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1 대한수혈학회지 : 제 25 권제 2 호, 2014 The Korean Journal of Blood Transfusion Vol. 25, No. 2, , August 2014 ISSN Original Article 백혈구증다증환자에서치료적백혈구성분채집술의임상적효과및안전성 이세나 1 ㆍ공정희 1 ㆍ엄현석 2 ㆍ이혜원 2 ㆍ박현진 3 ㆍ손지연 1 ㆍ공선영 1 국립암센터진단검사센터진단검사의학과 1, 특수암센터혈액종양클리닉 2, 소아암센터 3 Clinical Effects and Safety of Therapeutic Leukapheresis in Hyperleukocytosis Se-Na Lee 1, Jung Hee Kong 1, Hyeon Seok Eom 2, Hyewon Lee 2, Hyeon Jin Park 3, Ji Yeon Sohn 1, Sun-Young Kong 1 Department of Laboratory Medicine, Center for Diagnostic Oncology 1, Hematology-Oncology Clinic, Center for Specific Organs 2, Center for Pediatric Oncology 3, National Cancer Center, Goyang, Korea Background: Therapeutic leukapheresis is the cytoreduction procedure performed before chemotherapy in patients with hyperleukocytosis for prevention of complication. However, there have been clinical concerns about bleeding tendency due to anticoagulant used during the procedure. The aim of our study was to compare the clinical characteristics and hematological parameters before and after therapeutic leukapheresis in order to evaluate its effect on bleeding tendency and to provide a guideline for treatment strategy. Methods: The clinical data for 39 procedures of therapeutic leukapheresis performed on 17 patients with hyperleukocytosis from May 2005 to October 2013 at the National Cancer Center were reviewed retrospectively. Results: The patients consisted of 11 males and six females. The mean age was 41 years old (range, 8 74). The mean number of therapeutic leukapheresis per patient was two (range, 1 4). Clinical symptoms improved in 14 patients (82%) after therapeutic leukapheresis and three patients (18%) were not yet to improve. The mean WBC count was significantly reduced by 32.6% (±17.4) after therapeutic leukapheresis, from 250,146/μL (±117,000) to 174,702/μL (±104,700) (P<0.001). The mean volume of single removal was 298 ml with /L (±1.54) WBCs. After therapeutic leukapheresis, the mean platelet count showed a decline from /L (±43) to /L (±26). However, the prothrombin time (PT) and activated partial thromboplastin time (aptt) did not show a significant increase (PT, P=0.637; aptt, P=0.054). Conclusion: Therapeutic leukapheresis is demonstrated as an effective and safe treatment that can improve symptoms and reduce leukocytes in hyperleukocytosis. (Korean J Blood Transfus 2014;25: ) Key words: Therapeutic leukapheresis, Leukostasis, Hyperleukocytosis Received on August 1, Revised on August 12, Accepted on August 13, 2014 Correspondence to: Sun-Young Kong Department of Laboratory Medicine, Center for Diagnostic Oncology, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang , Korea Tel: , Fax: , ksy@ncc.re.kr This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright C 2014 The Korean Society of Blood Transfusion

2 이세나외 : 백혈구증다증환자에서치료적백혈구성분채집술의임상적효과및안전성 서론 급성백혈병에서초기백혈구수나골수아세포수가 100,000/μL 이상으로증가하는백혈구증다증은 1) 병의진행에중요한영향을미치며, 성인급성골수성백혈병의경우 5 13%, 급성림프구성백혈병은 10 30% 에서나타난다. 2,3) 백혈구의급속한증가는백혈구울체, 침윤, 혈전으로이어지고이로인한뇌, 폐, 신장, 간등의비가역적장기손상과출혈의위험으로조기사망률및합병증이증가한다. 4) 백혈구증다증의지지적치료로수분공급과호흡지지등증상에따른치료가있고, 적극적치료로는백혈구세포제거술과 allopurinol 투여가있다. 특히치료적백혈구채집술은화학요법의약제투여전혈액내순환백혈구수를빠르게감소시킬수있는응급시술로진단초기에시행할수있다. 5,6) 효과적백혈구성분채집술을위해서는 2 blood volume 또는 8 10 L 이상의순환혈액의시술이권장되며, 성인환자의경우시술적응여부에따라총순환혈액량의증가도제시하고있다. 성인의권장평균백혈구제거량은 600 ml로교질 (colloid), 결정질 (crystalloid) 또는다른혈액제제의대체용액투여가제안된다. 7) 시술시혈액량에따라 1 blood volume은순환세포의 63%, 2 blood volume은순환세포의 87% 의제거로체내총백혈구수는 20 50% 정도가감소하는것으로보고된다. 3) 백혈구제거술의부작용으로는시술전중심정맥관확보시발생하는출혈등부작용, 백혈구제거와함께불가피하게손실되는혈소판의감소와이로인한출혈경향의증가 5) 항응고제에의한이온칼슘의감소로인한저칼슘혈증등이있고이에대한예방과대처가원활한시술진행과시술효과에영향을미친다고보고되었다. 8) 이에본연구는백혈구증다증으로치료적성분채집술을시행한환자의임상적특성과치료전, 후의혈액학적지표들을비교하여치료적백혈구성분채집술의임상적효과와안전성을알아보고향후환자치료계획에도움을주고자시행하였다. 대상및방법 1. 대상 2005년 5월부터 2013년 10월까지국립암센터에서백혈구증다증을동반하여치료적백혈구성분채집술을시행한환자 17명의임상기록과시행된 39건의치료적백혈구성분채집술시술기록을조사하였다. 진단당시의환자의성별, 나이, 임상증상및질환과시술전후의혈액학적지표와임상양상을후향적으로분석하였다. 2. 방법치료적백혈구성분채집술을시행한백혈구증다증환자의임상기록을통하여성별, 나이, 동반질환을조사하였고, 시술전, 후임상증상과질환의개선유무를관찰하였다. 치료적성분채집술은연속적성분채집기인 CS 3000 Plus (Fenwal Inc., Lake Zurich, IL, USA). COBE Spectra (Terumo, BCT, Lakewood, CO, USA) 를이용하였고, 시술에사용되는항응고제는 ACD-A (anticoagulant citrate dextrose formula A) 이었다. 환자별로시술기록지와병록기록을조회하여시술횟수, 진행된총혈액량과채집된혈액량등과시술전, 후의혈액학적지표의변화를분석하였다. 치료경과는시술전, 후혈액지표와임상증상을조사하였고, 시술후임상증상의개선은마지막시술을마친 1일후의임상의가기록한의무기록지를분

3 Korean J Blood Transfus Vol. 25, No. 2, , Aug 석하였다. 혈액학적지표중백혈구, 적혈구, 헤마토크릿, 혈색소, 혈소판은 XE-2100 (Sysmex, Kobe, Japan) 으로측정하였고, 프로트롬빈시간, 활성화트롬보플라스틴수치는 2005년부터 2007 년 10월까지는 Coagrex-800 (Sysmex, Kobe, Japan) 로, 2007년 11월부터는 STAGO-R1 (DIAGNOSTICA STAGO, Asnières, France) 로측정하였다. 통계분석은 STATA 9.2/SE 9.2 for windows (StataCorp LP, College station TX 77845, USA) 로분석하였고, 치료적백혈구성분채집술전, 후의헤마토크릿및혈색소, 혈소판, 프로트롬빈시간, 활성화트롬보플라스틴수치변화를비교하기위해 Wilcoxon signed rank test로검정하였고, P value가 0.05 미만인경우통계적유의하다고판정하였다. 결과 1. 대상환자특성백혈구증다증으로치료적백혈구성분채집술을시행한환자17명의중앙연령은 41세 (8 74 세 ) 이었고, 성별분포는남자가11명 (65%), 여자가 6명 (35%) 이었다. 시술환자는성인 11명 (65%), 소아 6명 (35%) 으로질병빈도순위로나열하면전구체B-세포림프모구성백혈병 5명 (30%), 미성숙급성골수성백혈병 3명 (17%), 전구체 T-세포림프모구성백혈병 2명 (11%) 순이었고, 성숙급성골수성백혈병, 상세불명급성림프성백혈병, 급성골수단핵구성백혈병, 분생형만성골수성백혈병, 상세불명만성림프성백혈병, B-세포형전림프구성백혈병, 급성골수모세포성백혈병이각 1명 (6%) 이었다 (Table 1). 시술전주증상은발열이 9예로가장많았고, 전신쇠약감이 7예, 두통, 오심, 상복부불편감, 폐 렴, 자반증이각 3예, 시력저하, 심부정맥혈전증, 흉통이각 2예였으며, 어지러움증, 구토, 피로감, 폐색전증, 파종성혈액응고장애, 산소포화도감소가각 1예에서나타났다 (Table 2). 2. 치료적백혈구성분채집술대상환자 17명에서치료적백혈구성분채집술은총 39건시행되었고, 시술에사용된성분채집기는 CS 3000 Plus가 13건 (33%), COBE Spectra가 26건 (67%) 이었다. 환자전체의평균시술횟수는 2회 (1 4회) 로 1회시술만을시행한환자는 4명 (23.6%), 2회가 6명 (35.4%), 3회가 5명 (29.5%), 4회가 2명 (11.8%) 이었으며, 시술도중부작용으로시술을중단한경우는없었다. 환자의평균총혈액량은 3829 (±837) ml이었고, 시술중순환된총혈액량은 8808 (±2044) ml이었다. 1회채집된백혈구용적은 298 ml였으며, 채집된총백혈구수는평균 /L (±1.54) 로평균 32.6% (±17.4) 의제거율을나타냈다. 시술전평균백혈구수는 250,146/μL (±117,000) 에서시술후 174,702/μL (±104,700) 로통계학적으로유의한감소 (P<0.001) 를보였다. 시술전평균혈색소는 8.86 (±1.7) g/dl에서 8.62 (±1.8) g/dl이었으며, 출혈과관련된요인으로시술전혈소판수는 84,589/μL (±42.83) 에서시술후 71,025/μL (±25.62) 로유의한감소 (P=0.002) 를보였으나프로트롬빈시간 (P=0.637), 활성화트롬보플라스틴수치 (P=0.054) 는통계적으로유의한증가를보이지않았다 (Table 3). 채집된평균백혈구의제거율은시술 1회차시, 33.1% (±20.2), 시술 2회차시, 31.7% (±15.3), 시술 3회차시, 34.3% (±10.3), 시술 4회차시, 27.4% (±38.1) 이었다 (Table 4). 3. 치료적백혈구성분채집술후임상경과시술후임상증상의개선을보인환자는 14명

4 이세나외 : 백혈구증다증환자에서치료적백혈구성분채집술의임상적효과및안전성 Table 1. Summary of clinical characteristics and parameters of the patients treated by therapeutic leukapheresis No. of patient Age/Sex Diagnosis No. of procedure WBC count (/μl) WBC reduction Initial* Final efficacy (%) Symptom improvement 1 8/F Precursor B cell lymphoblastic leukaemia 2 98,820 36, Yes 2 11/M Acute myeloid leukaemia with maturation 1 129,000 60, Yes 3 11/F Acute lymphoid leukaemia, unspecified 1 244,070 98, Yes 4 12/M Precursor T cell lymphoblastic leukaemia 1 204,130 73, Yes 5 15/M Precursor B cell lymphoblastic leukaemia 3 470, , Yes 6 15/M Precursor T cell lymphoblastic leukaemia 3 274,740 57, Yes 7 35/M Acute myelomonocytic leukaemia 2 411,860 54, Yes 8 42/F Acute myeloid leukaemia without maturation 3 178,010 95, Yes 9 45/F Precursor B cell lymphoblastic leukaemia 4 431, , Yes 10 45/F Chronic myeloid leukaemia in blastic phase 2 352, , Yes 11 60/M Acute myeloid leukaemia without maturation 3 265, , Yes 12 64/M Chronic lymphocytic leukaemia, unspecified 2 561, , Yes 13 69/F Prolymphocytic leukaemia of B cell type 3 217, , Yes 14 72/M Precursor B cell lymphoblastic leukaemia 4 248, , Yes 15 58/M Precursor B cell lymphoblastic leukaemia 1 133, , No 16 69/M Acute myeloid leukaemia without maturation 2 333,040 70, No 17 74/M Acute monoblastic leukaemia 2 192, , No Mean 279, , SD 130,199 70, * Intial represents WBC count prior to the first leukapheresis and final represents WBC count after the last leukapheresis

5 Korean J Blood Transfus Vol. 25, No. 2, , Aug (82%), 증상의개선을보이지않은환자는 3 명 (18%) 이었다. 소아환자의경우 6명모두증상개선효과가있었으나성인환자 11명중 3명은증 Table 2. Pre-treatment symptoms of the patients treated by therapeutic leukapheresis Symptoms No. of patients (%) Fever 9 (21%) General weakness 7 (17%) Headache 3 (7%) Nausea 3 (7%) Epigastric discomfort 3 (7%) Pneumonia 3 (7%) Petechiae 3 (7%) Visual disturbance 2 (4.2%) Deep vein thrombosis 2 (4.2%) Chest pain 2 (4.2%) Dizziness 1 (2.4%) Vomiting 1 (2.4%) Fatigue 1 (2.4%) Pulmonary embolism 1 (2.4%) Disseminated intravascular coagulation 1 (2.4%) Hypoxia 1 (2.4%) 상개선이없었다. 소아평균백혈구제거율은 64.7% 이었고, 성인환자는 44.9% 로나타났다. 소아환자의경우성인환자보다임상증상과백혈구제거율에서높은효과를보였다. 증상개선이없는성인환자 3예를조사한결과는다음과같다. 환자1예는 69세남자로, 미성숙급성골수성백혈병으로진단되어 2회의시술을시행하였고, 백혈구제거율은 78.9% 로높았으나시술전발열, 전신쇠약감, 폐렴의 3가지임상증상모두개선효과를보이지않았으며시술직후자의퇴원을 Table 4. The reduction efficacy of therapeutic leukapheresis according to each cycle Cycle Average WBCs reduction (Mean±SD) (%) 1 st 33.1± nd 31.7± rd 34.3± th 27.4±38.1 Total 32.6±17.4 Table 3. Summary of procedure parameters of therapeutic leukapheresis Parameter Pre-procedure (mean±sd) Post-procedure P value* No. of therapeutic leukapheresis procedures (n=39) Total blood volume (ml) 3829±837 Total processing volume (ml) 8808±2044 Volume of removed WBC (ml) 298±71 Removed WBC count ( /L) 4.25±1.54 WBC count (/μl) 250,146±117,0 174,702±104,7 <0.001 Hb (g/dl) 8.86± ± PLT (μl) 84,589±42,83 71,025±25, PT (INR) 1.36± ± aptt (sec) 36.5± ± Abbreviations: SD, Standard deviation; P, P value; WBC, White blood cell; Hb, Hemoglobin; PLT, Platelet; PT, prothrombin time; aptt, activated partial thromboplastin time. *Wilcoxon signed rank test for parameters pre and post procedure was performed

6 이세나외 : 백혈구증다증환자에서치료적백혈구성분채집술의임상적효과및안전성 하여경과관찰이불가능하였다. 환자 2예는 58 세남자로, 심부혈전증의임상증상을동반한전구체 B-세포림프모구성백혈병으로진단되어 1회시술을시행하였으나백혈구제거율은 6.4% 로낮은제거율을보였다. 심부혈전증의임상증상도개선효과가없었으며타병원전출로경과개선에대한정보를얻을수없었다. 환자 3예는 74세남자로, 급성골수모세포성백혈병으로진단되어 2회의시술후, 백혈구제거율은 41.2% 이었으나시술전임상증상인, 발열, 폐렴은개선효과를보이지않았으며시술종료 2일후심정지로사망하였다. 시술후임상증상개선효과가있는환자의 14명경우, 모두시술후화학요법치료를시작하였다 (Table 1). 고찰치료적백혈구성분채집술은백혈구울체를동반한백혈구증다증환자의임상적치료로 American Society for Apheresis (ASFA) 의가이드라인에서는 category I로분류되었으며, 9) 시술목표는순환혈액내의백혈구수를감소시켜백혈구울체현상을줄이고종양용해증후군과파종성혈관내응고증후군을최대한막는것이다. 본연구는치료적백혈구성분채집술의효과와안전성을평가하고자총 17명환자의임상기록지와 39건의치료적백혈구성분채집술의시술기록지를조사하여시술전환자의임상적특성과시술전후의혈액검사결과등을분석하였다. 치료적백혈구성분채집술의시술량은 2 blood volume 또는 8 10 L를권장하고있으며환자의시술적응에따라시술량을증가하는것을권장하고있다. 시술중나타날수있는부작용의관찰을위하여활력증후를측정하고 1회시술로 20 50% 의백혈구수감소를유도한다. 3) 본연구에 서환자의평균시술량은 8808 (±2044) ml이었고, 1회시술로제거된백혈구수는평균 32.6% (±17.4) 로이전연구에서 1회차의시술후백혈구제거율이각각 20% 10), 30.3% 8), 55% 11) 로나타난것과유사한결과를보였다. 8,10-12) 2013년 Kurnaz 등의연구 12) 에서는치료적백혈구성분채집술중대체혈액의투여유무에따라혈소판, 혈색소, 프로트롬빈시간, 활성화트롬보플라스틴수치를나누어비교한결과는혈소판, 혈색소는통계적으로유의한감소가없었고, 프로트롬빈시간, 활성화트롬보플라스틴수치도통계적으로유의한증가가없었다. 1998년국내 Lee 등 8) 의연구에서도혈소판, 혈색소수치는통계적으로유의한감소가없었다. 본연구에서는시술전, 후프로트롬빈시간, 활성화트롬보플라스틴수치는통계적으로유의한증가는없었으나혈소판수는통계적으로유의하게감소하였다. 본연구에서는시술중대체혈액이투여되지않았으며, 혈액검사시간은시술종료 1시간직후시행하였다. 그러나타연구에서는시술중대체혈액이투여되었으며, 12) 시술후혈액검사시간에대한명확한언급이없어 8,12) 본연구결과와비교하기는어려울것으로사료된다. 이에본연구자들은혈소판의감소가시술로인한감소, 또는질환에서기인된범혈구감소증의원인으로추측해보며, 시술부작용을예방하기위하여시술전, 후혈색소, 혈소판수치의교정과추후연구가반드시필요할것으로본다. 백혈구증다증은성인급성골수성백혈병의경우 5 13%, 급성림프성백혈병은 10 30% 에서보고하고있으며, 백혈구울체는급, 만성림프성백혈병보다급성골수성백혈병에서더많이나타난다고보고하고있다. 13) 백혈구증다증은이차적으로백혈구울체 (leukostasis), 종양용해증후군 (tumor lysis syndrome), 파종성혈관내응고증후군 (dissem

7 Korean J Blood Transfus Vol. 25, No. 2, , Aug inated intravascular coagulopathy) 등이한가지이상발생하여병의높은이환율과사망률로이어진다. 종양용해증후군은빠른세포파괴의결과로고요산증, 고칼륨혈증및저칼슘혈증과같은대사이상으로비가역적장기반응이나타나고, 발열, 신장장애, 심장부정맥, 심정지, 사망등의결과를초래한다. 파종성혈관내응고증후군은응고단백, 혈소판의작은혈전의형성으로정상적인혈액응고장애및심한출혈경향의증가가나타난다. 14) 백혈구울체는백혈구증다증의뚜렷한임상양상으로과다백혈구수증가는혈관폐색으로조직의저산소증이유도되며의식혼란, 현기증, 두통, 이명, 시력저하, 운동장애등의신경계 (neurology system) 이상과호흡곤란, 빈호흡, 저산소혈증등의호흡기계 (respectory system) 이상이발생된다. 9,15) 2005년 Novotny 등 16) 은백혈구증다증백혈병환자에서백혈구울체의증상을신경학적, 호흡기계및그밖의증상에따라점수를측정하여 none, possible, probable, highly probable의 4가지로등급을분류하였다. 본연구에서는 grade 1은 10 명, grade 2는 2명, grade 3은 4명으로나타났으며, 시술후, 임상증상호전이없는 3예는 grade 3의높은점수로나타났다. 혈액학적지표와점수분류에따른연관성은연구대상수의부족으로통계적유의성을나타낼수없으나추후추가적인연구가필요할것으로사료된다. 2007년 Bug 등과 2008년 Marbello 등의급성골수성백혈병환자를대상으로하는연구에서는 LDH, 혈청크레아티닌>1.2 mg/dl, PT<60%, CRP, 호흡곤란등이진단 3주내조기사망과관련있는위험요인으로보고하였다. 17,18) 그러나 2009년 Piccirillo 등 19) 의연구에의하면 highly probable 그룹은휠씬더큰조기사망의위험이 있으며, 단변량분석에의한결과로 70세이상의연령, 혈청 LDH>2000 UI/L, 혈청빌리루빈>1.5 mg/dl, 혈청크레아티닌>1.2 mg/dl은조기사망률에통계학적으로유의하지않음을보고하였다. 본연구대상자는시술전, 후의 LDH, 혈청크레아티닌, 혈청빌리루빈, CRP등의혈액학적지표의정보누락과타병원전원, 자의퇴원등으로시술후임상증상의개선과조기사망여부를확인할수있는정보가부족하여통계학적인유의성을알수없었다. 따라서추후이를보완한연구가요구된다. 본연구의치료적백혈구성분채집술총 39건에서시술부작용은없었으며, 백혈구증다증을동반한백혈병환자에서치료적백혈구성분채집술은항응고제에의한출혈위험에도불구하고, 급, 만성으로발생한과다백혈구를제거하는안전하고효과적인시술임이확인되었으며향후추가적인연구가더필요하다고본다. 요약배경 : 치료적백혈구성분채집술은백혈구증다증을동반한백혈병환자에서화학요법치료에앞서순환백혈구수의감소를목적으로하는효과적인응급시술이다. 그러나시술중사용하는항응고제에의한출혈경향이부작용으로존재한다. 본연구는백혈구증다증을동반한백혈병환자의임상적특성과치료적백혈구성분채집술치료전후의혈액학적지표들을비교하여치료적백혈구성분채집술의효과및출혈경향에미치는영향을평가해보고, 환자의향후치료계획에도움을주고자시행하였다. 방법 : 2005년 5월부터 2013년 10월까지국립암센터에서백혈구증다증을동반하여치료적백혈구성분채집술을시행한 17명의환자의임상기록

8 이세나외 : 백혈구증다증환자에서치료적백혈구성분채집술의임상적효과및안전성 과 39건의치료적백혈구성분채집술시술기록을조사하여시술전후의혈액학적지표와임상양상을후향적으로분석하였다. 결과 : 대상환자의연령은 41세 (8 74세) 로남자 11명, 여자 6명이었다. 시술직후임상증상은 14명 (82%) 에서개선되었고, 3명 (18%) 에서는증상개선효과가없었다. 시술평균횟수는 2회 (1 4회 ) 로 1회시술만을시행한환자는 4명 (23.6%), 2회가 6명 (35.4%), 3회가 5명 (29.5%), 4회가 2명 (11.8%) 이었다. 시술전평균백혈구수는 250,146/μL (±117,000) 에서시술후 174,702/μL (±104,700) 로통계적으로유의한감소 (P<0.001) 를보였다. 제거된백혈구용적은 298 ml 였으며, 제거된총백혈구수는평균 /L (±1.54) 로평균 32.6% (±17.4) 의제거율을나타냈다. 시술전혈소판수는 /L (±43) 에서시술후 /L (±26) 로감소되었으나프로트롬빈시간 (P=0.637), 활성화트롬보플라스틴수치 (P=0.054) 는통계적으로유의한증가를보이지않았다. 결론 : 백혈구증다증에서치료적백혈구성분채집술은과다백혈구를제거하는안전하고효과적인시술임이확인되었다. References 1. Porcu P, Danielson CF, Orazi A, Heerema NA, Gabig TG, McCarthy LJ. Therapeutic leukapheresis in hyperleucocytic leukaemias: lack of correlation between degree of cytoreduction and early mortality rate. Br J Haematol 1997; 98: Porcu P, Cripe LD, Ng EW, Bhatia S, Danielson CM, Orazi A, et al. Hyperleukocytic leukemias and leukostasis: a review of pathophysiology, clinical presentation and management. Leuk Lymphoma 2000;39: Ganzel C, Becker J, Mintz PD, Lazarus HM, Rowe JM. Hyperleukocytosis, leukostasis and leukapheresis: practice management. Blood Rev 2012;26: Piro E, Carillio G, Levato L, Kropp M, Molica S. Reversal of leukostasis-related pulmonary distress syndrome after leukapheresis and low-dose chemotherapy in acute myeloid leukemia. J Clin Oncol 2011;29:e Tan D, Hwang W, Goh YT. Therapeutic leukapheresis in hyperleukocytic leukaemias-- the experience of a tertiary institution in Singapore. Ann Acad Med Singapore 2005;34: Hölig K, Moog R. Leukocyte depletion by therapeutic leukocytapheresis in patients with leukemia. Transfus Med Hemother 2012;39: Shelat SG. Practical considerations for planning a therapeutic apheresis procedure. Am J Med 2010;123: Lee YW, Jeong GY, Koo HH, Lee HG, Kim DW. Evaluation of therapeutic leukapheresis in hyperleukocytic leukemias. Korean J Blood Transfus 1998;9: Schwartz J, Winters JL, Padmanabhan A, Balogun RA, Delaney M, Linenberger ML, et al. Guidelines on the use of therapeutic apheresis in clinical practice-evidence-based approach from the Writing Committee of the American Society for Apheresis: the sixth special issue. J Clin Apher 2013;28: Lee YK, Han KS. Clinical experiences of therapeutic leukapheresis. Korean J Blood Transfus 1996;7: Chang MC, Chen TY, Tang JL, Lan YJ, Chao TY, Chiu CF, et al. Leukapheresis and cranial irradiation in patients with hyperleukocytic acute myeloid leukemia: no impact on early mortality and intracranial hemorrhage. Am J Hematol 2007;82:

9 Korean J Blood Transfus Vol. 25, No. 2, , Aug Kurnaz F, Sivgin S, Pala C, Yildirim R, Baldane S, Kaynar L, et al. The effect of volume replacement during therapeutic leukapheresis on white blood cell reduction in patients with extreme leukocytosis. Transfusion 2013;53: Stucki A, Rivier AS, Gikic M, Monai N, Schapira M, Spertini O. Endothelial cell activation by myeloblasts: molecular mechanisms of leukostasis and leukemic cell dissemination. Blood 2001;97: Dixit A, Chatterjee T, Mishra P, Kannan M, Choudhry DR, Mahapatra M, et al. Disseminated intravascular coagulation in acute leukemia at presentation and during induction therapy. Clin Appl Thromb Hemost 2007;13: De Santis GC, de Oliveira LC, Romano LG, Almeida Prado Bde P Jr, Simoes BP, Rego EM, et al. Therapeutic leukapheresis in patients with leukostasis secondary to acute myelogenous leukemia. J Clin Apher 2011;26: Novotny JR, Müller-Beissenhirtz H, Herget- Rosenthal S, Kribben A, Dührsen U. Grading of symptoms in hyperleukocytic leukaemia: a clinical model for the role of different blast types and promyelocytes in the development of leukostasis syndrome. Eur J Haematol 2005;74: Bug G, Anargyrou K, Tonn T, Bialleck H, Seifried E, Hoelzer D, et al. Impact of leukapheresis on early death rate in adult acute myeloid leukemia presenting with hyperleukocytosis. Transfusion 2007;47: Marbello L, Ricci F, Nosari AM, Turrini M, Nador G, Nichelatti M, et al. Outcome of hyperleukocytic adult acute myeloid leukaemia: a single-center retrospective study and review of literature. Leuk Res 2008;32: Piccirillo N, Laurenti L, Chiusolo P, Sorà F, Bianchi M, De Matteis S, et al. Reliability of leukostasis grading score to identify patients with high-risk hyperleukocytosis. Am J Hematol 2009;84:

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012임수진 Received : 2012. 11. 27 Reviewed : 2012. 12. 10 Accepted : 2012. 12. 12 A Clinical Study on Effect of Electro-acupuncture Treatment for Low Back Pain and Radicular Pain in Patients Diagnosed with Lumbar