대한수혈학회지 : 제 27 권제 3 호, 2016 The Korean Journal of Blood Transfusion Vol. 27, No. 3, 247-256, December 2016 https://doi.org/10.17945/kjbt.2016.27.3.247 pissn 1226-9336 eissn 2383-6881 Original Article 호중구감소증환자의감염에서과립구수혈치료분석 : 단일기관경험 이세나 1, * ㆍ허유미 1, * ㆍ엄현석 2,3 ㆍ이혜원 2 ㆍ이은영 2 ㆍ공선영 1,3,4 국립암센터부속병원진단검사센터진단검사의학과 1, 혈액암센터 2, 국제암대학원대학교시스템종양생물학과 3, 국립암센터연구소임상역학연구과 4 Analysis of Granulocyte Transfusions in Patients with Infections and Neutropenia: A Single Center Experience Se-Na Lee 1, *, Youmi Hu 1, *, Hyeon Seok Eom 2,3, Hyewon Lee 2, Eunyoung Lee 2, Sun-Young Kong 1,3,4 Department of Laboratory Medicine, Center for Diagnostic Oncology 1, Center for Hematologic Malignancy 2, Department of System Cancer Science, Graduate School of Cancer Science and Policy 3, Translational Epidemiology Branch, Hospital and Research Institute 4, National Cancer Center, Goyang, Korea Background: Granulocyte therapy has been used as supportive care for patients with prolonged neutropenia after intensive chemotherapy or peripheral blood stem cell transplantation (PBSCT). Here, we investigated clinical factors of granulocyte therapy for neutropenic patients with infection to evaluate its efficacy and safety. Methods: A retrospective analysis of 25 neutropenic patients treated with 99 granulocyte collection and granulocyte therapy from October 2011 to April 2016 at the National Cancer Center was conducted. Two groups, a count recovery group with a cut off of >1,000/ L and a no recovery group were compared and symptoms related with granulocyte were analyzed. Results: Granulocyte collection and s were performed in 99 procedures. After granulocyte therapy, 21 patients (84%) showed count recovery, whereas 4 patients (16%) had no response. Significant differences in pre-absolute neutrophil count (29/ L vs. 0/ L, P=0.048), duration of neutropenia before granulocyte (11 days vs. 26 days, P=0.011), and total number of granulocyte (2 times vs. 11 times, P=0.049) were observed between groups. Temporary symptoms related granulocyte were observed in seven patients (28%); however, all patients showed clinical improvement. The median of the single volume was 220 ml (200 to 397 ml) and the mean total granulocyte content was 4.92 10 10. Conclusion: Granulocyte therapy is safe and effective for patient with life threatening neutropenia and infection, also considerable for early onset trial for granulocyte. (Korean J Blood Transfus 2016;27:247-256) Key words: Leukocyte, Neutropenia, Infection Received on December 2, 2016. Revised on December 9, 2016. Accepted on December 9, 2016 Correspondence to: Sun-Young Kong Department of Laboratory Medicine, Center for Diagnostic Oncology and Translational Epidemiology Research Branch, Hospital and Research Institute, Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 10408, Korea Tel: 82-31-920-1735, Fax: 82-31-920-1268, E-mail: ksy@ncc.re.kr *Se-Na Lee and Youmi Hu contributed equally as co-first authors. This work was supported by National Research Foundation of Korea (NRF) funded by the Korean government (MSIP) under Grant 2014R1A2A2A01002553. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright C 2016 The Korean Society of Blood Transfusion - 247 -
Korean J Blood Transfus Vol. 27, No. 3, 247-256, Dec. 2016 서론 대상및방법 골수의과립구생산기능부전또는고용량항암화학요법과조혈모세포이식치료과정중에서발생한호중구감소증은세균과진균감염의주요원인으로감염의치료를위해항생제와조혈촉진인자의투여에도불구하고여전히높은유병율과사망률을보이고있다. 1-3) 정상인으로부터채집된과립구를이용한수혈치료는고위험호중구감소증환자에서감염을치료할수있는접근이가능하고유용한방법으로다양한임상연구를통해충분한수의과립구수혈치료가감염회복및환자의골수에서과립구재생산능력이있음을보고하였다. 4) 최근에는헌혈자에게효과적인과립구가동화를위하여과립구집락인자 (5.0 10.0 g/kg) 와추가로덱사메타손의투여등으로혈중호중구수치를 5 6배정도로증가시키고과립구수 4 10 10 이상을채집하여환자에게투여함으로써과립구수혈치료의효과를얻을수있었다. 5-7) 하지만임상현장에서는환자의과립구수혈치료를계획하기위해서헌혈자모집, 과립구수혈치료의시작시점과치료기간을결정하는데충분한임상적근거가부족한실정이다. 따라서본연구의목적은호중구감소증환자와감염에서효과적으로과립구수혈치료를계획하기위해관련임상적요소를확인하고과립구수혈치료의안전성및발생가능한수혈부작용의예방에도움을주고자단일기관의연구자료를분석하였다. 1. 수혜자와과립구헌혈자 2011년 10월부터 2016년 4월까지국립암센터에서고용량항암치료또는조혈모세포이식으로호중구감소증과감염이발생하여과립구수혈치료를받은호중구감소증환자 25명을대상으로하였으며, 수혜자들은과립구성백혈구가 500 10 9 /L 미만으로세균및진균감염으로항생제에저항을보였다. 수혜자의일반적인특성, 감염관련원인, 호중구감소증의기간, 수혈된과립구수및수혈결과등임상적인특성을조사하였다. 헌혈자는과립구수혈치료를받는수혜자와 ABO혈액형이일치하며국내혈액관리법에의거하여헌혈기준에적합한헌혈자로선정하였다. 8) 과립구가동화를위하여시술 12시간전에과립구집락인자를 600 g 피하주사하였고, 덱사메타손 8 mg을경구투여하였다. 또한과립구집락인자투여로나타날수있는전신통증과두통, 피로, 복부불편감등의증상을최소화하기위하여 acetaminophen 650 mg을경구투여하였다. 9) 헌혈자의반복시술은일주일간격으로동일한가동화방법으로시행하였다. 2. 과립구성분채집술과수혈과립구성분채집술은연속적성분채집기인 CS 3000 Plus (Fenwal Inc., Lake Zurich, IL, USA) 와 COBE Spectra (Terumo, BCT, Lakewood, CO, USA) 를사용하였다. 사용된항응고제는적혈구침강제인 10% Pentaspan Injection (Jeil Pharmaceutical CO., LTD, Korea) 500 m와원내약제과에서희석제조한 46.7% trisodium citrate (Kukjeon Parm. CO., LTD, Korea) 30 ml를혼합하여혈액과 1:13의비율로투여하였다. 시술진행속도는 40 60 ml/min - 248 -
이세나외 : 효과적인과립구수혈 로진행하였으며 1 회시술총순환혈액량은 7,000 ml 이하였다. 채집된과립구는수혈과연관된이식편대숙주반응을예방하기위해채집된과립구에 25 Gy의방사선을조사하였고, 수혈 30 분전발열예방을위해 propacetamol 1,000 mg, 두드러기, 소양감등알러지증상예방을위해 chlorpheniramine maleate 4 mg, Hydrocortisone 500 mg 를정주하였다. 수혈부작용관찰을위하여수혈시작시, 수혈 15분후, 수혈을마친후활력증후와수혈부작용을관찰하여기록하였고, 수혈부작용발생시수혈을멈추고임상적인처치를하였으며증상이개선된후, 수혈을진행하였다. 과립구수혈부작용은수혈시작시점에서부터발열반응, 심각한폐합병증과그와관련된저산소증, 혈압강하, HLA동종면역과관련된합병증등을포함한증상들이 6시간이내에발생한것으로환자에게발생한임상적증상으로발열, 오한, 두드러기, 경미한혈압강하등을 경미한증상, 저산소증, 빈맥, 중증혈압변화, 흉통등알레르기반응과저혈압반응을 중등도증상 및수혈관련급성폐손상, 급성용혈수혈반응을 심각한증상 으로나누어정의하였다. 10) 과립구수혈치료의중단은환자의절대호중구수가 >1,000/ L이상으로증가되거나감염및임상증상의악화로임상의사의판단하에치료를중단하였다. 3. 통계 과립구수혈치료후절대호중구수가 >1,000/ L 이고임상적증상이호전되어과립구수혈치료를중단한환자를 회복군 으로정의하였고절대호중구수가 <1,000/ L이고임상적증상이악화되어의사의판단하에과립구수혈치료를중단한환자를 비회복군 으로정의하였다. 10) 통계분석에사용한프로그램은 STATA 12.0 for windows (StataCorp LP, College station TX 77845, USA) 이 었다. 헌혈자와과립구성분채집술관련변수들및과립구수혈치료를받은수혜자의임상적특성은서술적통계로분석하였고, 과립구수혈치료과정중에나타난수혈부작용및임상적증상개선과정을기술하였다. 또한과립구수혈치료의반응유무에따른변수들의차이는 Wilcoxon- Mann-Whitney U-test로검정하였다. P value가 0.05 미만인경우통계적으로유의하다고판정하였다. 결과 1. 환자의임상적특성과립구수혈치료를받은환자 25명의평균연령은 51세였고, 성별분포는남자가 15명 (60%), 여자가 10명 (40%) 이었다. 환자들의평균체중은 59 kg이었다. 과립구수혈치료를받은환자의진단명은급성골수성백혈병 15명 (48%), 급성림프성백혈병 5명 (20%), 만성골수성백혈병 4명 (16%), 다발골수종 3명 (12%), 악성림프종 1명 (4%) 이었다. 호중구감소증의원인별분류는항암치료로인한환자는 22명 (88%), 동종말초조혈모세포이식술로인한환자는 2명 (8%), 자가말초조혈모세포이식술에의한환자는 1명 (4%) 이었다. 환자들의감염양상은진균감염이 19명 (76%), 박테리아감염이 5명 (20%) 였으며진균과박테리아에모두감염된환자는 1명 (4%) 이었다. 시행한과립구성분채집술의총건수는 99건으로환자한명당시행한과립구수혈치료횟수의중앙값은 2회 (1 8 회 ) 이고수혈치료이전호중구감소증이나타난기간은평균 11일 (1 51일) 이었다 (Table 1). 2. 과립구성분채집과헌혈자의특성 CS 3000 Plus로 62건 (63%), COBE Spectra로 37 건 (37%) 을시행하였다. 과립구성분채집의헌혈 - 249 -
Korean J Blood Transfus Vol. 27, No. 3, 247-256, Dec. 2016 Table 1. Clinical characteristics of patients Characteristics N (%), Mean±SD or median (range) No. of patient 25 Age 51.1±10.8 Gender Male 15 (60%) Female 10 (40%) Body weight (kg) 59.3±8.6 Disease AML 12 (48%) ALL 5 (20%) CML 4 (16%) MM 3 (12%) Lymphoma 1 (4%) Cause of neutropenia Chemotherapy 22 (88%) Allogeneic PBSC 2 (8%) transplantation Autologous PBSC 1 (4%) transplantation Underlying infections Fungal 19 (76%) Bacterial 5 (20%) Fungal+Bacterial 1 (4%) Number of GTXs/patient 2 (1 18) (range) Duration of neutropenia before 11 (1 51) granulocyte (days) Abbreviations: AML, acute myeloid leukemia; ALL, acute lymphoblastic leukemia; CML, chronic myeloid leukemia; MM, multiple myeloma; PBSC, peripheral blood stem cells; GTX, granulocyte. 자들은모두 90명이었고, 평균연령은 29세 (18 52세 ) 이었다. 헌혈자들의성별분포는남자가 86 명 (96%), 여자가 4명 (4%) 이었다. 채집된과립구의용적의중앙값은 220 ml (200 397 ml) 이었다. 순환된총혈액량의중앙값 ( 범위 ) 은 6,700 ml (3,500 7,600 ml) 이었고, 채집된단위혈액당 Table 2. Summary of donors and granulocyte collection Parameter Mean±SD or median (range) No. of donors 90 Age (years) 29 (18 52) Gender (male/female) 86/4 No. of leukapheresis 99 Product volume (ml) 220 (200 397) TPV (ml) 6,700 (3,500 7,600) Total WBC content ( 10 10 ) 6.32±1.71 Total granulocyte content 4.92±1.46 ( 10 10 ) Total granulocyte content 0.80±0.30 ( 10 8 /kg) Abbreviations: TPV, total processing volume; WBC, white blood cells. 과립구의수는 6.32±1.71 ( 10 10 granulocytes) 이었다 (Table 2). 3. 과립구수혈치료효과와임상지표비교 과립구수혈치료후절대호중구수가 >1,000/ L 이상으로회복되는혈액학적반응을보인환자군 ( 회복군 ) 과혈액학적반응을보이지않은환자군 ( 비회복군 ) 두군으로나누어비교분석하였다. 총 25명의환자가과립구수혈치료를받았으며치료받은환자중 21명 (84%) 의환자에게혈액학적반응이있었고, 4명 (16%) 의환자는혈액학적반응을보이지않았다 (Table 3). 두군간에환자나이, 과립구수혈치료전절대호중구수, 호중구감소증의기간, 과립구수혈치료전 G-CSF의사용기간, 과립구수혈치료횟수, 평균수혈된백혈구수치와과립구수치의차이를비교분석하였다. 과립구수혈치료후절대호중구수가 1,000/ L 이상으로회복하여혈액학적반응을보인환자연령의중앙값은 53세 (22 71세) 이었고, 수혈치료전절대호중구수의중앙값은 - 250 -
이세나외 : 효과적인과립구수혈 Table 3. Clinical characteristics of patients and granulocyte No. Age (years) Sex Diagnosis Duration of neutropenia before granulocyte (days) Duration of G-CSF prior granulocyte (days) Type of infection WBC at start of granulocyte ( 10 9 /L) WBC after 1hr of granulocyte ( 10 9 /L) WBC after 1day of granulocyte ( 10 9 /L) Total number of granulocyte (times) Outcome P1 61 Male AML 78 51 Bacterial 0.04 1.37 0.51 14 No recovery P2 65 Male AML 42 30 Fungal 0.06 3.11 2.1 1 No recovery P3 42 Female AML 27 21 Fungal 0.03 1.48 0.4 8 No recovery P4 39 Male AML 2 21 Fungal 0.2 0.86 0.32 18 No recovery P5 63 Male CML 34 34 Fungal 0.09 0.68 0.35 7 Count recovery P6 63 Male CML 25 10 Fungal 0.01 0.18 0.03 1 Count recovery P7 71 Male AML 22 10 Fungal 0.21 3.7 3.89 3 Count recovery P8 55 Female MM 15 17 Fungal 0.09 4.49 2.09 1 Count recovery P9 57 Male ALL 14 1 Fungal, 0.30 5.95 0.65 4 Count recovery Bacterial P10 47 Male MM 13 4 Fungal 0.39 2.19 2.2 1 Count recovery P11 22 Female DLBL 12 12 Fungal 0.05 4.02 4.21 1 Count recovery P12 60 Female CML 11 10 Bacterial 0.1 0.45 0.49 1 Count recovery P13 35 Female AML 9 21 Fungal 0.22 2.38 1.8 12 Count recovery P14 55 Male ALL 9 14 Fungal 0.08 0.87 0.33 6 Count recovery P15 44 Female AML 9 11 Bacterial 0.08 5.46 4.48 2 Count recovery P16 54 Male ALL 9 9 Fungal 0.12 1.49 1.48 6 Count recovery P17 53 Male MM 8 7 Fungal 0.28 0.74 0.98 1 Count recovery P18 57 Male AML 7 11 Fungal 0.31 1.65 0.85 1 Count recovery P19 53 Female AML 7 11 Fungal 0.09 5.96 3.9 1 Count recovery P20 53 Male CML 6 4 Fungal 0.48 9.13 4.7 1 Count recovery P21 47 Female AML 4 21 Bacterial 0.08 2.37 1.18 5 Count recovery P22 54 Female AML 4 8 Fungal 0.13 0.3 0.19 2 Count recovery P23 44 Female ALL 4 7 Bacterial 0.04 2.44 1.93 1 Count recovery P24 42 Male ALL 3 4 Fungal 0.05 2.0 1.86 2 Count recovery P25 42 Male AML 0 20 Fungal 0.05 1.04 0.54 3 Count recovery Abbreviations: See Table 1 for AML, ALL, CML, MM and DLBL, diffuse large B-cell lymphoma; hr, hour. - 251 -
Korean J Blood Transfus Vol. 27, No. 3, 247-256, Dec. 2016 29/ L (0 374/ L) 이었다. 호중구감소증의기간의중앙값은 11일 (1 50일) 이고과립구수혈전 G-CSF를투여한기간은 9일 (0 34일) 이었다. 과립구수혈치료를시행한횟수는 2회 (1 12회) 이었고수혈된백혈구수의중앙값은 6.30 10 10 이었다. 수혈된과립구수의중앙값은 4.86 10 10 이었다. 과립구수혈치료후의절대호중구수의회복효과의유무에따라환자나이, 과립구수혈치료전절대호중구수, 호중구감소증의기간, 과립구수혈치료전 G-CSF의사용기간, 과립구수혈치료횟수, 수혈된백혈구수치와과립구수치의차이를조사하였다. 과립구수혈치료전절대호중구수는회복군의중앙값은 29일이고비회복군의중앙값은 0으로유의하였다 (P=0.048). 호중구감소증의기간은회복군의중앙값은 11일, 비회복군의중앙값은 26일로유의하였다 (P=0.011). 과립구수혈치료횟수는회복군의중앙값이 2회, 비회복군의중앙값은 11회로유의한차이가있었다 (P=0.049). 환자의나이 (P=0.941), 수혈된평균백혈구수 (P=0.715), 수혈된평균과립구수 (P=0.340) 는유의한차이를보이지않았다. 또한과립구수혈치료시작전 G-CSF를투여한기간은회복군은 9일 (0 34일), 비회복군은 34일 (0 78) 로차이를 보였으나통계적으로유의한차이는없었다 (Table 4). 4. 과립구수혈부작용과립구수혈치료중부작용을경험한환자는 25명중 7명 (28%) 의환자에게서나타났고, 과립구수혈 99건중 7건 (7%) 에서수혈부작용이나타났다. 대부분의환자는수혈시작후 60분이내에수혈부작용이나타났고 2명의환자가각각 70분, 80분후에수혈부작용이나타났다. 부작용을경험한환자 7명중혈압강하, 발열, 오심, 오한등과같은비용혈성수혈부작용을보인환자는 4명 (16%) 이었으며호흡곤란, 가슴답답함, 빈맥등과같은호흡기증상의부작용을경험한환자는 3명 (12%) 이었다. 중등도증상인용혈성수혈부작용또는수혈관련급성폐손상을보인환자는없었으며수혈부작용으로사망한환자는없었다. 수혈부작용을경험한 7명의환자는체위변경, chlorphenirmine, propacetamol, lorazepam을투여하거나시간을두고관찰함으로증상이호전되었고발생한부작용으로수혈을중단한사례는없었다 (Table 5). Table 4. Variables associated with response to granulocyte Variable Response (N=21) Median (range) No Response (N=4) P value Age of patients 53 (22 71) 51.5 (39 65) 0.941 Pre-ANC of patients (/ L, range) 29 (0 374) 0 (0 6) 0.048 Duration of neutropenia before granulocyte (days) 11 (1 50) 26 (21 51) 0.011 Duration of G-CSF prior granulocyte (day) 9 (0 34) 34.5 (0 78) 0.127 Total number of granulocyte s 2 (1 12) 11 (1 18) 0.049 Infused total WBC content/each ( 10 10 ) 6.30 (1.55 9.40) 6.29 (2.29 9.82) 0.715 Total granulocyte content/each ( 10 10 ) 4.86 (0.73 7.86) 4.71 (1.46 7.34) 0.340 Abbreviations: ANC, absolute neutrophil count; WBC, white blood cells. - 252 -
이세나외 : 효과적인과립구수혈 Table 5. Symptoms related to granulocyte Treatment Outcome Onset time (after ) Sex Diagnosis Symptoms Remarkable vital sign Age (years) No. PR:70 RR:40, SPO2:95 45 min Observation Resolved P9 57 Male ALL Tachypnea/ chest discomfort P10 47 Male MM Mild fever BT:37.6 50 min Propacetamol 2 g IVS Resolved P15 44 Female AML BP down SBP:77, DBP:52 30 min 300 ml Normal Saline Resolved full dropping P17 53 Male MM BP down SBP:88, DBP:52 70 min Semi Fowler's position Resolved P19 53 Female AML Nausea/tachycardia PR:128, RR:20, BT:37.0 20 min Lorazepam 1 mg IVS Resolved P22 54 Female AML Chill/shivering BT:37.8 80 min Chlorpheniramine 4 mg Resolved IVS P25 42 Male AML Mild chest discomfort PR:62, RR:22, SPO2:96 At the start Observation Resolved Abbreviations: AML, acute myeloid leukemia; MM, multiple myeloma; ALL, acute lymphoblastic leukemia; SBP, systolic blood pressure (mmhg); DBP, diastolic blood pressure (mmhg); PR, pulse rate (per min); RR, respiratory rate (per min); BT, body temperature ( o C); SPO2, saturation by pulse oximetry (%); IVS, intravenous side. 고찰 일반적으로과립구수혈치료는항생제와항진 균제에도개선되지않는침습적인진균및박테리아감염과같은급성감염에서시행되었다. 3) 최근의몇몇연구에서는고용량항암화학요법과조혈모세포이식으로인한호중구감소증환자의감염을예방하거나항생제와병행치료를하는방법으로과립구수혈치료를시도하고있다. 4,5) 호중구감소증환자에서감염의치료를위한과립구수혈치료는과립구헌혈자와수혜자에대한면밀한처치를요구한다. 과립구헌혈자의경우는충분한수의과립구를획득하기위해서모집단계, 선발단계및백혈구성분채집술의단계를거친다. 11-13) 헌혈자는과립구집락촉진인자를단독또는스테로이드의동시투여함으로말초혈내의백혈구 / 과립구수를증가시키게되며이과정에서헌혈자의안정성에대한문제와또한백혈구성분채집술로획득된과립구의시간경과에따른세포의생존율에대한의견도제기되어왔다. 또한수혜자인호중구감소증환자는수혈중발생될수있는수혈관련급성폐손상의문제및수혜자의생존율에대한명확한제시의부족등이제기되었으나무작위적임상시험의적용의어려움으로인해명확하게정의되지못하였다. 14-16) 본연구는후향적방법으로호중구감소증과감염의환자에서과립구수혈치료의임상적자료와수혈치료결과를분석하였다. 과립구헌혈자는 90명이었고과립구성분채집술은총 99건이었다. 헌혈자중과립구성분채집술을 1회만시행한환자는 81명이고이들중 9명의헌혈자가 2회를실시하였다. 본연구에서는과립구성분채집술중발생한부작용으로시술을중단한사례는없었으며타연구에서도안전하게시술을진행하였다고보고하였다. 6,9,17,18) 호중구감소증과감염으로과 - 253 -
Korean J Blood Transfus Vol. 27, No. 3, 247-256, Dec. 2016 립구수혈치료를받은환자는 25 명이었고, 이들을 원인별로분류를해보면, 항암요법이 22 명 (80%), 동종조혈모세포이식이 2명 (8%), 자가말초조혈모세포이식이 1명 (4%) 으로항암요법으로인한호중구감소증환자가다수를차지하였다. 이는 2015 년 Price 등 10) 의연구에서항암요법이 36명 (73%), 조혈모세포이식이 8명 (16%), 그밖의다른원인이 5명 (10%) 으로보고된것과비슷한결과를보인다. 여러연구들에서과립구수혈치료후절대호중구수와임상증상의회복율이각각 68.2%, 18) 60%, 19) 50%, 6) 40% 20) 로다양한결과를보였고이들의수혈된평균과립구수는 4 8 10 10 이었다. 본 연구에서는수혈된과립구수는 4.92±1.46 10 10 이었고, 수혈을받은환자의 84% 에서절대호중구수가 1,000/ L 이상으로회복되어본연구가다소높은회복율을보였다. 본연구에서는과립구수혈치료후절대호중구수치회복의반응유무에따라과립구수혈치료전호중구감소증의기간 (P=0.011), 수혈치료전절대호중구수치 (P=0.048), 과립구수혈치료를받은횟수 (P=0.050) 에서두군간에유의한차이를보였다. 국내의 Lee 등 21) 의연구에서수혈치료전호중구감소증의기간 (P=0.207), 수혈치료전절대호중구수 (P=0.273), 과립구수혈치료횟수 (P=0.482) 로유의하지않은분석결과를보였는데, 본연구와과립구수혈치료를시작하는시점의차이로인한요인이다른것이차이가관찰된원인으로생각되었다. 따라서, 향후과립구현혈의효과판정을위한연구에서여러임상적요인중과립구헌혈자의조기확보가능성및명확한과립구수혈치료의시작시점을고려한연구가필요하다고사료된다. 국외의 Rutella 등 22) 의연구에서는과립구수혈치료를통하여감염치료반응에따른예측인자를단변량분석으로보았을때, 과 립구수혈치료이전의질병의상태유무 (P=0.035), 절대호중구수의 500/ L 이상의회복유무 (P< 0.001), 감염범위와정도 (P=0.013) 가통계적으로유의하였다. 과립구수혈부작용이나타난환자는모두 7명 (28%) 이었고경미한수혈작용을보인환자는 4명 (16%) 이었으며발열, 오심, 오한, 혈압강하등의증상으로나타났다. 중등도의수혈부작용을보인환자는 3명 (12%) 이었으며, 호흡곤란, 가습담담함, 빈맥등과같은호흡기와관련된증상으로나타났다. 그외에심각한부작용을보인환자는없었으며이는 2015년 Price 등 10) 의연구에서가벼운과립구수혈부작용을경험한환자가전체의 28%, 중등도의과립구수혈부작용을보인환자가 <5%, 심각한부작용인저산소증을경험한환자가 <1% 가나타난것과비교해보았을때, 본연구에서더낮은과립구수혈부작용발생율을나타냈다. 결론적으로본연구는단일기관의임상결과를분석한것으로과립구수혈치료는호중구감소증환자의감염치료에안전적이고효과적이며치료효과를높이기위해조기의과립구수혈치료가권장된다고할수있다. 요약배경 : 고용량항암요법또는조혈모세포이식후에나타나는호중구감소증환자의중증감염치료를위해과립구수혈치료를하고있다. 본연구는과립구수혈치료를받은감염을동반한호중구감소증환자의임상적특성과지표를조사하여과립구수혈치료후의효과와안전성을평가하고자한다. 방법 : 2011년 10월부터 2016년 4월까지국립암센터에서과립구수혈치료를받은 25명의호중구감소증환자의자료를후향적으로분석하였다. - 254 -
이세나외 : 효과적인과립구수혈 수혈후절대호중구수가 1,000/ L 이상인회복군과 그렇지못한비회복군두군으로나누어비교분석하였고, 수혈과관련된부작용도분석하였다. 결과 : 과립구성분채집술과과립구수혈치료는총 99건에서시행되었다. 21명 (84%) 의환자에서과립구수혈치료후절대호중구수치가회복되었고, 반면 4명 (16%) 의환자는수혈치료에회복을보이지않았다. 이들두군간에호중구수치회복과관련된변수를분석한결과, 과립구수혈전절대호중구수 (29/ L vs. 0/ L, P=0.048), 과립구수혈치료전호중구감소증의기간 (11일 vs. 26일, P=0.011) 및과립구수혈치료횟수 (2회 vs. 11회, P=0.049) 에서두군간에유의한차이를보였다. 과립구수혈치료중 7명 (28%) 의환자에서일시적인수혈과관련된임상증상의변화를보였으나처치후모든환자가임상적개선을보였다. 1회수혈된과립구용적의중앙값은 220 ml로포함된과립구수는평균 4.92 10 10 개이었다. 결론 : 과립구수혈치료는호중구감소증환자의 감염치료에안전적, 효과적이며치료효과를높이기위해조기의과립구수혈치료가권장된다. References 1. Dale DC, Boxer LA. Guidelines for pediatric management of severe chronic neutropenia. Am J Hematol 2012;87:133 2. Penack O, Becker C, Buchheidt D, Christopeit M, Kiehl M, von Lilienfeld-Toal M, et al. Management of sepsis in neutropenic patients: 2014 updated guidelines from the Infectious Diseases Working Party of the German Society of Hematology and Medical Oncology (AGIHO). Ann Hematol 2014;93:1083-95 3. Cancelas JA. Granulocyte : questions remain. Blood 2015;126:2082-3 4. Strauss RG. Role of granulocyte/neutrophil s for haematology/oncology patients in the modern era. Br J Haematol 2012;158: 299-306 5. Díaz R, Soundar E, Hartman SK, Dreyer Z, Teruya J, Hui SK. Granulocyte s for children with infection and neutropenia or granulocyte dysfunction. Pediatr Hematol Oncol 2014;31:425-34 6. Ofran Y, Avivi I, Oliven A, Oren I, Zuckerman T, Bonstein L, et al. Granulocyte s for neutropenic patients with life-threatening infections: a single centre experience in 47 patients, who received 348 granulocyte s. Vox Sang 2007;93:363-9 7. Worel N, Kurz M, Peters C, Höcker P. Serial granulocytapheresisunder daily administration of rhug-csf: effects on peripheral blood counts, collection efficiency, and yield. Transfusion 2001;41:390-5 8. Ministry of Health and Welfare. The administration law of blood management. Sejong: Ministry of Health and Welfare, 2016 9. Brockmann F, Kramer M, Bornhäuser M, Ehninger G, Hölig K. Efficacy and side effects of granulocyte collection in healthy donors. Transfus Med Hemother 2013;40:258-64 10. Price TH, Boeckh M, Harrison RW, McCullough J, Ness PM, Strauss RG, et al. Efficacy of with granulocytes from G-CSF/dexamethasone-treated donors in neutropenic patients with infection. Blood 2015;126:2153-61 11. Lee JJ, Chung IJ, Park MR, Kook H, Hwang TJ, Ryang DW, et al. Clinical efficacy of granulocyte therapy in patients with neutropenia-related infections. Leukemia 2001; 15:203-7 12. Estcourt LJ, Stanworth SJ, Hopewell S, Doree C, Trivella M, Massey E. Granulocyte s for treating infections in people with ne- - 255 -
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