급성 백혈병 환자에서 감염증의 양상 및 예후인자에 관한 연구 : 1988년∼1995년까지

정희진,김병수,신상원,김열홍,김우주,김민자,김준석,박승철,김권범 대한감염학회 1998 감염 Vol.30 No.3

목적 : 급성 백혈병의 경우 골수기능이 억제되고 항암화학요법에 따른 골수기능 저하로 감염의 위험이 증가하며 감염의 치료가 환자의 생존에 큰 영향을 미치게 된다. 이에 저자들은 1988년부터 1995년까지 고대 구로병원에 급성 백혈병으로 입원했던 환자들 중 입원 기간 내 감염이 있었던 경우를 대상으로 하여 감염의 위험인자 및 감염증의 예후를 후향적으로 분석함으로써 향후 급성 백혈병환자의 감염의 치료에 대한 지침을 얻고자 하였다. 방법 : 급성 백혈병으로 확진된 환자들 중 감염병에 이환된 경우를 대상으로 하여 각각을 미생물학적 확인감염, 임상적 확인감염, 그리고 설명 불가열로 구분하였다. 각각의 경우에서 감염 당시의 호중구 수, 호중구 감소 기간, 항암화학요법과의 연관성, 감염 병소, 배양된 검체 및 원인균, 선택적 소화관 살균법의 사용여부 및 골수회복 여부 등을 조사한 후 환자의 예후와 어떤 관계가 있는 지 조사하였다. 결과 : 연구 대상은 총 113예로 남녀비는 46:67 이었고 평균연령은 34±13세, 진단은 급성 골수성 백혈병 (AML)이 84예, 급성 림프구성 백혈병(ALL)이 29예였으며, 감염시 평균 호중구수는 663±1678/㎣이었고, 호중구 감소 기간은 평균 18±13일이었다. 감염양상은 항암화학요법과 연관된 감염이 84예로 대부분이었고 미생물학적 확인 감염이 40예로서 35%였으며, 폐렴과 원발성 패혈증이 각각 20예와 19예로 가장 많았고, 카테터 연관 감염이 7예로 나타났다. 배양된 균주는 E. coli가 10예(25%)로서 가장 많았으며, 전체적으로 E. coli, P. aeruginosa, K. pneumoniae 등의 그람음성균이 63%로 대부분을 차지하였으나 최근 그람양성구군 및 진균의 분리율이 증가하는 양상을 보였다. 감염증의 예후를 분석한 결과 진균 감염인 경우나 호중구 감소 기간이 긴 경우 사망률이 높았으며 그 중에서도 골수 기능이 회복 여부가 환자들의 생존과 통계적으로 유의한 연관이 있었다.(P=0.01). 결론 : 급성 백혈병 환자들에서의 감염은 관해유도화학요법 후 초래되는 호중구 감소와 유의한 관계가 있으며, 폐렴 및 패혈증의 임상양상을 보이는 경우가 흔하고, 원인균별로는 그람 음성균이 주류를 이루나 최근 그람 양성균 감염이 증가하는 추세를 보였다. 감염의 예후 인자로는 진균 감염인 경우나 호중구 감소 기간이 긴 경우 사망률이 높았으나 골수 기능의 회복여부가 결정적인 역할을 하는 것으로 나타나, 향후 급성 백혈병 환자의 치료에 있어 감염 빈도의 감소와 감염에서의 조속한 회복을 위해서는 골수 기능의 회복에 중점을 두어야 할 것으로 사료된다. Background : Infection is one of the most important and fatal complications in patients with acute leukemia. The characteristics of infection in acute leukemic patients are different from those in other diseases by the lack of normal inflammatory responses or distinct clinical evidence except fever. To improve the outcome of acute leukemia, it is very important to recognize the risk factors, patterns and prognostic factors of acute leukemia. Methods : We analyzed retrospectively the patterns of infection from 113 febrile patients with acute leukemia from January, 1988 to December, 1995. To determine the prognostic factors and the outcome of infection, the following variables were analyzed: the presence of neutropenia, use of chemotherapeutic agents, type and site of infections, isolated organisms, gastrointestinal decontamination, duration of neutropenia, and bone marrow recovery. Results : Out of 113 febrile patients with acute leukemia, 84 infection episodes(74%) occurred after chemotherapy. The mean duration of neutropenia was 18±13 days. The incidence of microbiologically-documented infection(MDI) was 35%(40/113). Pneumonia was the most common infection(26%), followed by primary sepsis(24%), catheter-related infection(9%). In cases of MDI, 63% were caused by gram-negative bacteria, followed by gram-positive bacteria(28%), and fungi(10%). Escherichia coli(25%) was the most common isolated in MDI. Regarding the prognostic factors in cases with infections, the recovery of bone marrow function was the only statistically significant factor(P=0.01). Conclusion : Infection has been a major cause of morbidity and mortality in acute in acute leukemic patients. To prevent infection and thereby improve the prognosis of acute leukemia, restoration of bone marrow function at early stage is important.

S-485 : Chemotherapy in population including elderly patients with recurrent or advanced soft tissue sarcoma

( Hong Jun Kim ),( In Keun Choi ),( Se Ryeon Lee ),( Seung Tae Kim ),( Hwa Jung Sung ),( Kyong Hwa Park,),( Sang Cheul Oh ),( Jae Hong Seo ),( Sang Won Shin ),( Yeul Hong Kim ),( Jun Suk Kim ) 대한내과학회 2013 대한내과학회 추계학술대회 Vol.2013 No.1

Introduction: Recent study reported that 38 percent of new patients with soft tissue sarcoma were aged more than 65 years. However, few studies reported clinical outcomes after chemotherapy in elderly patients with recurrent or advanced soft tissue sarcoma. Elderly patients hesitate to receive chemotherapy. But, an equal response to chemotherapy is expected in elderly patients as in young patients. Hence, we aimed to study the clinical results of chemotherapy in elderly patients with recurrent or advanced soft tissue sarcoma. Patients and Methods: 97 patients were admitted for chemotherapy at the Korea University Anam, Guro, and Ansan Hospital s between 2003.3 and 2012.4. Patients were treated with an appropriate chemotherapy regimen. Results: The median age of the patients in the entire group was 52 years. Patients received a median of 4 cycles of chemotherapy. The median overall survival for the entire group was 61 months (95% CI: 29.3-92.7 months). 33 patients were identified as elderly patients aged 60 years or older. In the elderly group, the most common type of soft tissue sarcoma was leiomyosarcoma (21.2%). The median number of chemotherapy cycles was three and median survival was 15 months in the elderly group. In the elderly group, one patient had a complete response. There were four partial responses. 14 patients had progressive disease. In the subgroup analysis, 51 of 64 patients (79.75%) in the non-elderly group were responders, while 19 of 33 patients (57.6%) in elderly group responders were responders (Chi-square test p=0.03). However, there was no statistically significant difference in survival between the elderly and non-elderly groups (p=0.11, log-rank test). Disease burden and response to chemotherapy were predictive of survival in elderly patients with recurrent or advanced soft tissue sarcoma. Conclusions: Taking only an age-based decision for systemic chemotherapy seems not to be reasonable in elderly patients with recurrent or advanced soft tissue sarcoma. A judicious decision needs to be taken for selecting the candidate for chemotherapy in elderly patients with recurrent or advanced soft tissue sarcoma after considering the benefit and toxicity of chemotherapy.

진행성 위암환자에 대한 Epirubicin , Cisplatin , 경구 UFT 및 Leucovorin 복합항암화학요법의 효과

김열홍(Yeul Hong Kim),전훈재(Hoon Jai Chun),현진해(Jin Hai Hyun),윤소영(So Young Yoon),서재홍(Jae Hong Seo),최철원(Chul Won Choi),김병수(Byung Soo Kim),목영재(Young Jae Mok),김종석(Chong Suk Kim),김준석(Jun Suk Kim) 대한내과학회 1999 대한내과학회지 Vol.56 No.6

N/A Objective : UFT plus leucovorin treatment had favorable activity and tolerable toxicity in patients with advanced stomach cancer. Recently, high response rates have been reported in patients with advanced stomach cancer with a schedule of epirubicin, cisplatin, and protracted infusion of 5-fluorouracil (5-FU). The advantage of long term oral administration of UFT is that this treatment might be used to mimic protracted infusions of 5-FU. Instead of inconvenience of infusion pump and intravenous catheter for protracted infusion of 5-FU, we administered UFT plus leucovorin in this treatment. Methods : Thirty-seven patients with locally advanced or metastatic stomach cancer received epirubicin, cisplatin, oral UFT plus leucovorin. Epirubicin 50 mg/m2 and cisplatin 60 mg/m2 were administered on day 1 by intravenous injection. UFT 360 mg/m2/day in conjunction with leucovorin administered at 25 mg/m2/day per os in divided daily doses for 21 days followed by a 7-day rest period. Courses were repeated every 4 weeks. The median age of the patients was 55 years with a median World Health Organization (WHO) performance status of 1. Patients received a median of four courses of treatment (range, 2 to 10). Results : Among 37 evaluable patients, two patients achieved complete response, and eighteen had partial responses, for an overall response rate of 54% (95% confidence interval; 39% to 70%). Stable disease was reported in 12 patients (32.5%) and another 5 (13.5%) showed disease progression. The median duration of survival was 10 months (range, 2 to 15+). The main toxicity was nausea/vomiting, leukopenia, diarrhea and oral mucositis. Significant toxicity (WHO grade 3 or 4) included leukopenia in fourteen patients (39.8%), nausea/ vomiting in eleven (29.7%), oral mucositis in five (13.5%), and diarrhea in four (10.8%) patients. Conclusion : We conclude that epirubicin, cisplatin, oral UFT plus leucovorin, a convenient out-patient regimen, has a significant activity in patients with stomach cancer and has tolerable toxicities.

Oral Etoposide, Ifosfamide and Cisplatin in the Treatment of Extensive Disease Small Cell Lung Cancer

Seok Jin Kim,HwaJ ung Sung,Kyong Hwa Park,So Young Yoon,Sang Cheul Oh,Jae Hong Seo,Chul Won Choi,Byung Soo Kim,Sang Won Shin,Yeul Hong Kim,Kwang Taek Kim,Young Ho Choi,Jun Suk Kim 대한암학회 2002 Cancer Research and Treatment Vol.34 No.6

Follow-up Study of Peripheral Blood Carcinoembryonic Antigen mRNA Using Reverse Transcription–Polymerase Chain Reaction as an Early Marker of Clinical Recurrence in Patients With Curatively Resected Gastric Cancer

Seo, Jae Hong,Choi, Chul Won,Kim, Byung Soo,Shin, Sang Won,Kim, Yeul Hong,Kim, Jae Sun,Lee, Sang Woo,Choi, Jae Hyun,Park, Yung Tae,Mok, Young Jae,Kim, Chong Suk,Kim, Jun Suk Lippincott Williams Wilkins, Inc. 2005 American journal of clinical oncology: cancer clin Vol.28 No.1

In this study, we evaluated the clinical significance of detecting carcinoembryonic antigen (CEA) mRNA in the peripheral blood samples of patients with gastric cancer. We analyzed the peripheral blood of 46 patients with gastric cancer who had undergone curative resection. The presence of CEA mRNA was serially monitored using a CEA-specific reverse transcription–polymerase chain reaction (RT-PCR) every 2 months. The clinical recurrence rates according to category were as follows: 100% (3 of 3) in the positive conversion, 0% (0 of 18) in the negative conversion, 50% (3 of 6) in the always-positive, and 10.5% (2 of 19) in the always-negative category. The recurrence rate was 66.7% (6 of 9) in the positive group and 5.4% (2 of 37) in the negative group (P ≤0.00022). Multiple logistic regression analysis demonstrated that only group variable had a significant effect on clinical recurrence (P = 0.015). We conclude that RT-PCR analysis of CEA mRNA in the peripheral blood seems to be a promising tool for the early detection of micrometastatic circulating tumor cells in gastric carcinoma patients and that it can be useful used to identify patients at risk for recurring.

Phase I dose escalation study of docetaxel with a fixed dose of S-1 in combination chemotherapy for advanced gastric cancer

Kim, Yeul Hong,Seo, Hee Yeon,Jeen, Yoon Tae,Kim, Hoon-Kyo,Shim, Byoung Yong,Yang, Jinmo Springer-Verlag 2009 Cancer chemotherapy and pharmacology Vol.63 No.2

동종 골수이식에 거부반응을 보인 재생불량성 빈혈에서 G-CSF로 가동화된 동종 말초혈액 조혈모세포이식을 통하여 완전생착을 보인 1례

김병수,최인근,김석진,서재홍,신상원,김열홍,김준석 대한조혈모세포이식학회 1997 대한조혈모세포이식학회지 Vol.2 No.1

Rejection after allogeneic BMT is one of the major complications of aplastic anemia with a high risk of mortality. We describe a patient who experienced rejection after allogeneic BMT entered a durable remission subsequent to treatment with ALG(10 mg/kg/day for 5 days) and donor peripheral blood stem cell transplantation mobilized with G-CSF(mononuclear cell: 6.5×10^(8)/kg, CD34^(+) cell: 5.4×10^(6) kg). Therapy was well tolerated. G-CSF infusion after allogeneic PBSCT was not done. Neurophil recovery to 1,000/μL and platelet engraftment to 50,000/μL were achieved at 8 and 15 days following the first dose of allogeneic PBSCT, respectively. The patient is currently well with a stable engraftment 10 months following allogeneic PBSCT.

재발한 전이성 유방암 환자에서의 고용량 Paclitaxel 화학요법 및 CD34+ 조혈모세포이식

김병수,서재홍,최철원,신상원,김열홍,김준석 대한조혈모세포이식학회 2000 대한조혈모세포이식학회지 Vol.5 No.2

배경:저자 등은 고려대 의료원에서 유방암의 수술 및 anthracycline을 포함한 화학요법 후 재발한 불량한 예후인자를 지닌 전이성 유방암 환자들에게 시행한 고용량 paclitaxel 화학요법 후 Immune-magnetic 법으로 채집된 자가 CD34+ 조혈모세포이식의 경험을 보고하고자 한다. 방법:수술 및 CAF (cyclophosphamide, adriamycin, 5-FU) 화학요법 후 관해를 유지하다가 전이성으로 재발한 32~59세(중앙값: 40세)의 유방암 환자 8명을 대상으로 하였다. 화학요법 후 재발 발견까지의 기간은 7~46개월이었다. 우선 paclitaxel (175 mg/m2) 및 ifosfamide (1,800 mg/m2) 요법을 4회 실시하였고, 모두에서 부분 반응 이상의 효과가 관찰되었다. CD34+ 조혈모세포는 수술실에서 채집된 골수혈로부터 CEPRATEⓡ System을 이용하여 분리한 다음, controlled-rate freezing 후 -196℃ 액체질소에 보존되었다가 paclitaxel (625 mg/m2), cisplatin (165 mg/ m2), cyclophosphamide (5,625 mg/m2)으로 이루어진 고용량 화학요법 후 다시 환자에게 이식되었다. 본 시술의 평가를 위하여 CEPRATEⓡ System의 CD34+ 조혈모세포 분리효율(%) 및 조혈기능 회복까지의 기간, 그리고 이식 후 합병증을 포함한 현시점까지의 경과를 분석하였다. 결과:각 환자 당 CD34+ 조혈모세포의 분리효율의 분포는 53~90%로 그 중앙값은 74%이었다 이식 후 화학요법과 관련된 부작용으로는 오심 및 구토, 점막염, 중추 및 말초 신경계 증상들이 전례에서 관찰되었고, 한 환자에서는 흡인성 폐렴으로 사망하였다. 그리고, 이식 후 7명의 환자들에서 저과립구성 발열이 발생하였으며, 그 기간의 중앙값은 4일(범위; 2~7일)이었다. 이식 후 과립구 수가 500/μL 및 2,000/μL 이상으로 회복되는 데 걸리는 기간의 중앙값은 각각 11일(범위; 9~17일), 23일(범위; 15~38일)이었고 혈소판 수가 20,000/μL 및 50,000/μL 이상으로 회복되는데 소요된 기간의 중앙값은 각각 15일(범위; 12~23일), 18일(범위; 14~35일)이었다 흡인성 폐렴으로 사망한 1명을 제외한 7명에서의 추적기간의 중앙값은 7 개월(범위; 3~35개월)이었다. 이 중 이식시 완전관해였던 환자가 3명, 부분관해였던 환자가 4명이었고, 부분관해 환자들 중 1명에서는 이식 후 완전관해로 호전이 되었다. 그러나 본 환자들 모두에서 이식 후 2-36+ 개월에 재발 혹은 진행 소견을 보이면서 이식 후 3-37+ 개월에 사망하였다. 결론:본 연구를 통하여 anthracycline을 포함한 기존의 항암제 치료 후 재발한 불량한 예후인자들을 지닌 환자들을 대상으로 한 고용량 paclitaxel 화학요법 후 CD34+ 조혈모세포이식은 기존의 고용량 화학요법 후 자가 조혈모세포이식의 성적과 차이가 없었음을 알 수 있었지만, 비교적 안전하게 우리나라의 환자들에서도 적용될 수 있다는 사실을 본 연구를 통하여 확인할 수 있었다. 그러므로, 본 연구를 기초로 하여 고용량 화학요법으로 치료효과를 극대화시킬 수 있는 예후인자들을 지닌 재발성 전이성 유방암 환자들을 대상으로 한 추가 연구가 필요하리라고 사료된다. Background: Autologous hematopoietic stem cell transplantation using a positive purging method to detect CD34+ cells has a benefit of having a less chance of contamination with cancer cells in the transplanted blood containing stem cells than that using a negative purging method. And, paclitaxel is approved to be a new effective chemotherapeutic agent for breast cancer. So, the clinical results of the CD34+ hematopoietic stem cell transplantation with high-dose paclitaxel chemotherapy in the recurred metastatic breast carcinoma patients have been reported in this study. Methods: 8 patients (woman, median age: 40 years, range; 32~59 years) with metastatic (liver, bone, lymph nodes) breast carcinoma recurred after the treatment of curative operation and adjuvant CAF (cyclophosphamide, adriamycin, 5-FU) chemotherapy, have been enrolled in this study. All patients had been responded to 4 cycles of paclitaxel (175 mg/m2) and ifosfamide (1,800 mg/m2) chemotherapy. CD34+ hematopoietic stem cells were purified from bone marrow blood by CEPRATEⓡ SC Stem Cell Concentration System using avidin-coated polyacrylamide beads column. The high-dose chemotherapy regimen was consisted with paclitaxel (625 mg/m2), cisplatin (165 mg/m2), and cyclophosphamide (5,625 mg/m2). The separation yield of CD34+ hematopietic stem cells, the hematopoietic recovery time, and the clinical outcomes of transplantation have been evaluated in this study. Results: The separation yield of CD34+ hematopietic stem cells with CEPRATEⓡ SC Stem Cell Concentration System was ranged from 53~90% (median: 74%). All patients had been experienced nausea with vomiting, mucositis, central or peripheral neuropathy after high-dose paclitaxel chemotherapy. One patient had been expired due to aspiration pneumonitis. Neutropenic fever was developed in seven patients with the duration of 2~7 (median: 4) days. The median (range) duration of neutrophil recovery to 500/μL and 2,000/μL was 11 (9~17) and 23 (15~38) days, respectively. The median (range) duration of platelet recovery to 20,000/μL and 50,000/μL was 15 (12~23) and 18 (14~35) days, respectively. The median follow-up duration after transplantation was 7 (3~37) months. All patients experienced disease relapse or progression after 2-36+ months after transplantation. Therefore, overall rate of 3 year disease free survival in this study was 14.3 (1/7)%. Conclusion:CD34+ hematopoietic stem cell transplantation with high-dose paclitaxel chemotherapy in the recurred metastatic breast carcinoma patients seems to have no superior clinical outcome compared to the other modalities of high-dose chemotherapy with hematopoietic stem cell transplantation. But, we can find that high-dose paclitaxel (625 mg/m2, dose ratio; 3.57) therapy is relatively safe in Korean patients. Therefore, further studies targeted to the recurred metastatic breast cancer patients with moderate to good prognostic factors will be warranted.

The Effect of Metformin Treatment on CRBP-I Level and Cancer Development in the Liver of HBx Transgenic Mice

Kim, Jo-Heon,Alam, Morshedul,Park, Doek Bae,Cho, Moonjae,Lee, Seung-Hong,Jeon, You-Jin,Yu, Dae-Yeul,Kim, Tae Du,Kim, Ha Young,Cho, Chung Gu,Lee, Dae Ho The Korean Society of Pharmacology 2013 The Korean Journal of Physiology & Pharmacology Vol.17 No.5

Retinoids regulate not only various cell functions including proliferation and differentiation but also glucose and lipid metabolism. After we observed a marked up-regulation of cellular retinol-binding protein-I (CRBP-I) in the liver of hepatitis B virus x antigen (HBx)-transgenic (HBx Tg) mice which are prone to hepatocellular carcinoma (HCC) and fatty liver, we aimed to evaluate retinoid pathway, including genes for the retinoid physiology, CRBP-I protein expression, and retinoid levels, in the liver of HBx Tg mice. We also assessed the effect of chronic metformin treatment on HCC development in the mice. Many genes involved in hepatic retinoid physiology, including CRBP-I, were altered and the tissue levels of retinol and all-trans retinoic acid (ATRA) were elevated in the liver of HBx Tg mice compared to those of wild type (WT) control mice. CRBP-I protein expression in liver, but not in white adipose tissue, of HBx Tg mice was significantly elevated compared to WT control mice while CRBP-I protein expressions in the liver and WAT of high-fat fed obese and db/db mice were comparable to WT control mice. Chronic treatment of HBx Tg mice with metformin did not affect the incidence of HCC, but slightly increased hepatic CRBP-I level. In conclusion, hepatic CRBP-I level was markedly up-regulated in HCC-prone HBx Tg mice and neither hepatic CRBP-I nor the development of HCC was suppressed by metformin treatment.

Genome-Wide Association Study of Lung Cancer in Korean Non-Smoking Women

Kim, Jin Hee,Park, Kyunghee,Yim, Seon-Hee,Choi, Jin Eun,Sung, Jae Sook,Park, Ju-Yeon,Choi, Yi Young,Jeon, Hyo-Sung,Park, Jae Yong,Yoon, Hyoung Kyu,Kim, Yeul Hong,Yoo, Byung Su,Kim, Young Tae,Hu, Hae-J The Korean Academy of Medical Sciences 2013 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.28 No.6

<P>Lung cancer in never-smokers ranks as the seventh most common cause of cancer death worldwide, and the incidence of lung cancer in non-smoking Korean women appears to be steadily increasing. To identify the effect of genetic polymorphisms on lung cancer risk in non-smoking Korean women, we conducted a genome-wide association study of Korean female non-smokers with lung cancer. We analyzed 440,794 genotype data of 285 cases and 1,455 controls, and nineteen SNPs were associated with lung cancer development (<I>P</I> < 0.001). For external validation, nineteen SNPs were replicated in another sample set composed of 293 cases and 495 controls, and only rs10187911 on 2p16.3 was significantly associated with lung cancer development (dominant model, OR of TG or GG, 1.58, <I>P</I> = 0.025). We confirmed this SNP again in another replication set composed of 546 cases and 744 controls (recessive model, OR of GG, 1.32, <I>P</I> = 0.027). OR and <I>P</I> value in combined set were 1.37 and < 0.001 in additive model, 1.51 and < 0.001 in dominant model, and 1.54 and < 0.001 in recessive model. The effect of this SNP was found to be consistent only in adenocarcinoma patients (1.36 and < 0.001 in additive model, 1.49 and < 0.001 in dominant model, and 1.54 and < 0.001 in recessive model). Furthermore, after imputation with HapMap data, we found regional significance near rs10187911, and five SNPs showed <I>P</I> value less than that of rs10187911 (rs12478012, rs4377361, rs13005521, rs12475464, and rs7564130). Therefore, we concluded that a region on chromosome 2 is significantly associated with lung cancer risk in Korean non-smoking women.</P>