초기소견으로 미세혈관병성 용혈성 빈혈상을 보인 골수전이성 악성흑색종 1례

서형찬,민유홍,강웅철,이석,정소영,한지숙,고윤웅,양우익 大韓血液學會 1996 大韓血液學會誌 Vol.31 No.3

노령층 급성 골수성 백혈병에서 관해유도요법후 조혈촉진 인자의 효과

이석,민유홍,서형찬,정소영,한지숙,고윤웅 大韓血液學會 1996 大韓血液學會誌 Vol.31 No.3

NK/T 세포 림프종 환자에서 시행된 비골수제거성 조혈모세포이식

정준원,김진석,장준호,서형찬,이승태,김현옥,양우익,민유홍,한지숙,고윤웅 대한조혈모세포이식학회 2001 대한조혈모세포이식학회지 Vol.6 No.2

저자 등은 맹장, 충수돌기 및 흉막을 침범한 고위험군 NK/T 세포 림프종 환자에서 비골수제거 조혈모세포이식을 시행한 후 이식연관 합병증 없이 무병생존하였기에 보고하는 바이다. NK/T cell lymphoma is a rare type of non-Hodgkin"s lymphomas. It has the histological features of angiocentric lymphoma characterized by prominent angio-invasion by tumor cells, and commonly presents in nasal and paranasal structures. Non-nasal form of NK/T cell lymphoma involves skin, gastrointestinal tract, or liver. With conventional chemotherapy and/or radiotherapy, NK/T cell lymphoma shows poor response rate and seldom results in long term survival. Especially, non-nasal form has more aggressive clinical manifestations and grave outcome than nasal form. We report a case of NK/T cell lymphoma presenting with small bowel perforation and malignant pleural effusion due to lymphoma infiltration, transplanted with allogeneic peripheral blood stem cells from HLA identical sibling donor after fludarabine-based nonmyeloablative chemotherapy. After transplantation, the patient achieved an enduring tri-lineage hematological complete response without any evidence of relapse for 10 months.

동종 조혈모세포이식 후 급성 이식편대 숙주반응 시 T 세포의 OX-40 표현

장준호,정준원,김진석,서형찬,이승태,민유홍,한지숙,고윤웅 대한조혈모세포이식학회 2000 대한조혈모세포이식학회지 Vol.5 No.2

배경:OX-40은 분자량이 50-kD인 당단백으로 최근 활성화되기 시작한 CD 4+ T 세포에 표현된다. 최근 쥐 모델에서 T 세포의 OX-40 표현과 급성 이식편대 숙주반응과의 높은 연관성이 보고되었으나, 아직까지 사람에 있어 급성 이식편대 숙주반응과 T세포의 OX-40 표현간에 의미 있는 연관성을 보고한 연구는 없는 실정이다. 이에 저자는 동종 조혈모세포이식 후 말초 혈액 내 T세포에서의 OX-40 표현을 측정하여 급성 이식편대 숙주반응과의 상관성 등 그 임상적 의의를 평가하고자 본 연구를 시행하였다. 방법:1998년 12월부터 1999년 9월까지 세브란스 병원에서 악성 혈액종양 및 재생불량성 빈혈로 동종 조혈모세포이식을 시행 받은 16예의 환자와 공여자를 대상으로 하였다. 환자들의 말초혈액은 동종 조혈모세포이식 2주전과 이식 후 10일, 17일, 24일째 채취하였다. 공여자의 말초혈액은 이식 2일 전 채취하였다. 세포는 단클론항체로 염색하여 유세포분석기로 분석하였다. OX-40 표현은 유세포분석기를 이용 정량화 하였으며 OX-40+ T 세포가 환자 혹은 공여자의 유래인지를 확인하기 위해 polymerase chain reaction (PCR)을 이용한 variable number of tandem repeats (VNTR) 검사를 시행하였다. 결과: 1) 대상 환자 16예의 평균 연령은 32세(17~50세)였다. 14예의 환자에서 혈연간 동종 조혈모세포이식이 시행되었고, 이 중 12예는 골수이식, 2예에서는 말초 조혈모세포이식을 시행하였다. 2예에서는 비혈연간 동종 조혈모세포이식을 시행하였다. 2) 급성 이식편대 숙주반응이 발생한 6예에서 CD 4+ T 세포의 OX-40 표현율은 평균 33.9±6.8% (22.1~53.2)로 급성 이식편대 숙주반응이 나타나지 않은 환자군에서의 28.2±7.1% (15.2~42.4)와 비교하여 통계학적으로 유의한 차이는 없었으며(p=0.18). 10일, 17일, 24일째에서도 통계학적으로 유의한 차이를 관찰할 수 없었다(p=0.12, p=0.14, p=0.22). 10예의 조혈모세포 공여자의 CD 4+ T세포의 OX-40 표현율은 평균 8.0 ± 4.6% (1.7~16.9%)였다. 3) CD 4+ T 세포의 OX-40 표현 유무 및 그 정도와 급성 이식편대 숙주반응의 중증도와 임상양상과는 유의한 상관관계를 관찰할 수 없었다. 4) 급성 이식편대 숙주반응의 치료에 따른 CD 4+ T 세포의 OX-40 표현 변화는 관찰되지 않았다(p=0.69). 5) 동종 조혈모세포이식 후 환자의 말초혈액에서 시행한 VNTR-PCR 결과 혼합 키메리즘을관찰할 수 있었다. 결론:동종 조혈모세포이식 후 CD 4+ T 세포에서의 OX-40의 표현은 정상인과 동종 조혈모세포이식 전에 측정한 OX-40 표현율과 비교하여 통계학적으로 유의한 상승을 관찰할 수 있었으나 급성 이식편대 숙주반응이 발생한 군에서의 표현율과 급성 이식편대 숙주반응이 나타나지 않았던 군 간에 통계학적으로 유의한 차이를 관찰할 수 없었고 급성 이식편대 숙주반응이 발생한 군에서 치료에 따른 CD 4+ T 세포에서의 OX-40 표현율의 통계학적 유의성을 관찰하지 못하여 동물실험에서와는 달리 급성 이식편대 숙주반응의 예측인자로써 유의한 연관성을 관찰할 수 없었고, 급성 이식편대 숙주반응의 치료를 판정하는 지표로써의 역할에서도 유의한 연관성을 관찰할 수 없었다. Background:Acute GRAFT-VERSUS-HOST disease (GVHD) is a major and often lethal consequence of allogeneic stem cell transplantation. The OX-40 molecule is a 50-kD glycoprotein that is expressed on recently activated CD4+ T cells. Although recently studies in rat model have suggested an close association between OX-40 expression on peripheral blood CD 4+ T cells and course of acute GVHD, there have been few studies in human yet. This study was performed to investigate whether the kinetics of repopulation of T cells in human recipients of HLA-matched allogeneic stem cell transplantation and their OX-40 expression would be predictive of acute GVHD and/or its response to immunosuppressive therapy. Methods:OX-40 expression on T cells was evaluated in 16 patients with hematologic malignancies or aplastic anemias, who received allogeneic stem cell transplantation between December 1998 and September 1999, at the Yonsei University College of Medicine, Severance Hospital. 10 donors were evaluated for control. Blood samples of the recipients were taken at day 14 before allogeneic stem cell transplantation and +10, +17, +24 after allogeneic stem cell transplantation. Blood samples of the donors were taken at day 2 before allogeneic stem cell transplantation. All staining was performed with monoclonal antibodies and OX-40, CD4, CD8 expression on lymphocytes was analyzed by flow cytometry. Mixed chimerism was determined by using the variable number of tandem repeats (VNTR) by polymerase chain reaction (PCR) in one patient. Results:OX-40 expression on CD4+ T lymphocytes of healthy donors and recipients before stem cell transplantation was with a mean percentage of 8.1±4.6%(1.7~16.9%), 15.5±7.8% (2.4~27.2%). OX-40 expression by CD8+ T lymphocytes of healthy donors and stem cell transplantation recipients was undetectable. The expression of OX-40 as a percentage of the CD4+ cells of recipients after stem cell transplantation was increased at day +10, day +17, day +24 compared with at day -14 (p=0.01, 0.02, 0.01, respectively). Six out of sixteen patients developed GVHD. OX-40 expression on CD4+ T lymphocytes of the patients with GVHD was 33.9±6.8%. But no difference in the kinetics of OX-40 expression by CD4+ T cells was observed between the patients that did or did not develop GVHD, nor did the clinical effect of any treatment given for GVHD correlate with alterations in OX-40 expression by CD4+ T cells. After stem cell transplantation, one patient showed mixed chimerism in peripheral blood cells by VNTR-PCR in one patient analyzed. Conclusion: Our observation do not support the view that OX-40 expression is predictive of GVHD or is a useful tool for monitoring response to GVHD. In addition, earlier suggestions to develop a therapeutic approach aimed at the elimination of CD 4+ OX-40+ lymphocytes are not supported by our findings.

동종 골수이식후 재발한 급성 골수성 백혈병에서 구제화학요법후 동종 말초혈액조혈모세포 이식 1례

이석,정소영,김성철,서형찬,유내춘,민유홍,한지숙,고윤웅 대한조혈모세포이식학회 1996 대한조혈모세포이식학회지 Vol.1 No.1

Patients who relapse early after allogeneic bone marrow transplantation(BMT) for acute leukemia have little prospect of prolonged survival, as salvage chemotherapy or second transplants are rarely effective. An alternative therapeutic strategy is to provoke a graft-versus-leukemia(GVL) effect by the infusion of PBSC(peripheral blood stem cells) or leukocytes from the original bone marrow donor without attempts at graft-versus-host disease(GVHD) prophylaxis. This approach has been used with some success in patients with chronic myelogenous leukemia to treat relapse after transplant by an adoptive immunotherapy. The role of this approach in patients with acute myelogenous leukemia(AML) has still to be defined. We report a successful case of salvage chemotherapy followed by donor PBSC infusion for the treatment of relapse after allogeneic BMT in AML. The patient was a 16-year-old female with AML-M4 in relapse after allogeneic BMT on day +87. We planned to achieve complete remission(CR) with the two cycles of salvage chemotherapy followed by the infusion of donor PBSC mobilized by granulocyte colony-stimulating factor(G-CSF) at a dose of 10μg/kg/day subcutaneously for 5 days without GVHD prophylaxis. By one leukapheresis, the total mononuclear cells were 10.0×108/kg; the CD34 positive cells were 26.0×106/kg; the CFU-GM were 15.5×105/kg of recipient weight.. No T lymphocyte depletion was carried out on the peripheral blood cells collected and the total T lymphocytes were 7.5×108/kg. The time interval between relapse after allogeneic BMT and PBSC infusion was 63 days. After transplant, the neutrophil count exceeded 0.5×103/㎕ on day 10and the platelet count exceeded 20.0×103/㎕ on day 14. The patient developed skin rashes consistent with clinical grade 1 acute GVHD requiring immunosuppressive therapy on day 10. CR was confirmed with tri-lineage engraftment in bone marrow samples on day 20, and the patient is still in CR without any evidence of GVHD at present(day +150).

우측 쇄골하 동맥과 흉벽을 침범한 침습성 Aspergillosis 1 예

이석,최병현,민유홍,김성철,한지숙,윤용석,서형찬,고윤웅,유내춘,정소영 대한내과학회 1997 대한내과학회지 Vol.53 No.2

Invasive aspergillosis is an infection that occurs in immunocompromised patients. Its prevalence was increased in the last decade with progression of antineoplastic chemotherapy and immunosuppressive therapy after transplantation. Because it carries a high mortality and morbidity, early diagnosis and aggressive treatment are critical for successful management. In many patients, invasive aspergillosis remains confined to the lung although direct extension to pleural cavity or pericardium has been reported. However great vessel involvement is rare. Therefore we report a case of invasive aspergillosis involving right subclavian artery and chest wall in a patient after chemotherapy for acute lympoblastic leukemia.

급성 전골수성 백혈병에 동반된 Wernicke disease 1 예

이석,민유홍,김현수,한지숙,이상학,유내춘,서형찬,고윤웅,정소영 대한내과학회 1998 대한내과학회지 Vol.54 No.1

Wernicke's disease is a condition produced by thiamine deficiency; more than 90% of the cases are observed in chronic alcoholics. Other less frequent conditions associated with Wernicke disease are gastric disorders, prolonged parenteral nutrition, uremia, hemodialysis, hyperemesis gravidarum, prolonged starvation, and AIDS. We report a 41-year-old female patient of Wernicke disease associated with nausea and prolonged parenteral nutrition after chemotherapy of acute promyelocytic leukemia. She has got thiamine replacement therapy and most symptoms were improved. She was discharged after complete remission of leukemia and recovery of normal diet.

철결핍성 빈혈환자의 내원시 검사 소견

강한걸,신석균,최소연,김현수,송영구,서형찬,김효철 아주대학교 1996 아주의학 Vol.1 No.2

저자들은 철결핍성 빈혈 환자들의 내원시 검사소견을 관찰하여 이들의 특성 및 진단에 유용한 지표를 찾고 아울러 혈청 내 철의 정도를 반영할 수 있는 적혈구지수가 있는 지 알아보고자 1994년 1월부터 1996년 1월까지 아주대학교 부속대학병원 혈액종양내과에 내원하여 Coulter STK A2를 통해서 얻은 적혈구지수와 혈청 철, 혈청 총철결합능력, 혈청 ferritin을 측정하여 진단된 IDA환자 130례를 대상으로 다음과 같은 결과를 얻었다. 1) 전체 환자의 평균연령은 36.3±11.6세였으며 12세에서 65세까지의 연령분포를 보였다. 2) 전체 환자의 혈색소는 8.0±2.0 g/㎗이었고, 헤마토크리트 26.0±5.4%, MCV 68.8±11.3 fl, MCH 21.8±4.6 pg, RDW 18.5±4.0%, 혈청 철 25.0±15.1 ㎍/㎗, 혈청 총철결합능력 422.0±62.7 ㎍/㎗, ferritin 6.7±2.3 ㎍/㎗이었다. 3) 환자들이 호소하는 증상들은 월경과다가 36.9%, 현기증이 34.6%, 만성두통 32.3%, 만성피로 17.7% 그리고 소화기계 장애가 16.9%를 나타내었다. 4) 빈혈의 주요 원인으로서는 월경과다가 75례(57.7%), 위십이지장 궤양이 18례(13.8%), 사춘기/임신으로 인한 철의 요구량 증가가 19례(14.6%)였으며 치질로 인한 출혈이 11례(8.5%)이었고 원인불명이 17례였다. 5) 대상환자들을 혈색소치 9.0 g/㎗를 기준으로 하여 두 그룹으로 분류하였으며 혈색소가 9 g/㎗이상인 경한 빈혈 그룹에서 혈색소와 MCV는 유의한 상관관계(r=0.6584, p<0.05)가 있었으며, 혈색소가 9 g/㎗ 미만인 중한 빈혈 그룹에서 혈색소와 MCHC가 유의한 상관관계(r=0.4305, p<0.05)를 나타내여 경한 빈혈에서는 MCV가 중한 빈혈에서는 MCHC가 의미가 있음을 시사하고 있다. 5) RDW와 MCV는 두 그룹 모두에서 반비례 관계를 보였지만, 빈혈이 경한 그룹에서는 통계적으로 유의한 상관관계(r=-0.2985, p<0.05)를 보였고, 빈혈이 중한 환자그룹에서는 통계적으로 상관관계(r=-0.1208, p<0.05)가 유의하지 않아서, IDA 초기에는 MCV와 RDW가 의미가 있겠지만 중한 빈혈인 경우에는 의미가 없음을 보여 주었다. 6) 새로운 지표 MCV/RDW 비값이 fe/TIBC 포화도와 상당히 유의한 양의 상관관계(r=0.4763, p<0.005)가 있었고 5.1 이하인 경우에는 85.4%의 민감도로 IDA를 진단할 수 있겠다. 이상의 결과에서 혈청 철의 생화학적 지표에 앞서 단순한 일반 혈액검사에서 MCV/RDW를 계산함으로써 IDA의 선별검사로 사용할 수 있으며 5.1 이하의 범위에서 IDA를 진단을 한다면 85.4%의 민감도로 예측할 수 있다. To evaluate the laboratory findings in patients with iron deficiency anemia(IDA) at initial presentation and to define useful screening tests such as RBC indices and markers of serum iron, we studied 130 patients with the diagnosis of IDA who visited Ajou University Hospital from July 1994 to January 1996. The results of the study are as follows; 1) The mean age of IDA patients were 36.3 ±11.6 years old and ranged from 12 to 65 years old. 2) The mean laboratory values at initial visits were hemoglobin 8.3±2.0 g/dl, hemalocrit 26.0±5.4%, mean corpuscular volume 68.8±11.3 fl, mean corpuscular hemoglobin 21.8±4.6 pg, RDW 18.5±4.0%, serum iron 25.0±15.1 ㎍/dl, TIBC 422.0±62.7 ㎍/dl and serum feiritin 6.7±2.3 ㎍/dl. 3) Frequent symptoms and signs were menorrhagia(36.9%), dizziness(34.6%), headache(32.3%), easy fatigability(17.7%) and G-Ⅰ trouble(16.9%). 4) Frequent causes of IDA were menorrhagia in 75(57.7%) cases, gastrointestinal ulcer in 18(13.8%) cases, increased demand for iron due to pregnancy and growth spun in 19(14.6%) cases, hemorrhoidal bleeding in 11(8.5%) cases. 5) When patients were divided into two groups(Hb≥9 g/dl as mild, Hb<9 g/dl as severe anemia), the group with Hba.9 g/dl showed a significant correlation between hemoglobin and MCV(r=0.6584, p<0.05). However, in the group with Hb<9 g/dl, there was a significant correlation between hemoglobin and MCHC(r=0.4305, p<0.05). 5) Negative correlation was observed between MCV and RDW in both groups, <although statistically significant in the mild group(r=-0.2985, p<0.05) but not significant in the severe group(r=-0.1208, p>0.05)> indicating more microcytic in RBC index and anisocytosis in RBC shape. 6) MCV/RDW ratio was correlated significantly with Fe/TIBC saiuration(r=0.4763, p<0.005) and MCV/RDW ratio of less than 5.1. This is lo be the most sensitive index in the diagnosis of IDA, sensitivity 85.4% in both mild and severe groups. In conclusion, in addition to serum iron markers, MCV, MCHC and RDW have been used as screening tests and prediction for IDA. We suggest that the ratio of MCV/RDW(fl/%) less than 5.1 is one of the most sensitive index in screening and diagnosing IDA with 85.4% sensitivity rate.

크론씨병에 동반된 골수이형성증후군 2례

김현진,김진석,김동기,이승태,정준원,장준호,서형찬,민유홍,한지숙,고윤웅,김원호 대한혈액학회 2002 Blood Research Vol.37 No.1

원발성 알도스테론증을 보인 거대부신선종 1예

신동환,홍순원,이지현,허갑범,이현철,임승길,송영득,남문석,차봉수,박정수,박재민,서형찬,최영화 대한내분비학회 1996 Endocrinology and metabolism Vol.11 No.3

Primary aldosteronism is a syndrome chracterized by hypokalemic alkalosis and hypertension. Small sized adrenal cortical adenomas have been the major cause of this syndrome in most of the patients. However, if the adrenal mass is larger than 6cm in diameter and with irregular consistency, malignancy is more favored. We experienced a patient who had a giant adrenal adenoma with primary aldosteronism. A 24-year-old female presented with hypertension, hypokalemia, low plasma renin, and high plasrna aldosterone levels, was found to have a 6×5.5×5 cm sized left adrenal tumor by MRI. Her clinical laboratory feature did not revealed any evidence of Cushing's syndrome or pheochromocytoma. Preoperatively adrenal carcinoma presenting pure adrenal aldosteronism was suspected due to large size and heterogenous signal character of the adrenal mass in radiologic study. At operation well encapsulated, round giant adrenal tumor weighing 65gm(4.5×4×4 cm) was removed. There was no evidence of metastasis with return of adrefunction to normal after surgery. Benign adrenal adenoma was confirmed by the gross morphology and the histologic features(J Kor Soc Endocrinol 11:348-354, 1996).