All - trans Retinoic Acid 가 급성전골수성백혈병의 관해유도와 혈액응고장애에 미치는 효과

김성권(Sung Gwon Kim),한치화(Chi Wha Han),김유진(Yoo Jin Kim),김동욱(Dong Wook Kim),진종률(Jong Youl Jin),민우성(Woo Sung Min),박종원(Chong Won Park),김춘추(Choon Choo Kim),김동집(Dong Jip Kim) 대한내과학회 1997 대한내과학회지 Vol.53 No.2

N/A Objectives: APL, which characteristically shows t(15:17), accompanies fatal coagulopathy during remission induction with systemic chemotherapy alone. ATRA, a derivative of vitamin A, can differentiate APL cells as well as HL-60 cells in vitro and induce higher rate of complete remission(CR). Hence, we assessed the effect of ATRA on remission induction and coagulopathy in APL patients. Methods: (1) 42 patients diagnosed histologically in St. mary's hospital from June 1991 to June 1994 were included. (2) We compared the CR rate, the time required for restoration of derranged coagulation profiles, and the amount of coagulation factors including platelets among the chemotherapy group (control) and ATRA group. Results: 1) There was no difference in CR rate between the control group and ATRA group [84.2%(16 out of 19) vs 87.0%(20 out of 23), p>0.05)] and also no difference between two subgroups of ATRA [ATRA with chemotherapy; 83.3%(10 out of 12) vs ATRA without chemotherapy; 90.9%(10 out of 11), p>0.05] 2) In the ATRA group, the CR rate of newly diagnosed patients was 82.4%(14 out of 17). The first relapsed patients (4) and the second (2) were all achieved CR. 3) The mean duration of coagulopathy, time to normalization of PT, aPTT, FDP, fibrinogen level, was 12.0±10.4, 11.1±10.2, 16.5±9.3, 15.4±10.2 days after chemotherapy alone and 4.5±4.4, 3.7±3.7, 8.9±6.1, 8.1±6.5 days in the ATRA group(p<0.05). The amount of fresh frozen plasma used in the ATRA group for the purpose of correction of coagulopathy were significantly lower than the control group(p<0.05). The incidence of profound coagulopathy during the remission induction treatment in the ATRA group was significantly lower than the control group[40% (8 out of 20) vs 96.7%(13 out of 15), p<D.05]. And the amount of platelet transfusion was not different between two groups. 4) During the treatment with ATRA, four patients showed leukocytosis, but no patient developed typical retinoic acid syndrome. Other toxicities attributable to ATRA were headache in one case, increase in transaminase in one case, bone pain in one case. These side effects were mostly short-term and easily controlled by appropriate symptomatic therapy. Conclusion: (1) ATRA is relatively safe drug for inducing CR in patients with APL who are diagnosed freshly and even in relapse. (2) Also it is effective for reducing the severity of coagulopathy associated with APL itself.

증례 : 혈액종양 ; 50대 남자 환자에서 대세포 폐암으로 오인된 원발성 종격동 융모막암 1예

김영신 ( Young Shin Kim ),한치화 ( Chi Wha Han ),정윤화 ( Yun Hwa Jung ),정민영 ( Min Young Jeong ),고성우 ( Seong Woo Go ),윤경진 ( Kyung Jin Yun ),정한희 ( Han Hee Chung ) 대한내과학회 2014 대한내과학회지 Vol.86 No.5

남자에서 발생된 성선 외 융모막암은 매운 드문 종양으로 종격동에서 발생하는 경우 폐암이나 호지킨 림프종으로 오인되기 쉽다. 특히 일반적인 나이를 비롯하여 전이 방식 등 생식세포암의 임상적 특징을 보이지 않는 경우와 경피적 침생검에서 분화도가 좋지 않은 상피암 형태로 관찰되는 경우 진단이 지연될 수 있다. 저자들은 50대의 남자에서 경피적 생검 결과 대세포 폐암이 의심되어 절제술을 시행한 후 원발성 종격동 융모막암으로 진단된 1예를 경험하였기에 교훈적인 증례로 보고하는 바이다. Primary mediastinal choriocarcinoma is an extremely rare extragonadal germ cell malignancy. A 58-year-old male presented with a lung mass, which was incidentally discovered during a periodic medical checkup. Percutaneous needle biopsy showed poorly differentiated carcinoma with large pleomorphic morphology. After the patient underwent right upper lobectomy and lymphadenectomy, the final diagnosis was choriocarcinoma. The patient received four sequential cycles of BEP chemotherapy (bleomycin, etoposide, cisplatin). After completion of BEP chemotherapy, follow-up positron emission tomography (PET) showed a complete metabolic response. Although the mediastinum is one of the most common primary sites of extragonadal germ cell tumors, primary mediastinal choriocarcinoma is liable to be misdiagnosed as lung cancer or Hodgkin lymphoma. Notably, large cell carcinoma of the lung can be confused with choriocarcinoma even after percutaneous needle biopsy. We report a case of primary mediastinal choriocarcinoma mimicking large cell carcinoma of the lung in a male patient in his 50s. (Korean J Med 2014;86:641-646)

증례 : 혈액종양 ; 림프종 환자에서 리툭시맙 치료 후에 발생한 저감마글로불린혈증 1예

노현진 ( Hyun Jin Noh ),공봉한 ( Bong Han Gong ),김영신 ( Young Sin Kim ),정윤화 ( Yun Hwa Jung ),우인숙 ( In Sook Woo ),한치화 ( Chi Wha Han ) 대한내과학회 2014 대한내과학회지 Vol.87 No.3

Rituximab, an anti-CD20 monoclonal antibody, is an effective target agent against the B lymphocytes in B-cell lymphoid malignancies and various lymphoproliferative diseases. Moreover, the toxicity of rituximab is less severe than that of conventional cytotoxic agents, which has promoted the widespread application of rituximab in the treatment of B-cell lymphoma. However, depletion of B lymphocytes by rituximab, which leads to secondary hypogammaglobulinemia, can cause deterioration of humoral immunity. Although immune reconstitution after hematopoietic stem cell transplantation is known to prevent prolonged hypogammaglobulinemia, very few cases of long-standing hypogammaglobulinemia have been reported. We report herein a case of prolonged hypogammaglobulinemia after rituximab-containing chemotherapy and splenectomy in a patient with non-Hodgkin`s lymphoma and discuss the clinical significance and pathogenetic mechanism of this phenomenon with a literature review. (Korean J Med 2014;87:357-362)

녹색 형광단백 유전자를 함유한 아데노바이러스 주입시 마우스 생체내 발현양상

진종률(Jong Youl Jin),송치원(Chi Won Song),김진아(Jea Na Kim),이희진(Hee Jin Lee),김태규(Tai Gyu Kim),한치화(Chi Wha Han),엄현석(Hyun Seok Eom),박수정(Soo Jeong Park),정대철(Dae Chul Jeong),정낙균(Nak Gyun Chung),김소연(Soh Yeon Kim) 대한내과학회 2001 대한내과학회지 Vol.61 No.5

N/A Background : The green fluorescent protein (GFP) from jelly fish, A equorea victoria, has become a versatile reporter for monitoring gene expression in a variety of cells and organisms . Using GFP as a marker protein we studied whether there are any differencies in the expression patterns among organs in mouse after intravenous injection of adenovirus vectors with GFP gene. Methods : Recombinant E1, E3- defective type 5 adenovirus vectors (2×10(8)/mouse) with CMV promoter and GFP gene were injected into mice via tail vein. On 3, 6, 9, 14, 21, 28 days after gene transfer, 5 mice per experiment s were sacrificed by cervical dislocation and obtained liver , lung, heart , kidney, spleen, small intestine and bone. Half of them were examined by optical microscope after H-E stain. Another half were examined by fluorescent microscope after frozen section. Western blotting were done for each samples with anti- GFP monoclonal antibody and obtained GFP bands were quantitatively compared using Gel-Doc (Bio- Rad, USA) image analyzer. Results : In all organs that we obtained, expression of GFPs are noticed 3 days after gene transfer and reached a maximum around 9th to 14th days, after then the intensities are slightly decreased but maintained until 28th days as determined by Western blotting. On fluorescent microscopic examination, GFPs are well and most frequently expressed on lung among all the examined organs. There are little expression of GFPs on liver parenchymal area around the sinusoids and central veins, although patchy expression of GFPs are observed along the liver capsules. GFPs are highly expressed around the splenic trabecula area but splenic pulp area, it is very spar sely expressed. GFPs are more frequently and highly expressed around the renal tubular area than gromerular area in kidneys. In small intestine, GFPs are expressed on mid portion of microvilli. GFPs are not expressed on myocardium except scanty expression on endocardium. Bone marrow showed GFPs but precise localization is difficult because bony spicules mashed bone marrow during the preparation of frozen section. No specific pathologic lesions possibly related with adenovirus administration are observed on microscopic examination of H-E stained specimens. Conclusions: GFPs can be detected in cells without the fixing and staining and a good marker to studying the kinetics and persistence of adenovirus mediated gene therapy. And there are different GFP expression patterns according to the organs after intravenous injection of adenovirus vectors with GFP gene in mouse.(Korean J Med 61:537- 545, 2001)

혈액종양 : 원발성 식도 미만성 거대 B세포 림프종 2예: 치료와 문헌적 고찰

김지혜 ( Ji Hye Kim ),정윤화 ( Yun Hwa Jung ),우인숙 ( In Sook Woo ),한치화 ( Chi Wha Han ),서민우 ( Min Woo Seo ),유상훈 ( Sang Hoon Yoo ),하소영 ( So Young Ha ) 대한내과학회 2015 대한내과학회지 Vol.88 No.2

Primary esophageal lymphoma is very rare, and most reported cases are histologically mucosa-associated lymphoid tissue lymphoma. Therefore, the principle treatment strategy for primary esophageal lymphoma focuses on local treatments, such as endoscopic mucosal resection or radiation therapy, but systemic chemotherapy plays the central role in the treatment of diffuse large B cell lymphoma (DLBCL). Generally, standard treatment for DLBCL is six or three cycles of R-CHOP chemotherapy followed by involved field radiation therapy according to stage. However, the optimal treatment strategy for primary esophageal DLBCL, and the role of additional radiation is not settled, due to a paucity of cases. Moreover, the clinical characteristics related to the etiology and natural course are also unknown. Here, we present two cases of primary esophageal DLBCL with a literature review. (Korean J Med 2015;88:224-230)

증례 : JAK2 돌연변이를 갖는 진성적혈구 증가증과 무증상 다발성 골수종이 동반된 1예

정윤화 ( Yun Hwa Jung ),우인숙 ( In Sook Woo ),한상봉 ( Sang Bong Han ),이제훈 ( Je Hoon Lee ),한치화 ( Chi Wha Han ) 대한내과학회 2013 대한내과학회지 Vol.84 No.2

저자들은 JAK2V617F 돌연변이를 동반한 진성적혈구증가증 환자에서 무증상 다발성골수종이 병발한 증례를 경험하였기에 문헌고찰과 함께 흥미로운 증례로 보고한다. The lymphoproliferative disease multiple myeloma and the myeloproliferative disease polycythemia vera have different pathogenic mechanisms and different natural courses. Thus, the concomitant development of these two diseases in the same individual is rare. In most previously reported cases of both diseases, one disease was assumed to be a secondary malignancy caused by chemotherapy for the other primary disease. Our case was diagnosed as smoldering myeloma based on increased bone marrow plasma cell numbers and monoclonal gammopathy during a regular follow-up visit for JAK2V617F mutation-positive polycythemia vera, which had not been treated except with phlebotomy. This case provides useful clues for understanding the pathogenesis of these two hematological malignancies and the association between them. Here, we report a case of polycythemia vera with a JAK2V617F mutation combined with smoldering myeloma and discuss the clinical significance and pathogenic association between these disorders of different lineages, along with a literature review. (Korean J Med 2013;84:308-312)

피부 백혈병의 임상적 고찰

장인강 ( In Gang Jang ),이동원 ( Dong Won Lee ),한치화 ( Chi Wha Han ),김춘추 ( Chun Chu Kim ),조백기 ( Baik Kee Cho ) 대한피부과학회 1996 대한피부과학회지 Vol.34 No.4

Background: Leukemia cutis is readily recognized and documented by biopsy, in contrast. to leukemic involvement in more occult sites. Nine cases of leukemia cutis have been reported in the Korean literatures. However no collective clinical studies have been reported in Korea. Objective : We evaluated the differences in patient age and sex, the clinical appearences and distributions of the skin lesions, interval between diagnosis of systemic leukemia and skin involvement, clinical course, and prognosis according to the type of leukemias. Methods : We carried out a retvospective study of 22 cases of leukemia cutis. Clinical information was obtained from the records of of 22 patients diagnosed at St. Mary's Hospital from 1988 to 1995. All the included cases were well evaluated for their clinical and histopathologic findings. Results : 1. Among 22 patients with leukemia cutis, male patients outnumbered female by 2 to 1 and the mean age was 25.8 years. 2. The clinical appearance of leukemia cutis includes papules, macules, nodules, plaques in all types of leukemia. Ulcerative lesions and vesicles were seen infrequently in leukemia cutis. Leukemia cutis often involved saultiple location of the skin, with no specific predilection of the site. There were no differences in distribution of lesions depending on the types of systemic leukemia. 3. In 68% of the patients with leukemia cutis, the skin lesions developed after the systemic leukemia was diagnosed, and 14% of patients had concomitant, involvement. 18% of patients had skin lesions preceding the diagnosis of systemic leukemia, howevere cytochemical and cytomorphologic studies of bone marrow and peripheral blood smear were not employed at the time of the skin biopsy. 4. Fourteen of 22 patients(64%) did not achieve a complete remission following the diagnosis of leukemia cutis and two of 14 patients without having complete remission could achieve complete remissions with proper anticancer therapy after the diagnosis of leukemia cutis. Total eight patients(36%) achieved a complete remission, then they had a relapse of leukemia in the skin, without having had any skin involvement at the time of the diagnosis of leukemia. 5. Seventeen of 22 patients(77% ) who were being followed up in our series died after leukemia cutis was diagnosed. The mean intervals between diagnosis of leukemia cutis and death was 3.8 months and they died mostly within 1 year. Conclusion : The presence of leukemic infiltration in the skin may help the clinician suspect the early diagnosis and relapse of systemic leukemia. It appears that leukemia cutis is associated with a grave prognosis. (Kor J Dermatol 1996;34(4): 507-514)

몇가지 관해유도요법제에 의한 급성임파구성 백혈병의 관해율

강진형(Jin Hyoung Kang),진종률(Jong Youl Jin),홍영선(Young Seon Hong),한치화(Chi Wha Han),박종원(Jong Won Park),김춘추(Choon Choo Kim),김동집(Dong Jip Kim),김학기(Hack Ki Kim) 대한내과학회 1987 대한내과학회지 Vol.32 No.5

N/A The case analysis of 74 patients, who were admitted to St. Mary's hospital from Jan, 1982 to Dec. 1986, and had a diagnosis as acute lymphocytic leukemia by bone marrow aspiration and biopsy was conducted. Of all the patients, the number of patients who were treated with VP regimens were 7, VPM regimens 6, VP, L-asp. regimens 4, L2, regimens 28, Modified L, regimens 15, miscellaneous regimens 3 for induction of complete remission. All of them were 63. We could find several interesting informations about the CR rate, duration of CR, survival rate between several prognostic factors. The CR rate in VP regimens was 42.9%, VP. L-asp. regimens 60.7%, L, regimens 67.9%, Modified L, regimen 93.3% According to the FAB classification, there were no difference in CR rate. (L1 76.2%, L2 70.3%, L3 80%) In patients who had CHOP regimen as consolidation, median, duration of CR was longer (6.6 months) than that in patients without CHOP (3.8 months). In the comparison of duration of survival between the immunologic classification, median duration of survival in C-ALL was 12 months and T-ALL was 4.5 months. We might come to conclusion as follows; 1) Modified L2 regimen is superior to other regimens to bring CR. 2) Early consolidation therapy give us more longterm disease free survival. 3) The survival rate of C-ALL is better than that of T-ALL.

주조직적합항원이 불일치하는 마우스 동종 조혈모세포이식에서 IL-2로 유도된 CD4+CD25+ T세포를 이용한 이식편대숙주병의 억제

현재호,정대철,정낙균,박수정,민우성,김태규,최병옥,김원일,한치화,김학기,Hyun, Jae Ho,Jeong, Dae Chul,Chung, Nak Gyun,Park, Soo Jeong,Min, Woo Sung,Kim, Tai Gyu,Choi, Byung Ock,Kim, Won Il,Han, Chi Wha,Kim, Hack Ki 대한면역학회 2003 Immune Network Vol.3 No.4

Background: In kidney transplantation, donor specific transfusion may induce tolerance as a result of some immune regulatory cells against the graft. In organ transplantation, the immune state arises from a relationship between the immunocompromised graft and the immunocompetent host. However, a reverse immunological situation exists between the graft and the host in hematopoietic stem cell transplantation (HSCT). In addition, early IL-2 injections after an allogeneic murine HSCT have been shown to prevent lethal graft versus host disease (GVHD) due to CD4+ cells. We investigated the induction of the regulatory CD4+CD25+ cells after a transfusion of irradiated recipient cells with IL-2 into a donor. Methods: The splenocytes (SP) were obtained from 6 week-old BALB/c mice ($H-2^d$) and irradiated as a single cell suspension. The donor mice (C3H/He, $H-2^k$) received $5{\times}10^6$ irradiated SP, and 5,000 IU IL-2 injected intraperitoneally on the day prior to HSCT. The CD4+CD25+ cell populations in SP treated C3H/He were analyzed. In order to determine the in vivo effect of CD4+CD25+ cells, the lethally irradiated BALB/c were transplanted with $1{\times}10^7$ donor BM and $5{\times}10^6$ CD4+CD25+ cells. The other recipient mice received either $1{\times}10^7$ donor BM with $5{\times}10^6$ CD4+ CD25- cells or the untreated SP. The survival and GVHD was assessed daily by a clinical scoring system. Results: In the MLR assay, BALB/c SP was used as a stimulator with C3H/He SP, as a responder, with or without treatment. The inhibition of proliferation was $30.0{\pm}13%$ compared to the control. In addition, the MLR with either the CD4+CD25+ or CD4+CD25- cells, which were isolated by MidiMacs, from the C3H/He SP treated with the recipient SP and IL-2 was evaluated. The donor SP treated with the recipient cells and IL-2 contained more CD4+CD25+ cells ($5.4{\pm}1.5%$) than the untreated mice SP ($1.4{\pm}0.3%$)(P<0.01). There was a profound inhibition in the CD4+CD25+ cells ($61.1{\pm}6.1%$), but a marked proliferation in the CD4+CD25- cells ($129.8{\pm}65.2%$). Mice in the CD4+CD25+ group showed low GVHD scores and a slow progression from the post-HSCT day 4 to day 9, but those in the control and CD4+CD25- groups had a high score and rapid progression (P<0.001). The probability of survival was 83.3% in the CD4+CD25+ group until post-HSC day 35 and all mice in the control and CD4+CD25- groups died on post-HSCT day 8 or 9 (P=0.0105). Conclusion: Donor graft engineering with irradiated recipient SP and IL-2 (recipient specific transfusion) can induce abundant regulatory CD4+CD25+ cells to prevent GVHD.

마우스 동종 조혈모세포 이식모델에서 Cyclosporin A, FK506, 3-Deazaadenosine 등의 약제가 급성 이식편대 숙주병과 생존에 미치는 영향

진종률,정대철,엄현석,정낙균,박수정,최병옥,민우성,김학기,김춘추,한치화,Jin, Jong Youl,Jeong, Dae Chul,Eom, Hyeon Seok,Chung, Nak Gyun,Park, Soo Jeong,Choi, Byung Ock,Min, Woo Sung,Kim, Hack Ki,Kim, Chun Choo,Han, Chi Wha 대한면역학회 2003 Immune Network Vol.3 No.2

Background: We investigated the effect of donor marrow T cell depletion, administration of FK506, cyclosporin A (CSA), and 3-deazaadenosine (DZA) on graft versus host disease (GVHD) after allogeneic murine hematopoietic stem cell transplantation (HSCT). Methods: We used 4 to 6 week old Balb/c ($H-2^d$, recipient), and C3H/He ($H-2^k$, donor) mice. Total body irradiated recipients received $1{\times}10^7$ bone marrow cells (BM) and $0.5{\times}10^7$ splenocytes of donor under FK506 (36 mg/kg/day), CSA (5 mg/kg/day, 20 mg/kg/day), and DZA (45 mg/kg/day), which were injected intraperitoneally from day 1 to day 14 daily and then three times a week for another 2 weeks. To prevent the GVHD, irradiated Balb/c mice were transplanted with $1{\times}10^7$ rotor-off (R/O) cells of donor BM. The severity of GVHD was assessed daily by clinical scoring method. Results: All experimental groups were well grafted after HSCT. Mice in experimental group showed higher GVHD score and more rapid progression of GVHD than the mice with R/O cells (R/O group) (p<0.01). There were relatively low GVHD scores and slow progressions in FK506 and low dose CSAgroups than high dose CSA group (p<0.01). The survival was better in FK506 group than low dose CSA group. All mice treated with CSA died within 12 days after HSCT. The GVHD score in DZA group was low and slow in comparison with control group (p<0.05), but severity and progression were similar with low dose CSA group (p=0.11). All mice without immunosuppressive treatment died within 8 days, but all survived in R/O group (p<0.01). Survival in low dose CSA group was longer than in control group (p<0.05), but in high dose CSA group, survival was similar to control group. The survival benefit in DZA group was similar with low dose CSA group. FK506 group has the best survival benefit than other groups (p<0.01), comparable with R/O group (p=0.18), although probability of survival was 60%. Conclusion: We developed lethal GVHD model after allogeneic murine HSCT. In this model, immunosuppressive agents showed survival benefits in prevention of GVHD. DZA showed similar survival benefits to low dose CSA. We propose that DZA can be used as a new immunosuppressive agent to prevent GVHD after allogeneic HSCT.