미니동종 조혈모세포 이식에서 T림프구 수용체 단클론성 항체의 이용 가능성 및 혼합 림프구 배양에서 림프구 억제효과에 대한 연구

손상균,박성원,백진호,김동환,정진태,현동우,곽동석,이재태,이규보 대한조혈모세포이식학회 1999 대한조혈모세포이식학회지 Vol.4 No.2

연구배경: 조혈모세포이식 및 조건화 치료는 원발성 질환을 제거 후 새로운 조혈세포를 이용한 공간을 마련하고 세포의 생착을 이름으로써 치료의 목표를 달성하고자 하나 심한 부작용으로 인한 높은 조기 사망률은 극복하여야 할 점이다. 저독성 조건화 처치를 하면 불충분한 면역세포의 살해로 인한 거부반응이 큰 문제가 된다. 이에 거부반응 및 이식편대숙주반응의 중요한 역할을 하는 림프구에 대한 억제작용을 갖는 단클로성 항체의 생체 내에서 효과를 추측하기 위해 DLA(Dog lymphocyte Antigen) mismatched dog의 말초혈액을 이용한 MLC assay를 시행하였다. 방법: DLA typing의 결과와 비교하기 위해 단클론성 항체 첨가 없이 DLA가 서로 다른 3마리의 말초혈액을 이용하여 서로의 MLC 반응을 비교 실험하였다. T림프구 수용체에 대한 단클론성 항체의 농도에 따른 proloferation 억제효과를 보기 위해 2, 10, 20, 200ug/ml의 농도로 DM5 (antigranulocyte antbody: 음성 대조군)와 비교하였다. 항원에 감작된 림프구에서의 D5에 대한 효과를 보기위해 장기 골수 배양 배지에서 responder를 stimulator 및 D5와 함께 3일간 배양후 세척하고 2일간의 배양후 다시 stimulator로서 재자극 후 5일 뒤에 proliferation assay를 시행하였다. 실제 이식을 시행한 donor 및 recipient의 세포를 분리하여 proliferation assay를 하여 이식 전후를 비교하였다. 결과: T림프구 수용체에 대한 단클론성 항체의 농도를 달리한 실험에서 2, 10 ,20ug/ml 모두에서 같은 농도의 DM5는 억제효과가 없는데 비해상 당한 림프구증식 억제효과가 관찰되었다. In vivo 실험에서 중용량의 방사성 치료 및 면역 억제 요법으로 DLA matched 2마리 모두에서 성공적인 생착을 확인하였다. 공여자의 mismatched sample에 대해 G-CSF를 이용한 가동화 치료전 보다 낮은 proliferation score를 보였다. 결론: T림프구 수용체에 대한 단클론성 항체는 In vitro 실험에서 T림프구의 억제효과가 관찰되었고 동물 이식에서 부작용을 줄이는 저용량의 조건화 치료 후 생착을 유도하는 면역억제제로서 그 가능성을 확인하였고 향후 그 기전에 대한 연구 및 많은 생체 실험이 필요하다고 생각된다. 재생불량성 빈혈 같은 저세포 충실도의 골수 질환이나 과거에 방사선 치료를 심하게 받은 경우는 이미 골수 내 생착을 위한 공간이 마련된 상태이므로 특별한 면역억제 요법이 가능하다면 이러한 저독성의 조건화 처치가 유용하게 응용될수 있을 것으로 전망된다. Background: The objective of this study was to evaluate the effect of anti-TCR monoclonal antibody in mixed lymphocyte culture and as a part of immunosuppressive regimens in the allogeneic stem cell transplantation. Since marrow space is empty in the patients with aplastic anemia or previous radiation and no new space for allograft needs to be created, nontoxic imminosuppressive conditioning regimens should be feasible. These may include monoclonal antibody directed against T cell receptor other surface determinants on T cell. Moncoclonal antibody (MAb) 15.9D5 raised to canine TCR α β was found to induce hyporesponsiveness to allogeneic stimulator cells in primary and secondary mixed lymphocyte culture (MLC). Methods: Anti-TCR monoclonal antibody was tested to evaluate its suppressive effect of lymphocyte activity in vitro compared with anti- granulocyte anti body and used as an immuno-suppressive agent in two recipient dogs. Four different concentration of anti-TCR MAbs was tested in MLC to know the appropriate concentration for suppressing lymphocyte proliferation, and MLC assays were serially done from blood sample of recipient dogs and donor dogs before and after transplantation. Results: Anti-TCR monoclonal antibody had significantly suppressed H3-thymidine uptake in MLC compared with anti-granulocyte antibody(control). In two recipient dogs conditioned with non-myeloablative regimens and MAb, transplanted with DLA- matched donor dogs, successful mobilizing stem cells were less reactive to the stimulator lymphocytes than the lymphocytes from the dogs not treated before. Conclusion: The precise mechanism of immunosuppression induced by anti- TCR MAb needs to be elucidated. G-CSF had a role in suppressing lymphocyte activity of donor dogs and might have a role in preventing GVHD. Non-myeloablative conditioning strategy might be useful in patients with hypoplastic marrows who require immunosuppression only (e. g. aplastic anemia) and already has some spaces for engraftment in the marrow (e. g. irradiated marrows).

液膜에 의한 廢水중의 重金屬이온의 分離

孫晋彦,李成植,金鍾和,全成均 동아대학교 환경문제연구소 1986 硏究報告 Vol.9 No.1

The purpose of this paper was to separate the copper and nickel ions from waste water using supported liquid membrane The effect of a given amount of carrier and ammonia concentration of up-stream was described. We used the LIX65N as carriers. The results were as follows 1. The distribution ratio of copper ions at equilibrium was shown linear increment according o the mole ratio of carrier concentration versus the concentration of metal ions increased to 2.0. The maximum distribution ratio of copper ions exceeded that of nickel by approximately 4-fold when the liquid membrane was saturated by carrier 2. The important parameters governing flux were carrier and ammonia concentration. We compared these two parameters, and then the latter influenced more than the former to get higher flux. The copper ions reacted with ammonia in the up-stream, it formed a complexes of Cu(NH₃)₄^(2+), and then diffused to interface of liquid membrane. 3. The flux of metal ions were increased with enlarging the distribution ratio of ordinary extraction. The principle of coupled transport was carried out by the difference of concentration of hydrogen ions. 4. We can be selectively separated in the mixing soultion of copper and nickel ions using LIX65N as carrier.

急性特發性心囊炎의 1例

金星潤,孫宜錫,李禎均,許鳳烈,咸駿洙,金鮮宙 대한의학협회 1977 대한의학협회지 Vol.20 No.9

동종 말초혈액 조혈모세포를 이용한 다양한 임상적용에 관한 단일병원 경험보고

채의수,손상균,성우진,서광운,박성원,김종광,정진태,이난영,서장수,이규보 경북대학교 병원 2002 경북대학교병원의학연구소논문집 Vol.6 No.1

배경:동종 말초혈액 조혈모세포 이식은 골수이식에 비해 많은 양의 조혈모세포 및 T―림프구 이식으로 인해 빠른 회복이 가능하며 강력한 이식편대종양반응이 유도될 수 있는 장점이 있어 이를 잘 응용한다면 악성 혈액질환에서 치료율을 높일 수 있을 것으로 사료된다.본 연구에서는 동종 말초혈액 조혈모세포 이식의 장점을 이용한 다양한 임상적용을 소개하고자 한다. 방법:경북대학교병원 조혈모세포 이식센터에서 동종 말초혈액 조혈모세포 이식을 시행한 증례 중에서 동종 골수이식수술에 비해 말초혈액 조혈모세포 이식이 유리할 것으로 생각디는 재발의 가능서이 높은 악성질환에서의 더욱 강력한 이식편대종양반응 유도를 위한 동종 말초혈액 조혈모세포를 이용한 예방적 공여자 림프구주입 등의 임상적용을 시도한 증례 및 결과를 분석하였다. 결과:17례의 재발의 가능성이 높은 고위험군의 악성 혈액질환을 대상으로 한 동종 말초혈액 조혈모세포 이식에서 90일 이내의 치료와 관련된 사망률은 23.5%이었고 중앙 추적기간 563일(범위 120∼926일)간의 무병생존율은 35.3%이었다.CSF로 가동화한 말초혈액 조혈모세포를 추가적으로 수혈받은 환자 7명 중 4명(57.1%)이 중앙 추적기간 538일(범위120∼926일)째에 완전관해 상태로 생존 중에 있다.그 외 말초혈액 조혈모세포를 아용한 미니 이식,동종 말초혈액 조혈모세포를 이용한 예방적 stepwise dose-increment 공여자 림프구주입술 등을 시행한 증례에서 장기 생존의 결과를 보여주고 있다. 결론:동종 말초혈액 조혈모세포 이식은 많은 양의 조혈모세포 및 T-림프구의함유로 인해 높은 생착률과 빠른 회복,강력한 이식편대종양반응 등이 유도되는 장점이 있으므로 기존의 골수이식술에 비해 보다 광범위한 임상적용이 가능하리라 사료된다. Background: It is apparent that more stem cells can be harvested by mobilization treatment with recombinant human G-CSF and/or GM-CSF from normal healthy donors in allogeneic peripheral biood stem celltransplantation(allo-PBSCT) compared to allogeneic bone marrow transplantation(allo-BMT).It is also known to be more effective in inducing the graft-vs-tumor affects than allogeneic BMT because of higher T cell content. Methods: A variety of clinical applications with allo-PBSCT was done for patients with hematoligical malignancies with a high risk of relapse in sigle transplantation center. We reported the preliminary results on trial of allo-PBSCT followed by planned prophyactic G-and/or GM-CSF primed donor lymphyocyte infusion additionally reserved at harvest in hematological malignancies with a high risk of relapse and also presented the successful trial of non-myeloablative transplantation for old aged AML paient in 4th complete remission and cases with 2nd transplantation with allo-PBSCs. Results: Seventeen patients with hematological malignancies with a high risk of relapse were enrolled in trial of allo-PBSCT followed by prophylactic donor lymphocyte infysion.All patients received allogeneic PBSCT from HLA- matched sibling donor.Aeven out of 17 patients recived additional PBSCs with a median number of CD3+ CELLS OF 5.0×10^7/kg(range,3.0 to 9.9×10^7/kg), between day 41 and day 120.Four surving patients(4/7) were free of disease when last assessed(median follow-up duration, 538 days), but were suffering from chronic GVHD(1 limited and 3 extensive). A 56 year old acute myeloid leukemia patient in the 4th complete remission was successfully treated with allo-PBSCT with non-myeloablative conditioning regimen.One of 2 patients who received second transplantation with allo-PBSCT has shown a long term disease free survival. Conclusion: A merit of allo-PBSCT would allow us to design a variety of clinical applications. Allo-PBSCT might be preferable in special clinical setting such as non-myeloablative transplantation, second transplantation,or the situation in need of the strong GVL effect. And also CSF-primed PBSCs can be used for the purpose of donor lymphocyte infusion.(korean J Hematol 2001;36:214~222)

급성백혈병의 화학요법에서 조혈간세포 보충요법

이규보,배선근,손상균,이재태,이건수,이경혜,서장수 경북대학교 병원 1997 경북대학교병원의학연구소논문집 Vol.1 No.1

1. 목적 급성백혈병의 화학요법에 있어서 관해유도 요법시에 보다 더 강력한 항암화학요법을 시행하고 골수억제의 회복을 위하여 말초혈액에서 채취한 조혈모세포의 투여로 그 효과를 증대시키고자 시도하였다. 2. 방법 관해유도 화학요법후에 골수억제시기로부터 회복단계로서 백혈구감소증이 호전도면서 단핵세포가 증가될 때에 말초혈액에서 조혈간세포(stem cell)로 인정되고 있는 CD34+세포의 함유량이 1% 이상되는 시기를 찾아내고 그 때부터 평균 4차례의 단핵구를 분리채집을 하여 -74。C에 냉동보관하였다가 제2차 화학요법후에 해동시켜서 정맥주입하였다. 3. 결과 대상 급성백혈병환자는 6명에 23회의 조혈간세포를 함유한 단핵구 채집을 시행하였고 유효한 단핵구의 채집은 4례에서 가능하였고 2례에서는 유효한 채집이 못되었다. 채집효율은 39.0-74.5%로서 평균 49.8%였다. 채집 후에 혈액학적 변화는 혈색소의 약간 감소 (평균 1.34g/dl)와 혈소판의 감소 (평균20.25%)를 나타내었다. 해동 단핵구를 투여할시에 일과성인 불쾌감, 기침, 흉부압박감, 호흡곤란 등이 있었다. 4. 결론 자가골수이식에서 자기말초혈액조혈간세포이식으로 관심이 이행되는 현시점에 자가조혈간세포를 채집하여 수혈하는 기술이 확립되는 기초를 이루었다고 본다. 이번 대상들은 재발된 금성백혈병들에 시행하였으나, 향후에는 초발시에 제일차 관해유도 화학요법 과정에 시도해야할 것으로 생각한다. Object: Peripheral blood stem cells(PBSC) were collected after remission induction chemotherapy and reinfused after intensified chemotherapy in order to increase the chemotherapeutic efficacy. Method: Collection of mononuclear cells (MNC) was started when CD34+ cells above 1% and WBC above 1,000/ul with mononuclear cell percentage above 30%, the collection procedures were done 2-6 time in each patient of total 6 cases. The collected MNCs were stored in - 750C and reinfused after thawing in the water bath at 370C Results: Twenty three collection procedures from the 6 cases of acute leukemia had made effective MNC collection in 4 cases and mean collection efficiency was 49.8%(from 39.0% to 74.5%). Hematological changes after the procedure were mean reduction of hemoglobin 1.34g/dl and mean 20.25% of decreased platelet count. There were noticed transient symptoms of discomfort, coughing, chest tightness and dyspnea in association with the infusion of stored cells. Conclusion: The basic process for the peripheral blood stem cell transplantation (PBSCT) was accomplished with this supportive care for the consolidation chemotherapy of acute leukemia. Effective PBSCT would be warrented with more qualified process and high does chemotherapy. (Korean J Blood Transfus 6(2) : 41~47,1995)

순환기 내과로 자문의뢰된 환자의 임상상

황진용,최지용,손상균,조용근,채성철,전재은,박의현 慶北大學校 醫科大學 1996 慶北醫大誌 Vol.37 No.4

목적 : 순환기내과 영역은 많은 과로부터 자문의뢰를 받는 영역으로 알려져 있다. 특히 최근 우리나라의 순환기질환의 유형이 변화되고 입원환자가 고령화되면서 동반된 심질환의 유병율도 증가하고있다. 이에 저자들은 타과로 입원하여 순환기내과로 자문의뢰되는 환자의 임상상과 3차병원인 경북대학교병원에서의 순환기내과자문의 유용성 등을 평가하여 향후 순환기질병에 대한 협의진료에 도움을 주고자 본 연구를 시행하였다. 방법 : 1995년 3월부터 순환기내과로 공식자문의뢰된 첫 100명을 대상으로 전향적으로 연령, 의뢰이유, 최종진단명, 수술과의 관련성 여부, 순환기내과의 최종조치, 타과의 순응도 등을 조사하였다. 결과 : 1) 자문을 의뢰한 환자는 평균 58±16(15-89, 중앙치 61)세였고 60세이상의 환자가 57%로 고령의 환자가 많았다. 2) 내과계열 25%, 외과계열 75%로 외과계열의 자문이 많았고 일반외과가 26%로 가장 많았고 내과의 다른 분과가 12%, 신경외과 12%, 정형외과 11%, 흉부외과 11%, 신경과 11% 등의 순이었다. 외과계열중 수술을 시행한 경우는 58례로 이중 응급수술이 13례였다. 술전 위험도 평가를 위한 자문이 38례에서 있었는데 순환기적인 문제로 수술을 받지 못한 경우는 2례(1례는 허혈성 심질환, 1례는 심낭질환)이었다. 이때 응급수술을 제외한 입원일과 술전 자문일파의 간격은 평균 3±7일(입원일-42일)이고 술전 자문일과 수술일과의 간격은 평균 6±4일(1-16일)이었다. 3) 타과의 의뢰이유는 심전도 이상이 36례, 높게 측정된 혈압이 20례, 순환기질환의 과거력 17례, 환자의 증상 때문인 경우가 10례였고 심전도의 이상중에는 부정맥이 18례, 이상 Q파 6례, ST절 이상이 5례, 각차단이 3례의 순이었다. 순환기과거력 중에는 허혈성 심질환이 6례, 현재 혈압은 정상이나 고혈압의 과거력이 있는 경우가 4례 순이었고 환자의 증상은 흉통 6례, 호흡곤란이 3례, 기절이 1례였다. 4) 자문후 최종진단이 가능했던 91례를 진단별(총 97 진단명)로 나누어 보면 고혈압이 28례, 부정맥이 16례, 허혈성 심질환이 14례, 판막질환이 11례, 순환기질환이 아닌경우가 19래였다. 이들중 추적진료가 필요하다고 응답한 경우가 57례였으나 순환기내과 외래에 1번이상 추적진료한 경우는 32례(56%)로 환자의 순응도는 낮았다. 결론 : 순환기내과의 자문의뢰는 고령자에게 많았고 수술과 관련된 경우가 많았으며 심전도의 이상이 의뢰이유로 가장 많았으며 진단별로는 고혈압과 부정맥이 가장 많았다. 그리고 순환기적인문제로 수술을 받지 못한 경우는 드물었고 자문후 지속적인 추적진료를 위해 환자의 교육이 필요하겠다. Objective : Clinical characteristics of the patients with cardiovascular diseases in the general hospital have been changed and prevalance of co-existing cardiovascular disease in the patients who were admitted for non-cardiac diseases has been increased remarkably as the proportion of elderly patients increased rapidly in Korea. We evaluated clinical features of the patients consulted for cardiological evaluation and effectiveness of the consultation in the setting of tertiary general hospital, Kyungpook University Hospital. Method : One hundred patients were studied between January 1995 and January 1996. They were evaluated for the reason of consultation, final diagnosis, final recommendation from cardiologists and its impact on the management of the patients, and compliance of the consulting departments. Results : 1) The ages ranged between 15 and 89 (mean 58±16, median 61) years, 57 patients were male and 43 female. Fifty seven patients were older than 60 years. 2) Consultations from surgical parts were 75 patients. Consultation from general surgery was most frequent (26%), followed by other divisions of internal medicine (12%), neurosurgery (12%) and orthopedic surgery (11%), chest surgery (11%), neurology (11%), obstetrics and gynecology (8%), urology (4%), ophthalmology (2%), dermatology (2%), ENT (1%). Among 75 patients from surgical parts, operation was done on 58 patients, including 13 emergency cases. Preoperative cardiac risk evaluation was the reason of consultation in thirty eight patients, of which operation could not be done in only 2 patients (one had severe ischemic heart disease, the other large pericardial disease). Interval between consultation day and operation day was 6±4 days (1-6 days). 3) Reasons for cardiac consultation were electrocardiographic (ECG) abnormalities in 36 patients, high blood pressure in 20 patients, previous cardiovascular diseases in 17 patients, symptoms of the patients in 10 patients. Among EGG abnormalities, arrhythmias was the reason in 18 patients, abnormal Q waves in 6 patients, ST-T segment abnormalities in 5 patients, bundle branch block in 3 patients. Among previous cardiovascular disease, presence of ischemic heart disease was the reason in 6 patients, previous hypertension in 4 patients. Chest pain was the reason of the consultation in 6 patients, dyspnea in 3 patients, syncope in 1 patient. 4) Definite diagnoses could be made in 91 patients with 96 diagnoses which were hypertension and its complications in 28, arrhythmia with underlying disease in 16, ischemic heart disease in 14. valvular heart disease in 11, non-cardiovascular disease in 19. Cardiological follow up was recommended in 57 patients. However, 25 patients (44%) were lost to follow-up. Conclusion : Cardiological consultation was frequent in the elderly patients. Most frequent reason for consultation was EGG abnormalities. Hypertension or arrhythmia was most common final diagnosis. Inoperability due to cardiovascular problems were rare.

Survey of experts on therapeutic policies and proposals for the optimal timing for allogeneic peripheral blood stem cell transplantation in transfusion-dependent patients with myelodysplastic syndrome-refractory anemia

Sang Kyun Sohn,Joon Ho Moon,Yoo Jin Lee,Sung Woo Park,Ji Yoon Kim 대한혈액학회 2016 Blood Research Vol.51 No.1

BackgroundMost hypomethylating agent (HMA) responders with myelodysplastic syndrome (MDS) eventually need allogeneic stem cell transplantation (SCT) because they often acquire re-sistance to HMAs within two years of treatment. Considering the nature of MDS and the poor outcomes of SCT when performed after confirming the progression of MDS to acute myeloid leukemia (AML), allogeneic SCT should be performed with caution in patients with low-risk MDS.MethodsTo address low-risk MDS, the Korean AML/MDS working party group designed a survey for 34 MDS experts in Korea on therapeutic HMA and allogeneic SCT policies for low-risk MDS. The level of consensus was defined as the percentage of agreement among the experts.ResultsWith regard to the optimal time for allogeneic SCT for HMA responders with MDS-RA, 76% experts agreed that allogeneic SCT should be performed when a patient has a low platelet count. With regard to the relapse pattern that was most commonly found during HMA treatment in responding patients with MDS-RA, 54% experts agreed that the most common pattern that indicated HMA failure was the gradual worsening of cytopenia. ConclusionThe optimal time to perform allogeneic SCT in RA patients who achieved hematologic complete remission during HMA treatment is when the platelet count decreases. However, these suggestions need to be evaluated in larger future studies. Therefore, care-ful decisions should be taken at each step of allogeneic SCT to maximize the outcomes for patients with MDS-RA and iron overload.

Case Reports : Pancytopenic Prodrome ( pre - ALL ) of Acute Lymphoblastic Leukemia in Adults ; Possible Pathogenesis

Sang Kyun Sohn,Jang Soo Suh,Jae Tae Lee,Kyu Bo Lee 대한내과학회 1998 The Korean Journal of Internal Medicine Vol.13 No.1

We report two cases of adult acute lymphoblastic leukemia presenting with preleukemic phase of pancytopenia with a few abnormal lymphoid cells in bone marrow aspirates. The initial diagnosis of each case was suspicious aplastic anemia and hypo- plastic ane

Phase II Study of Cyclophosphamide,Epirubicin,Vincristine, Prednisone,and Etoposide (CEOP-E)for Aggressive Non-Hodgkin 's Lymphoma

Sohn Sang Kyun,Baek Jin Ho,Lee Kyu Bo,Kim Dong Hwan,Park Tae In,Kim Jong Gwang 대한의학회 2004 Journal of Korean medical science Vol.19 No.6

Survey of experts on therapeutic policies and proposals for the optimal timing for allogeneic peripheral blood stem cell transplantation in transfusion-dependent patients with myelodysplastic syndrome-refractory anemia

Sang Kyun Sohn,Joon Ho Moon,Yoo Jin Lee,Sung Woo Park,Ji Yoon Kim 대한혈액학회 2016 Blood Research Vol.51 No.1

BackgroundMost hypomethylating agent (HMA) responders with myelodysplastic syndrome (MDS) eventually need allogeneic stem cell transplantation (SCT) because they often acquire re-sistance to HMAs within two years of treatment. Considering the nature of MDS and the poor outcomes of SCT when performed after confirming the progression of MDS to acute myeloid leukemia (AML), allogeneic SCT should be performed with caution in patients with low-risk MDS.MethodsTo address low-risk MDS, the Korean AML/MDS working party group designed a survey for 34 MDS experts in Korea on therapeutic HMA and allogeneic SCT policies for low-risk MDS. The level of consensus was defined as the percentage of agreement among the experts.ResultsWith regard to the optimal time for allogeneic SCT for HMA responders with MDS-RA, 76% experts agreed that allogeneic SCT should be performed when a patient has a low platelet count. With regard to the relapse pattern that was most commonly found during HMA treatment in responding patients with MDS-RA, 54% experts agreed that the most common pattern that indicated HMA failure was the gradual worsening of cytopenia. ConclusionThe optimal time to perform allogeneic SCT in RA patients who achieved hematologic complete remission during HMA treatment is when the platelet count decreases. However, these suggestions need to be evaluated in larger future studies. Therefore, care-ful decisions should be taken at each step of allogeneic SCT to maximize the outcomes for patients with MDS-RA and iron overload.