각종 난치성 혈액 질환에서의 비혈연간 골수이식

김동욱,한훈,김정아,김희제,민창기,엄현석,최정현,이종욱,한치화,홍영선,최일봉,신완식,민우성,김학기,김춘추,김원일,김동집 대한조혈모세포이식학회 1997 대한조혈모세포이식학회지 Vol.2 No.1

목적: 비혈연간 골수이식은 혈연내에 적절한 골수공여자가 없는 만성골수성백혈병, 고위험군의 급성별혁병, 면역억제치료에 실패한 재생불량성빈혈 및 각종 난치성 조혈모세포질환의 완치를 위한 표준적인 치료방법으로 정착되고 있다. 혈연간 표준적인 동종 이식에 비하여 비혈연간 이식시에는 생착부전, 이식편대숙주반응과 감염이 더 빈번하게 발생하며, 국내에서는 아직까지 체계적인 임상연구결과가 보고된 바 없었다. 이에 본 센터에서는 1995년 10월 이후로 약 20개월간 26예의 비혈연간 골수이식을 시행하였으며 3개월 이상의 추적관찰이 가능하여 이식초기 합병증의 관찰 및 분석이 가능하였던 20예의 환자를 대상으로 이식성적 및 문제점을 보고함으로써 새롭게 확대되고 있는 이 분야의 임상연구 및 진료의 활성화를 꾀하고자 한다. 방법: 각종 혈액 종양질환으로 비혈연간 이식을 시행한 총 26예의 환자중 3개월이상의 추적관찰이 가능하였던 20예를 대상으로 후향적으로 임상경과를 분석한 후 생존 분석을 시행하였고, 환자의 연령, 성별, 질병의 상태, 조식 적합 항원의 일치정도, 이식편대 숙주 반응의 유무와 생존기간과의 상관관계를 살펴보았다. 또한 표준위험군과 고위험군으로 나누어 생존율을 비교하였고 이식과 관계된 생착 부전, 이식편대숙주반응, 감염의 발생과 양상 그리고 그 합병증을 관찰하였다. 결과: 1. 환자와 공여자간에 HLA 불일치가 20예 중 4예에서 있었으며, 생착여부의 확인이 가능했던 17예 중 16예에서 생착이 확인되어 94.1%의 생착율을 보였다. 2. 급성이식편대숙주반응은 62.5%(10/16예)에서 발생하였으며 111도 이상의 급성의 이식편대숙주 반응은 25%(4/16예)에서 발생하였다. 만성이식편대숙주반응은 40%(2/5예)의 환자에서 발생하였으며 이들 모두 국소형으로 중증의 진행형 만성이식편대숙주반응이 관찰된 환자는 없었다. 3. 호흡기 합병증은 10예(50%)에서 발생하였으며 감염성 폐렴을 포함한 호흡기 합병증이 가장 흔한 일차적인 사망 원인이었다. 호흡기 합병증이 발생했던 10예중 6예가 감염에 의한 폐렴이 의심되었고 나머지 4예는 특발성 간질성 폐렴이었다. 4. 8.5개월의 중앙추적기간 중 35%의 생존율을 관찰할 수 있었고, 생존기간은0.5개월에서 15개월 (중앙치:4개월)이었다. 한편 고위험군은 25%(3/12예), 표준위험군은 50%(4/8)의 생존율을 관찰할 수 있었다. 5. 가장 흔한 사망 원인은 감염성 폐렴을 포함한 호흡기 합병증(6예)이었고, 이외의 사망 원인으로는 급성 이식편대숙주반응과 다장기부전이 각각 2예, 생착 부전, 간정맥 폐쇄, 그리고 재발이 각각 1예였다. Unrelated bone marrow transplantation(UBMT) has been increasingly recognized as the standard treatment for cure of chronic myelogenous leukemia, high risk acute leukemia, aplastic failed on immunotherapy, and the variety of refractory hematologic diseases in patients lacking a related donor. However, as compared to HLA identical sibing transplantation, UBMT carries higher incidence of graft failure, graft versus host disease(GVHD), and infection. In our center, 26 patients underwent UMBT between October 1995 and June 1997. The minimum follow-up of 3 months was possible in 20 patients, for whom early complications and clinical outcomes were assessed. The median age of the 20 patients was 24 years. 8 patients had standard risk disease and 12 patients had high risk disease. All patients received various preparative regimens including total body irradiation according to disease and disease status. 19 patients received CsA + short course MTX for GVHD prophylaxis. One patient received marrow that was depleted of T cells ex vivo using avidinbiotin column. The class I loci were typed by serological methods and HLA-A, HLA-B and HLA-DRB1. 3 additional pairs were one minor mismatched at the HLA-B locus. Another one patients was one major mismatched at the DRBI alleles. 17 patients were evaluable for engraftment. Successful enfraftment was confirmed in 16 patients(94.1%). Only one patient who was performed one major DRBI mismatched transplants experienced graft rejection. 16 patients were evaluable for acute GVHD. The overall incidence of acute GVHD developed in 4 patients(25%). Five patients were evaluable for the development of Ⅳ acute GVHD developed in 4 patients (25%). Five patients were evaluanle for the development of chronic GVHD. 2 patients(40%) developed limited chronic GVHD. Respiratory complications including pulmonary infection developed in 10 patients(50%) and these complications were the most common primary cause of death. Of these 10patients, 6 had pneumonia due to fungus(4 patients), pacterial (1 patient), and CMV infection (1 patient) and 4(20%) had idiopathic interstitial pneumonitis and/or adult respiratory distress syndrome. The duration of median follow- up was 8.5 months and 7 of 20 patients(35%) are alive at the time of this analysis with survival duration of 0.5 to 15 months(median survival duration: 4 months). The overall survival was 25% (3/12 patients) in high risk group and 50%(4/8 patients) in standard group. From these results, we can predict that the incidence and severity of GVHD in Korea are lesser than multiracial countries and the long-term survival of patients with standard risk disease can approach that of HLA matched sibling transplants. For the past two years, the performance of UBMT has been rapidly increasing and it will be possible to analyze much larger number of patients soon in Korea. In the future the problems of graft failure, GVHD, and infection due to long lasting immunocompromised status will need to be overcome by continued medical research. In addition, the volunteer donor pool will have to be expanded by the promotion of the national awareness of its need.

저골수 충실성 급성 골수성 백혈병의 치료방침 화학 요법과 골수이식

김영균(Young Kyoon Kim),노진탁(Jin Tark Nho),박은영(Eun Young Park),한치화(Chi Wha Han),박종원(Chong Won Park),김춘추(Choon Choo Kim),김동집(Dong Jip Kim),한경자(Kyung Ja Han),김원일(Won Il Kim) 대한내과학회 1988 대한내과학회지 Vol.35 No.6

N/A There have been a few repots of acute myelogenous leukemia (AML) presenting hypocellular bone marrow. Most physicians are reluctant to give these patients intensive chemotherapy because of the potential risk of serious bone marrow failure. We experienced 10 patients with hypocellular AML (HAML) that could be difined by the criteria of 30% or more atypical blasts and 50% or less cellularity in the bone marrow. There were six men and four women and their ages ranged from 20 to 67 years. Various regimens including low dose ara-C alone (4 cases) and low dose ara-C with modified TAD (1case), with mitoxanthrone (1 case) or with mithramycin (1 case) were applied. Of the remaming three patlents; one received supportive care only, another mithramycin alone and the third allogeneic bone marrow transplantation. As a result, the three cases who received either allogeneic bone marrow transplantation or low dose ara-C with modified TAD or that with mitoxanthrone entered into complete remission. However, only the patient who received allogeneic bone marrow transplantation is still alive. The duration of survival ranged from 2 months to 18 months; the median was 8 months. One of the most common complications during chemotherapy was severe bone marrow suppression and the major cause of death was various severe infections during the pancytopenic period. Though the most favorable therapy for HAML is still controversial, bone marrow transplantation is considered to be the choice of treatment at the present time for young patients with HLA-identical donors. If bone marrow transplantation is not available, a more aggressive form of therapy in addition to low dose ara-C will be preferable.

류마티양 관절염 32 예의 임상적 고찰

김동집 ( Dong Jip Kim ),김기호 ( Ki Ho Kim ),김영 ( Young Kim ),민병석 ( Byong Sok Min ),유재영 ( Jai Young Yoo ),김춘추 ( Choon Choo Kim ),최두혁 ( Du Hyuk Choi ) 대한내과학회 1974 대한내과학회지 Vol.17 No.3

중증 재생불량성 빈혈에서 항임파구 항체들의 임상 응용 - 치료 효과

김동집 ( Dong Jip Kim ),김영진 ( Young Jin Kim ),김춘추 ( Choon Choo Kim ),김원일 ( Won Il Kim ),박종원 ( Chong Won Park ),조철수 ( Chul Soo Cho ),박석영 ( Suk Young Park ),박상수 ( Sang Soo Park ),전성주 ( Sung Joo Chun ),한경자 대한내과학회 1985 대한내과학회지 Vol.29 No.4

급성 골수성 백혈병의 관해유도제가 동종 조혈모세포 이식후에 미치는 영향

김희제,이종욱,김기원,박수정,서정곤,민창기,엄현석,홍영선,최일봉,민우성,신완식,김춘추,김원일,김동집 대한조혈모세포이식학회 1998 대한조혈모세포이식학회지 Vol.3 No.2

연구배경: 급성 골수성 백혈병 환자에서 관해유도 치료제로 관해유도후 동종 조혈모세포이식을 시행한 경우에 관해유도제의 종류가 이식후 장기 무병생존율에 미치는 영향들을 분석하고자 하였다. 방법: 가톨릭 조혈모세포 이식센타에서 1984년 6월부터 1997년 9월까지 급성 골수성 백혈병으로 처음으로 진단받고 세가지(TAD, TIA, TIB) 주된 관해유도요법에 따라 치료받은 환자들 중에서 골수검사 결과 및 임상적으로 완전 관해상태에서 동종 조혈모세포이식을 시행받은 56명의 이식성적을 분석하였다. 전체 56명의 대상환자들중 TAD(A군) 치료가 12명, TIA(B군) 치료가 12명이었고 TIB(C군) 치료가 32명이었다. 완전관해 유도를 위해서 처음 7일간의 항암제 투여후 7일째 골수 검사를 시행하여 필요한 경우 본 센타의 기준에 따라 3일간의 부가적 강화화학요법제 치료를 시행하였다. 최대 10일간의 1차 치료에 실패한 경우에는 혈액학적 소견이 회복된수 재차 본 센타의 치료지침에 따른 다양한 2차 관해유도요법을 시행하였으며 관해상태에서 후속 공고요법은 본 센타의 표준치료계획에 따라 0~3회까지 다양하게 시행되었다. 동종 조혈모세포이식 전처치요법으로는 통상의 'TBI+ Cyclophosphamide'와 'Busulfan+Cyclophosphamide'를 사용하였으며 무병 생존율에 미치는 영향인자들을 통계분석하였다. 결 과: 1. 관해 유도요법으로 3×10만으로 완전 관해상태에 이르러 이식한 경우가 21명(37.5%)이었고 C군에서는 5명이 3×10 요법으로도 관해유도에 실패하여 2차 관해유도요법이 필요하였던 경우였다. 각군간에 FAB 형분포, 이식전 공고요법의 횟수, 관해후 이식까지의 기간등은 차이가 없었다. 2. 전체 56명 환자를 이식후 중앙값 26개월(3~123)동안 추적 관찰한 결과 2년간 무병생존율은 A, B, 그리고 C군에서 각각 75%, 67,1%, 그리고 66.7%였다. 세군간에 생존율의 통계적 의의는 없었다(p= 0.8168). B군과 C군과의 비교에서도 통계학적으로는 의의있는 결과는 발견되지 않았다(p=0.5368). A, B, 그리고 C군에서 무병 생존기간의 중앙값은 각각 84.3개월(6~123), 39.3개월(3~53), 그리고 18개월(6~43) 이었다. 3. A, B, C군별로 급성 이식편대 숙주반응 발생 빈도는 0~1도가 각각 10명, 8명, 30명이었고 2도 이상은 각각 2명, 4명, 3명이었다. 2도 이상의 급성 이식편대 숙주반응 발생률은 15.7%(9/57)였다. 만성 이식편대 숙주반응 발생 빈도는 국한성이 A군 3명, C군 2명이었으며 평가 가능한 대상 환자중 국한성 만성 이식편대 숙주반응은 25%(14/56)였고, 범발성은 10.7%(6/56)의 빈도를 보였다. 사망 원인을 보면 A군에서는 재발 2명, 범발성만성 이식편대 숙주반응 1명, B군은 범발성 만성 이식편대 숙주반응 2명, 3도 급성 이식편대 숙주반응 1명, CMV 폐렴 1명, 재발 1명이었고 C군은 3도 급성 이식편대 숙주반응 1명, 범발성 만성 이식편대 숙주반응 2명, 재발 4명이 있었다. 각 군간의 재발률 비교에서는 통계적인 의의는 없었다. 4. 전체 56명에 대한 무병 생존율에 영향을 미치는 인자를 분석한 결과 남녀 성차이, 나이, FAB아형, 급, 만성 이식편대 숙주반응 발생유무, 공고요법의 횟수, 완전관해 유도후 이식까지 소요된 시간, 관해유도치료시 3×7만으로 완전관해에 이른 군(n=21)과 3×10후(n=30), 그리고 2차 관해유도요법후 완전관해에 도달한 군(n=5)간의 이식후 무병 생존율차이 등은 모두 통계학적인 의의가 없었으나 2도 이상의 급성 이식편대 숙주반응 발생시(p=0.0012)와 이식전처치요법에 따른 영향에 대한 단변량분석 결과 (p=0.0292)만이 통계학적인 의의가 있는 인자들로 나타났다. 그러나 다변량 분석 결과 의의있는 인자는 발견할 수 없었다. 결론: 저자들은 처음 치료받는 급성 골수성 백혈병 환자들에서 세가지 종류의 초기 관해유도요법으로 완전관해를 이루고 이후 계획된 동종 조혈모세포이식을 시행한 경우들을 대상으로 이식 이후의 각군의 무병생존율 및 재발률을 분석하였으나 통계적으로 유의한 결과를 보이지 않았다. 따라서 일차관해시의 관해유도제의 종류와 이식후 장기생존율과의 의의 있는 상관관계는 없다고 생각된다. Background: To evaluate the outcome after allogeneic stem cell transplantation (allo-SCT) according to the remission induction chemotherapy, we analysed results of the three types of induction chemotherapy including Ara-C+daunorubicin(group A), Ara-C+idarubicin(group B), and BHAC+idarubicin(group C) for patients with acute myelogenous leukemia(AML) in first remission. Methods: Fifty-six AML patients were enrolled between June 1984 and September 1997. The median age was 33 years(range, 15 to 45). The remission induction therapy consisted of daunorubicin(D1-D3)+Ara-C(D1-D7) in group A(n=12), idarubicin(D1-D3)+Ara-C(D1-D7) in group B(n=12), idarubicin(D1-D3)+BHAC(D1-D7) in group C(n=32) and the augmentation were added based upon the results of bone marrow study on seventh-day(D7) of induction chemotherapy by residual leukemic blast percent. Conditioning regimens for SCT included total body irradiation(TBI) + cyclophosphamide(n=53) or busulfan+cyclophosphamide(n=3). Graft- versus-host-disease prophylaxis consisted of cyclosporine and short-term methotrexate. Results: Five cases of AML in group C were needed more than one course of induction chemotherapy for achieving complete remission(CR). 56 patients were performed allo-SCT and we compared disease-free survival(DFS) in each group. Probability of DFS at 2 years in group A, B and C showed 75%, 67.1% and 66.7%, respectively with median follow-up of 23 months (3-123)(p=0.8168). Probability of relapse and incidence of acute or chronic GVHD were not statistically significant between three groups. The causes of death after SCT in each group were as following: two relapses and one extensive chronic GVHD in group A, two extensive chronic GVHD, one grade III acute GVHD, one relapse, and one CMV pneumonia in group B, and one grade III acute GVHD, two extensive chronic GVHD, and four relpases in group C. The worst prognostic factor influencing DFS after allo-SCT was the presence of more than grade II acute GVHD in univariate analysis(p=0.0012). Conclusion: Although there was different follow-up period in these three groups, these data indicate that type of induction chemotherapy does not affect the outcome after allo-SCT for patients with AML in first CR.

HBV : O-008 ; Durability after discontinuation of nucleos(t)ide therapy in chronic HBeAg negative hepatitis patients

( Young Jip Kim ),( Soon Sun Kim ),( Da Mi Lee ),( Hyo Jin Lee ),( Miyeon Lee ),( Jae Youn Cheong ),( Sung Won Cho ) 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.1

Background: The ideal treatment duration of HBeAg negative chronic hepatitis B is not well known. Relapse has been reported after stopping NUC therapy in the majority of chronic HBeAg negative hepatitis patients. However APASL guideline suggest that if undetectable HBV-DNA has been documented on three occations 6 months apart, discontinuation of treatment can be considered. We investigate the frequency of relapse rate in HBeAg negative CHB patients receiving NUC therapy. Methods: The NUC therapy was discontinued at least three times undetectable level of HBV DNA leave a 6 months space with in 45 patients. (25 with entecavir, 14 with lamivudine, 6 with adefovir.) All patients had follow up at least 1 year after stopping NUC therapy. They were monitored their symptoms, serum AST, ALT and HBV DNA level. Clinical relapse was defined HBV DNA>2,000IU and at least one of the AST, ALT is more than 2 times of upper limit of that. Virologic relapse was defined only HBV DNA>2,000IU regardless their AST, ALT. Results: Clinical relapse developed in 16 (35.6%) and 24 (53.3%) patients after stopping therapy at 6 months and 12 months off therapy, respectively. Virologic relapse developed 22 (48.9%) and 33 (73.3%) patients at 6 months and 12 months off therapy. The factors such as age, gender, cirrhosis, baseline AST, ALT, HBV DNA levels, treatment duration, and consolidation duration were analyzed to investigate the predictive factors associated with 1year sustained response. Of these factors, baseline HBV DNA (92.3% in those with baseline HBV≥108 copies/ml, 63.3% in HBV<108 copies/ml.) and cirrhosis (86.1% in CHB, 22.2% in LC) were significantly associated with 1 year virologic relapse. Conclusions: Virologic relapse developed in the majority (73.3%) of patients and clinical relapse developed in the half (53.3%) patients at 1 year off therapy. Baseline HBV DNA level (<108 copies/ml) and LC were found associated with the low rate of virologic relapse.

Induction Chemotherapy followed by Radiotherapy in Advanced Head and Neck Cancer

Kim, Dong Jip,Cho, Seung Ho,Moon, Hanlim,Lee, Kyung Shik,Yoon, Sei Chul,Kim, Min Sik,Hong, Young Seon,Kim, Hoon Kyo,Oh, Yoon Kyung,Suh, Byung Do CATHOLIC MEDICAL CENTER 1988 Bulletin of the Clinical Research Institute Vol.16/17 No.1

Untreated patients with head and neck cancer without distant metastasis underwent the induction chemotherapy followed by radiotherapy. Patient's age was ranged 34-70 (median 54); 7 were Stage Ⅲ, 19 Stage Ⅳ. Chemotherapy consisted of 3 cycles of cisplatin 100 mg/m^2 on day 1, and f-fluorouracil 1,000 mg/m^2/day for 5 days, every 3 or 4 weeks. Of 26 chemotherapy patients, 22 were evaluable ; complete response was 32% (7/22) and partial response 50% (11/22). Seventeen Patients completed radiotherapy following chemotherapy; complete response was 58.8% (10/17) and partial response 23.5% (4/17), The toxicities were tolerable. The induction chemotherapy using cisplatin and f-fluorouracil followed by radiotherapy was safe and effective.

Original Article : Durability after discontinuation of nucleos(t)ide therapy in chronic HBeAg negative hepatitis patients

( Young Jip Kim ),( Ki Chan Kim ),( Sun Hyuk Hwang ),( Soon Sun Kim ),( Dami Lee ),( Jae Youn Cheong ),( Sung Won Cho ) 대한간학회 2013 Clinical and Molecular Hepatology(대한간학회지) Vol.19 No.3

Background/Aims: Relapse has been reported after stopping nucleos(t)ide (NUC) therapy in the majority of chronic HBeAg negative hepatitis patients. However, the ideal treatment duration of HBeAg negative chronic hepatitis B (CHB) is not well known. We investigated the frequency of relapse in HBeAg negative CHB patients receiving NUC therapy. Methods: The NUC therapy was discontinued at least 3 times undetectable level of HBV DNA leave 6 months space in 45 patients. Clinical relapse was defined as HBV DNA >2,000 IU/mL and alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 times of upper limit of normal range. Virological relapse was defined as HBV DNA >2,000 IU/mL. Results: Clinical relapse developed in 16 (35.6%) and 24 (53.3%) patients after stopping therapy at 6 months and 12 months off therapy, respectively. Virological relapse developed 22 (48.9%) and 33 (73.3%) patients at 6 months and 12 months off therapy. The factors such as age, gender, cirrhosis, baseline AST, ALT, HBV DNA levels, treatment duration, and consolidation duration were analyzed to investigate the predictive factors associated with 1 year sustained response. Of these factors, cirrhosis (86.1% in CHB, 22.2% in LC) was significantly associated with 1 year virological relapse rate. Baseline HBV DNA and total treatment duration tended to be associated with virological relapse. Conclusions: Virological relapse developed in the majority (73.3%) of HBeAg negative CHB patients and clinical relapse developed in the half (53.3%) of patients at 1 year off therapy. Cirrhosis may be associated with the low rate of virological relapse. (Clin Mol HepatoI2013;19:300-307)

급성백혈병 치료시 흔치 않은 합병증들

김영진,조철수,한치화,홍영선,문한림,김춘추,김동집 大韓血液學會 1984 大韓血液學會誌 Vol.19 No.2

HBV : O-008 ; Durability after discontinuation of nucleos(t)ide therapy in chronic HBeAg negative hepatitis patients

( Young Jip Kim ),( Soon Sun Kim ),( Da Mi Lee ),( Hyo Jin Lee ),( Mi Yeon Lee ),( Jae Youn Cheong ),( Sung Won Cho ) 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.-

Background: The ideal treatment duration of HBeAg negative chronic hepatitis B is not well known. Relapse has been reported after stopping NUC therapy in the majority of chronic HBeAg negative hepatitis patients. However APASL guideline suggest that if undetectable HBV-DNA has been documented on three occations 6 months apart, discontinuation of treatment can be considered. We investigate the frequency of relapse rate in HBeAg negative CHB patients receiving NUC therapy. Methods: The NUC therapy was discontinued at least three times undetectable level of HBV DNA leave a 6 months space with in 45 patients. (25 with entecavir, 14 with lamivudine, 6 with adefovir.) All patients had follow up at least 1 year after stopping NUC therapy. They were monitored their symptoms, serum AST, ALT and HBV DNA level. Clinical relapse was defined HBV DNA>2,000IU and at least one of the AST, ALT is more than 2 times of upper limit of that. Virologic relapse was defined only HBV DNA>2,000IU regardless their AST, ALT. Results: Clinical relapse developed in 16 (35.6%) and 24 (53.3%) patients after stopping therapy at 6 months and 12 months off therapy, respectively. Virologic relapse developed 22 (48.9%) and 33 (73.3%) patients at 6 months and 12 months off therapy. The factors such as age, gender, cirrhosis, baseline AST, ALT, HBV DNA levels, treatment duration, and consolidation duration were analyzed to investigate the predictive factors associated with 1year sustained response. Of these factors, baseline HBV DNA (92.3% in those with baseline HBV≥108 copies/ml, 63.3% in HBV<108 copies/ml.) and cirrhosis (86.1% in CHB, 22.2% in LC) were significantly associated with 1 year virologic relapse. Conclusions: Virologic relapse developed in the majority (73.3%) of patients and clinical relapse developed in the half (53.3%) patients at 1 year off therapy. Baseline HBV DNA level (<108 copies/ml) and LC were found associated with the low rate of virologic relapse.