04) 및무질병생존기간 (229일 vs. 374일, P=04) 이짧았고 AML RGA 환자와의비교에서도같은결과를보였다 (P< 01) (Fig. 1, Table 1). 2. AML MRC 환자군의소분류별예후비교전체 94명의 AML MRC 환자중이전 MDS 병력을보인환자가 9명 (9.6%), MDS 연관세포유전학적이상을보인환자가 32명 (34.0%), MLD를동반한환자가 53명 (56.4%) 이었다. 전체생존기간및무질병생존기간은세군모두유의한차이가없었다 (Fig. 2). MLD를동반한환자에서 MDS 연관세포유전학적이상을보인환자보다완전관해율이낮은경향을보였으며 (37.7% vs. 59.4%, P=52) 이전 MDS 병력을보인환자보다사망률이높았다 (81.1% vs. 22.2%, P<01) (Table 2). 그러나 MLD 를동반한 AML MRC 환자와 MLD를동반하지않은 AML MRC Overall survival RGA MRC NOS RGA-censored MRC-censored NOS-censored Event free survival RGA MRC NOS RGA-censored MRC-censored NOS-censored P<01 P=04 P<01 P=04 0 1,000 2,000 3,000 Survival (days) 0 1,000 2,000 3,000 Event free survival (days) Fig. 1. Comparison of overall survival and event free survival in 357 patients among 3 AML groups according to revised 2008 WHO classification. Abbreviations: RGA, recurrent genetic abnormalities; MRC, myelodysplasia related changes; NOS, not otherwise specified. Table 1. Clinical characteristics and prognosis in 3 AML groups Clinical variables AML RGA (N=115) AML NOS (N=148) AML MRC (N=94) P value* Age, median (range) 42 (2-80) 45 (1-82) 53 (2-79) Hb (g/dl), median (range) 8.8 ( ) 9.0 ( ) 8.5 ( ) 9 WBC ( 1,000 /ml), median (range) 8.4 (-239.4) 1 ( ) 5.1 ( ) <01 Platelet ( 1,000 /ml), median (range) 44.0 (5.0-51) 57.0 ( ) 42.5 ( ) Blast (%), median (range) 66.8 (2-96.2) 66.1 ( ) 50.5 ( ) <01 FLT3 ITD mutation 10% 17.4% 5.1% 11 FLT3 D835 mutation 14.7% 7.6% 5.0% % 64.9% 44.7% 02 Relapse 26.1% 3% 29.8% Death 26.1% 64.9% 76.6% 54 OS (days), median 1,455.0, P< EFS (days), median 1,294.0, P< *P value, NOS compared with MRC; P value compared with MRC. Abbreviations: RGA, recurrent genetic abnormalities; NOS, not otherwise specified; MRC, myelodysplasia related changes; WBC, white blood cells; FLT3, Fms-related tyrosine kinase 3; ITD, internal tandem duplication;, complete remission; OS, overall survival; EFS, event free survival.

4 234 Korean J Lab Med 2010;30:231-8 Overall survival Prior MDS history MDS related cytogenetic abnormality MLD Prior MDS history-censored MDS related cytogenetic abnormality-censored MLD-censored Event free survival Prior MDS history MDS related cytogenetic abnormality MLD Prior MDS history-censored MDS related cytogenetic abnormality-censored MLD-censored P=0.712 P=0.749 P=0.504 P= ,000 2,000 3,000 Survival (days) ,000 1,500 2,000 2,500 3,000 Event free survival (days) Fig. 2. Comparison of overall survival and event free survival of AML MRC patients among 3 subgroups. Abbreviation: MLD, multilineage dysplasia. Table 2. Comparison of OS, EFS, and death rate among subgroups of AML MRC Type and description OS Median (days) Prior MDS history (N=9) % 22.2% (P value compared with MLD) P =0.712 P =0.504 P =00 P <01 MDS related cytogenetic abnormality (N=32) % 84.3% (P value compared with MLD) P =0.749 P =0.391 P =52 P =0.704 MLD (N=53) % 81.1% Abbreviations: OS, overall survival; EFS, event free survival;, complete remission; MRC, myelodysplasia related changes; MLD, multilineage dysplasia. EFS Death 환자간의비교에서는완전관해율, 사망률, 전체생존기간및무질병생존기간모두유의한차이가없었다 (Table 3). 3. AML MRC 또는 MLD를동반한 AML MRC 환자와이외의환자와의예후비교 AML MRC 환자가 MRC 이외의 AML 환자에비해전체생존기간 (297일 vs. 994일, P<01) 및무질병생존기간 (229일 vs. 579일, P<01) 이짧았고완전관해율 (44.7% vs. 71.1%, P< 01) 이낮았으며사망률 (76.6% vs. 47.9%, P<01) 도높았다. 또한좋은예후를보이는세포유전학적이상을제외한 MRC 이외의 AML 환자에비해서도전체생존기간 (297일 vs. 556일, P=04) 및무질병생존기간 (229일 vs. 373일, P=07) 이짧았고완전관해율 (44.7% vs. 65.4%, P=01) 이낮았으며사망률 (76.6% vs. 64.7%, P=49) 이높았다 (Table 4). MLD를동반한 AML MRC 환자가 MLD 이외의 AML 환자에비해높은연령 (56세 vs. 44세, P=06) 및낮은모세포분율 (42.0% Table 3. Comparison of OS, EFS, and death rate between MLD and other MRC Median (days) OS EFS Death MLD % 81.1% (P value compared P=0.342 P=0.154 P=0.124 P=38 with other MRC) Other MRC % 70.7% Abbreviations: OS, overall survival; EFS, event free survival;, complete remission; MLD, multilineage dysplasia; MRC, myelodysplasia related changes. vs. 66.3%, P<01) 을보였으며전체생존기간 (351일 vs. 858 일, P=02) 및무질병생존기간 (242일 vs. 463일, P=11) 이짧았고 (Fig. 3) 완전관해율 (37.7% vs. 68,8%, P<01) 이낮았으며사망률 (81.1% vs. 5%, P<01) 이높았고이는 AML MRC 환자와동일한결과였다. 좋은예후를보이는세포유전학적이상을제외한 MLD 이외의 AML 환자에비해서도완전관해율 (37.7% vs. 62.9%, P=01) 이낮았으며사망률 (81.1% vs.

5 Park SH, et al., Clinical Importance of MLD in AML MRC 235 Overall survival Other AML MLD Other AML-censored MLD-censored Event free survival Other AML MLD Other AML-censored MLD-censored P=02 P=11 0 1,000 2,000 3,000 Survival (days) 0 1,000 2,000 3,000 Event free survival (days) Fig. 3. Comparison of overall survival and event free survival of AML MLD patients compared with other AML. Abbreviation: MLD, multilineage dysplasia. Table 4. Comparison of OS, EFS, and death rate between AML MRC and other AML Median (days) Other AML (N=263) % 47.9% (P value compared with AML MRC) P <01 P <01 P <01 P <01 Other AML, good prognostic cytogenetics excluded (N=156) % 64.7% (P value compared with AML MRC) P =04 P =07 P =01 P =49 AML MRC (N=94) % 76.6% Abbreviations: OS, overall survival; EFS, event free survival;, complete remission; MRC, myelodysplasia related changes. OS EFS Death Table 5. Comparison of OS, EFS, and death rate between AML MLD and other AML Type and description Median (days) Other AML (N=304) % 5% (P value compared with MLD) P =02 P =11 P <01 P <01 Other AML, good prognostic cytogenetics excluded (N=197) % 66.0% (P value compared with MLD) P =0.125 P =74 P =01 P =34 AML NOS (N=148) % 64.9% (P value compared with MLD) P =36 P =76 P =01 P =28 MLD (N=53) % 81.1% Abbreviations: OS, overall survival; EFS, event free survival;, complete remission; MLD, multilineage dysplasia. OS EFS Death 66.0%, P=34) 이높았으나전체생존기간 (351일 vs. 517일, P=0.125) 및무질병생존기간 (242일 vs. 309일, P=74) 은유의한차이가없었다. AML NOS 환자에비해서도전체생존기간 (351일 vs. 561일, P=36) 이짧았고무질병생존기간 (242일 vs. 374일, P=76) 도짧은경향을보였으며완전관해율 (37.7% vs. 64.9%, P=01) 이낮았고사망률 (81.1% vs. 64.9%, P= 28) 은높았다 (Table 5). 4. 여러변수의예후에미치는영향에대한다변량분석 60세이상인경우전체생존기간및무질병생존기간, 완전관해율의나쁜예후인자였으며, 모세포분율이 60% 이하인경우무질

6 236 Korean J Lab Med 2010;30:231-8 Table 6. Factors associated with OS, EFS, and relapse rate Variables HR (95% CI) OS P Adverse value effect HR (95% CI) EFS P Adverse value effect HR (95% CI) P Adverse value effect HR (95% CI) Relapse P Adverse value effect Age > <01 > > ( 60 vs. >60) ( ) ( ) (6-1) ( ) WBC ( 20,000/mL ,000 vs. >20,000/mL) ( ) (7-1.80) (2-1.67) ( ) /ml Blasts % ( 60% vs. >60%) (6-1.20) ( ) (5-3.01) (3-1.42) MRC (Yes vs. No) Yes Yes 8 30 Yes ( ) (8-3.20) (9-8) ( ) MLD (Yes vs. No) 1.87 <01 Yes Yes 5 <01 Yes ( ) ( ) (0.13-6) ( ) Abbreviations: OS, overall survival; EFS, event free survival;, complete remission; HR, hazard ratio; WBC, white blood cells; MRC, myelodysplasia related changes; MLD, multilineage dysplasia. 병생존기간에서나쁜예후인자로확인되었다. MRC의존재가전체생존기간및무질병생존기간, 완전관해율의나쁜예후인자였으며 MLD의존재도 MRC와동일한결과를보였다 (Table 6). 고찰이전의보고들을통해 AML에서예후에관련된인자에는환자의연령, FAB 분류, 혼합성면역표현형, 염색체이상, 미세잔류세포의존재등이있다고알려져있었으며 [3-6], 그외형태학적이형성및세포유전학적이상의임상적의미가구체화되면서 2001년 WHO 분류에서 MLD를보이고나쁜예후를보인다고알려진염색체이상을동반하는 AML을 AML MLD라명명하였다 [7]. AML MLD 환자의경우여러연구에서다른 AML에비하여나쁜예후를보인다고알려져왔지만이는나쁜예후를보인다고알려진염색체이상이빈번한빈도로관찰되기때문이며 MLD 자체는독립적인예후인자가되지못한다는상반된견해도있었다 [8-11]. 또한삼계열이형성 (trilineage dysplasia) 이관찰되는경우에도골수의모세포분율이낮고 AML M4 및 M6 의높은빈도를보임과동시에완전관해율이낮고관해유지기간및전체생존기간이짧아불량한예후를보였다는보고들이있는반면예후와무관하였다는보고들도있어 MLD의존재가예후에미치는영향에대해논란이있었다 [12-17]. 2008년개정된 WHO 분류에는 AML MLD에이전의세포독성치료병력및 MDS 연관세포유전학적이상이있는경우를포함하여 AML MRC로재분류하였고 [1] 최근 100명의 AML 환자를대상으로한 AML MRC 환자의임상적특성에대한연구가발표되었는데이에따르면 AML NOS 환자에비해높은발병연령및헤모 글로빈수치가낮고전체생존기간및무진행생존기간이짧았으며낮은완전관해율을보여예후가나빴고 MLD만을동반한 AML MRC 환자에서도비슷한결과를보여 MRC 및 MLD 의존재가나쁜예후와관련이있다고보고하였다 [18]. 본연구에서 AML MRC는 26.3% 의환자에서발견되었고이는 AML MLD의빈도를 24-38% 로보고한이전결과와유사하였으나최근보고된 AML MRC의빈도인 48% 보다는낮았다 [10, 18-20]. AML MRC 환자에서 AML NOS 환자에비해낮은모세포분율및백혈구수를보였는데삼계열이형성을동반한 AML 환자에서그렇지않은환자에비해유의하게낮은모세포분율및백혈구수를보인다고한이전보고와유사한결과였다 [12-15]. 헤모글로빈은 AML MRC 환자에서통계적으로유의하지는않지만낮은경향을보여최근 AML MRC 환자에서 AML NOS 환자에비해유의하게낮은헤모글로빈수치를보였다는보고와비슷하였다 [18]. 또한본연구에서 AML MRC 환자가 AML NOS 환자에비해유의하게낮은 FLT3 ITD 돌연변이, 유의하게짧은전체생존기간, 무질병생존기간및낮은완전관해율을보인것은최근보고와일치하였고 [18], MRC 이외의 AML 환자와의비교와좋은예후를보이는것으로알려진세포유전학적이상의영향을배제후의비교에서도같은결과를보인것은 AML MRC 환자에서예후가나쁜것으로알려져있는 FLT3 ITD 돌연변이의빈도가낮았다는것을감안하였을때 AML MRC 환자의경우그자체만으로도불량한예후를보임을뒷받침하는결과이다 [1]. 본연구에서 MRC로정의된세군간의비교에서는전체생존기간및무질병생존기간모두유의한차이가없었는데이는이전 MDS 병력이있었던환자와 MLD가있는환자의비교에서생존

7 Park SH, et al., Clinical Importance of MLD in AML MRC 237 기간의차이가없었다는이전보고와일치한다 [8]. 또한 MLD를동반한 AML MRC 환자에서 MDS 연관세포유전학적이상을보인환자보다유의하지는않지만낮은완전관해율을보인것과이전 MDS 병력이있었던환자보다높은사망률을보인것, MLD를동반하지않은 AML 환자에비해짧은전체생존기간및무질병생존기간, 낮은완전관해율, 높은사망률을보인것, AML NOS 환자와의비교에서도무질병생존기간이유의한차이가없었던것을제외하고같은결과를보인것은 MLD를동반한 AML MRC 환자에서 MLD를동반하지않은 AML 및 AML NOS 환자보다낮은생존율을보였다는이전보고와일치하였고 MLD의존재가불량한예후인자임을뒷받침하는결과이다 [8, 10]. 그러나좋은예후를보이는세포유전학적이상을보인환자군을배제후의비교에서는낮은완전관해율및높은사망률을보였지만생존기간은유의한차이가없었는데이는 MLD를동반한 AML MRC 환자가좋은예후를보이는세포유전학적이상을제외한 MLD 이외의 AML 환자와생존기간및무질병생존기간의유의한차이가없었던이전보고와일치하여 MLD의예후인자로써의역할이 MRC에비해모든변수에서일치하지는않는다는것을보여주는결과이다 [11]. 여러연구에서실시한임상적변수들의생존기간에대한다변량분석에서 60세이상의연령, 나쁜예후를보이는세포유전학적이상은공통적으로나쁜예후인자로제시되고있었으나 MLD 의경우예후인자로써논란이있었다. 본연구에서는 60세이상인경우전체생존기간및무질병생존기간, 완전관해율의나쁜예후인자로나타나이전보고들과일치하였고모세포분율이 60% 이하인경우무질병생존기간의나쁜예후인자로나타났으며 MRC 가전체생존기간및무질병생존기간, 완전관해율의나쁜예후인자로나타났고 MLD의경우에도 MRC와같은결과를보였는데이는 MRC 및 MLD를나쁜예후인자로보고하였던최근보고 [18] 와일치하는결과였으며 MLD를나쁜예후인자로인정하지않았던이전보고들과상반된결과였다 [9-11]. 이는비록 MLD 를동반한 AML MRC 환자가좋은예후를보이는세포유전학적이상을제외한 MLD 이외의 AML 환자와의비교에서는생존기간의유의한차이가없었지만 MLD의독립적인예후인자로써의가능성을제시해주는결과이다. 결론적으로, 본연구에서 AML MRC 환자가 AML NOS 환자에비해낮은완전관해율과짧은전체생존기간및무질병생존기간을보였고 MLD를동반한 AML MRC 환자도유사한결과를보였으며 MLD를동반하지않은 AML MRC 환자와비교하였을때예후의차이가없어새로이발생한 AML에서 AML MRC 중 MLD 의존재가독립적인나쁜예후인자가될수있다고사료된다. 요약배경 : 골수이형성관련급성골수성백혈병 (AML with myelodysplasia related changes, AML MRC) 은새로이발생한 AML에비해예후가나쁘다는것이잘알려져있으나 MRC 중다계열이형성 (multilineage dysplasia, MLD) 이예후에미치는영향에대해서는논란이있어왔다. 이에저자들은 AML MRC 에서 MLD의예후적의미에대해평가하였다. 방법 : 2001년 1월부터 2005년 12 월까지서울아산병원에서 AML로처음진단받은 357명의환자들을대상으로하였다. 모든환자들은 AML with recurrent genetic abnormalities (RGA), AML MRC, AML not otherwise specified (NOS) 로분류하여진단되었으며전체생존기간, 무질병생존기간을포함한예후인자들은전자의무기록을후향적으로분석하여얻었다. 결과 : AML MRC 환자는 AML NOS 환자에비해완전관해율 (44.7% vs. 64.9%, P=02) 이낮았고전체생존기간 (297일 vs. 561일, P=04) 및무질병생존기간 (229일 vs. 374일, P= 04) 이짧았다. MLD를동반한 AML MRC 환자도 AML NOS 환자에비해완전관해율 (37.7%, P=01) 이낮았고전체생존기간 (351일, P=36) 이짧았으며무질병생존기간 (242일, P= 76) 도짧은경향을보였다. 그러나 MLD를동반한 AML MRC 환자와 MLD를동반하지않은 AML MRC 환자간에는생존기간및완전관해율의유의한차이가없었다. 결론 : AML MRC 환자는 AML NOS 환자에비해완전관해율이낮았고전체생존기간및무질병생존기간이짧았다. MLD 를동반한 AML MRC 환자도유사한결과를보였고 MLD를동반하지않은 AML MRC 환자와비교하였을때예후의차이가없어새로이발생한 AML에서 AML MRC 중 MLD의존재가독립적인나쁜예후인자가될수있다고사료된다. 참고문헌 1. Swerdlow SH, Campo E, et al. eds. WHO classification of tumours of hematopoietic and lymphoid tissues. 4th ed. Lyon: IARC Press, Gahn B, Haase D, Unterhalt M, Drescher M, Schoch C, Fonatsch C, et al. De novo AML with dysplastic hematopoiesis: cytogenetic and prognostic significance. Leukemia 1996;10: Cunningham I, Gee TS, Reich LM, Kempin SJ, Naval AN, Clarkson BD. Acute promyelocytic leukemia: treatment results during a decade at Memorial Hospital. Blood 1989;73:

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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