사람의 동종 조혈모세포이식에서 CD4⁺CD25⁺ T세포의 분포와 이식편대숙주병

이대형,정낙균,정대철,조빈,김학기,Lee, Dae Hyoung,Chung, Nak Gyun,Jeong, Dae Chul,Cho, Bin,Kim, Hack Ki 대한소아청소년과학회 2008 Clinical and Experimental Pediatrics (CEP) Vol.51 No.12

목 적: 본 연구의 목적은 사람의 동종 조혈모세포이식에서 공여자의 이식편과 환자의 이식 후 말초혈액에서 $CD4^+CD25^+$ T 세포 분획의 분포를 알아보고 급성 이식편대숙주병(GVHD)과 연관성을 알아보고자 하였다. 방 법: 동종 조혈모세포이식을 시행 받은 17명의 소아를 대상으로 하였다. 공여자의 이식편과 이식 받은 환자의 이식 후 말초혈액으로부터 얻은 검체를 유세포 분석(flow cytometry)하였다. 공여자의 이식편과 이식 후 1개월과 3개월에 환자의 말초혈액 내 $CD4^+CD25^+$ T 세포의 분획과 절대 세포수를 알아보았다. 결 과: 공여자의 이식편 내 $CD4^+CD25^+$ T 세포의 분획은 급성 GVHD 발생군과 비발생군에서 각각 0.90%, 1.06%이었으며 차이가 없었다(P=0.62). 이식편 내 $CD4^+CD25^+$ T세포의 절대수는 급성 GVHD 발생군과 비발생군이 각각 $6.18{\times}10^5/kg$와 $25.85{\times}10^5/kg$으로 급성 GVHD 비발생군이 발생군보다 많은 경향을 보였으나 유의성은 없었다(P=0.09). 급성 GVHD 비발생군의 말초혈액 $CD4^+CD25^+$ T 세포는 이식 후 1개월에 2.11%, 3개월에 1.43%로 유의하게 감소하였으나(P=0.028), 급성 GVHD 발생군의 말초혈액 내 $CD4^+CD25^+$ T 세포는 이식 후 1개월과 3개월에 각각 2.47%와 2.30%로 유의한 차이가 없었다(P=0.50). 결 론: 본 실험을 통하여 저자들은 공여자의 이식편 내 $CD4^+CD25^+$ T세포의 분포와 이식 후 환자의 급성 GVHD의 관계에 대한 유의성은 검증할 수 없었으며 이식 후 환자의 말초혈액 내 $CD4^+CD25^+$ T 세포에는 조절 T세포보다 GVHD와 연관된 활성화된 T세포의 분획이 더 클 것으로 사료되나 추가적인 조절 T세포의 표지자를 이용한 검증이 필요할 것으로 사료된다. Purpose : This study aimed to determine the frequencies of $CD4^+CD25^+$ T cells in donor graft and peripheral blood $CD4^+CD25^+$ T cells in recipients after hematopoietic stem cell transplantation (HSCT) and their association with graft-versus-host disease (GVHD). Methods : Seventeen children who underwent HSCT were investigated. $CD4^+CD25^+$ T cells in samples from donor grafts and recipient peripheral blood were assessed by flow cytometry at 1 and 3 months after transplantation. Results : $CD4^+CD25^+$ T cell frequencies in the grafts showed no significant difference between patients with and without acute GVHD (0.90% vs. 1.06%, P=0.62). Absolute $CD4^+CD25^+$ T cell number in grafts were lower in patients with acute GVHD than in those without acute GVHD ($6.18{\times}10^5/kg$ vs. $25.85{\times}10^5/kg$, P=0.09). Patients without acute GVHD showed a significant decrease in peripheral blood $CD4^+CD25^+$ T cell percentage at 3 months compared to those at 1 month after HSCT (2.11% vs. 1.43%, P=0.028). However, in patients with acute GVHD, $CD4^+CD25^+$ T cell percentage at 3 months was not different from the corresponding percentage at 1 month after HSCT (2.47% vs. 2.30%, P=0.5). Conclusion : The effect of frequencies of $CD4^+CD25^+$ T cells in donor grafts on acute GVHD after HSCT could not be identified, and the majority of peripheral blood $CD4^+CD25^+$ T cells in patients who underwent HSCT may be activated T cells related to acute GVHD rather than regulatory T cells. Further studies with additional markers for regulatory T cells are needed to validate our results.

다발성 뇌결핵종을 동반한 속립결핵 1례

박선영,이정현,정낙균,김진택,정승연,강진한,Park, Sun Yung,Lee, Jung Hyun,Chung, Nak Gyun,Kim, Jin Tack,Chung, Seung Yun,Kang, Jin Han 대한소아감염학회 2000 Pediatric Infection and Vaccine Vol.7 No.2

국내에서 소아의 중증 결핵 환자는 사회경제적 발달과 BCG 백신의 적극적 접종으로 인하여 현저히 빈도수가 감소하였다. 저자들은 BCG 접종을 생후 4주에 실시했음에도 불구하고 가족내의 결핵 환자 발생이 인지되지 않아 조기 치료의 기회를 놓침으로서 속립결핵과 뇌결핵종의 합병증이 유발된 중증 결핵 환아 1례를 경험하였기에 문헌 고찰과 함께 보고하는 바이다. The incidence of tuberculosis has been decreased, and especially the incidence of severe complicated tuberculosis has been markedly decreased as the result of widely used BCG vaccines. But tuberculosis is still an important community accquired infectiouse disease in the world despite continued worldwide efforts to control the disease. Miliary tuberculosis, the most serious complicated tuberculosis, can be occurred by lymphohematogenous dissemination of tuberculosis, and intracranial tuberculoma with or without tuberculosis meningitis can be developed in case of miliary tuberculosis. In general, serious tuberculosis infections such as miliary tuberculosis and CNS tuberculosis are developed especially in young infants and children in cases of delayed diagnosis and treatment despite receiving BCG vaccination, and usually those patients have contact sources. Intrcranial tuberculoma in children are usually found near infratentorial site at the base of cerebellum, and clinically symptoms and signs of increased intracranial pressure developed before treatment. Serial brain CT or MRI is a good non-invasive diagnostic modality of intracranial tuberculoma. Although surgical intervention was initially advocated as the mainstay of intracranial tuberculoma therapy, but many recent clinical studies indicate that intracranial tuberculoma can be cured with medical treatment alone. We experienced a case of 3 months old male patient, who was diagnosed as having miliary tuberculosis associated with multiple intracranial tuberculoma. He received BCG vaccination at 4 weeks after birth, and his father was confirmed as active pulmonary tuberculosis patient after this patient's admission. We report this case with a review of related literatures.

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.

소아 골수이형성 증후군에서 조혈모세포이식의 단기간 결과 분석

이진,김소연,조빈,장필상,정낙균,김학기,Lee, Jin,Kim, Soh Yeon,Cho, Bin,Jang, Pil Sang,Chung, Nak Gyun,Kim, Hack Ki 대한소아청소년과학회 2002 Clinical and Experimental Pediatrics (CEP) Vol.45 No.3

목 적 : 소아의 골수이형성 증후군은 드문 질환군으로 예후가 매우 불량하며 화학요법으로는 완치가 어렵다. 유일한 완치요법으로서 조혈모세포이식이 시행되고 있으나 소아의 경우 증례가 적어 이에 대한 체계적 결과 분석이 빈약한 실정이다. 저자들은 골수이형성증후군에서 조혈모세포이식을 시행한 증례들의 단기간의 결과와 이식합병증들을 분석하고자 하였다. 방 법 : 1995년 11월부터 2001년 1월까지 가톨릭대학교 성모병원 소아과에서 골수이형성 증후군으로 조혈모세포이식을 시행 받은 10명의 환아를 대상으로 하였다. 대상질환은 CMMoL 5례, RAEB 3례, RAEBt 2례이었고, 이식형태는 HLA-일치 형제간 골수이식 4례, 비혈연간 골수이식이 4례, 제대혈 조혈모세포이식이 1례, 가족간 HLA-부분일치 조혈모세포이식이 1례이었다. 전처치로는 BuCy 5례, TBI+BuCy 2례, BuCy+ATG, TBI+Cy 및 TBI+Melphalan이 각각 1례에서 사용되었다. 결 과 : 1) 10명 모두 생착(100%)되었으며 현재 8명(80%)이 무병생존(3-65개월, 정중 추적기간 11개월) 중이다. 2) 이식전처치로 인한 합병증으로 VOD가 3례에서 관찰되었으나 사망한 예는 없었다. 3) II-III도의 급성 이식편대 숙주병은 5례(50%)에서 발생하였으며 II가 4례, III가 1례이었다. 급성 이식 편대 숙주병과 관련된 사망은 없었다. 4) 전체 환아 10례 중 3례에서 이식 후 재발되었으나 1례는 화학요법 후 조혈모세포구제술에 의하여 현재 무병생존 중이며 2례는 사망하였다. 결 론: 소아 골수이형성 증후군에서 조혈모세포이식은 질환을 완치시킬 수 있는 우수한 결과를 보여주고 있으나 아직 증례가 적고 추적기간이 짧아 향후 더 많은 연구가 필요하다. Purpose : In most cases, myelodysplastic syndrome(MDS) transforms into a more aggressive state or acute myelogenous leukemia; it's prognosis is very poor. It is believed that hematopoietic stem cell transplantation(HSCT) is the only curative treatment of MDS, but available data in children are very sparse. In this report, the short term outcome of HSCT in childhood MDS was analyzed. Methods : Ten children with MDS(CMMoL 5, RAEB 3, RAEBt 2) underwent HSCT(HLA-matched sibling transplantation 4, HLA-matched unrelated transplantation 4, cord blood transplantation 1, HLA-mismatched familial transplantation 1) between November 1995 and January 2001 at St. Mary's Hospital. Median follow-up duration was 11 months. Results : Engraftment was successful in all cases and 8 patients are alive without disease. Three cases of VOD were observed and improved without complication. Four cases of grade II and 1 case of grade III acute GVHD were observed and well controlled with treatment. Three patients relapsed after transplantation. One patient is alive without disease after cytoreduction with allogenic stem cell rescue and 2 patients died of relapse. Conclusion : HSCT is a curative strategy of MDS and the survival rate is relatively higher than that of adults. But there is an obvious need for more studies because of the small number of patients and the short duration of the follow-up.

기관기관지 1 례

최정아(Jeong Ah Choi),정낙균(Nak Gyun Chung),이준성(Joon Sung Lee),황경태(Kyung Tai Whang),조성훈(Sung Hoon Cho) 대한소아알레르기호흡기학회 1998 소아알레르기 및 호흡기학회지 Vol.8 No.1

Tracheal bronchus is an aberrant bronchus that arises most often from right tracheal wall above the carina. It is a rare congenital anomaly, which is usually asymptomatic but occasionally associated with recurrent pneumonia, chronic bronchitis and bronchiectasis. Anomalies found in association with tracheal bronchi include respiratory (tracheal hypoplasia, tracheal stenosis, cystic lung lesion), gastrointestinal and musculoskeletal systems. Tracheal bronchus has been diagnosed by conventional tomography, bronchography and bronchoscopy in the past. Technical advances have greatly enhanced the utility of this diagnostic modality. So chest CT, even three-dimensional reconstruction, is of particular importance in the evaluation of mediastinal, pleural and lung parenchymal lesions. We experienced a case of duodenal atresia and tracheal bronchus in 6-month-old child who suffered from recurrent pneumonia and dyspnea. So we report with a brief review and its related literatures.

A Case of Therapy of Aerosolized Ribavirin in a Leukemia Infant with RSV Infection

권효진,오명진,이재욱,정낙균,조빈,김학기,강진한,Kwon, Hyo Jin,Oh, Myung Jin,Lee, Jae Wook,Chung, Nak Gyun,Cho, Bin,Kim, Hack Ki,Kang, Jin Han The Korean Society of Pediatric Infectious Disease 2012 Pediatric Infection and Vaccine Vol.19 No.3

RSV는 2세 미만의 소아에서 급성 하기도 감염으로 인한 입원의 주원인이다. 특히 미숙아, 선천성 심폐질환, 면역결핍이 동반된 경우 주요 위험군으로 알려져 있다. 고위험군의 소아에서 중증 RSV 감염의 경우 리바비린 흡입요법이 허가가 되어 있으나 고비용, 안전성 등의 문제로 국내 임상에서의 사용은 매우 제한적인 실정이다. 저자들은 8개월 여환이 급성 림프구성 백혈병으로 관해유도요법 항암치료 중 발생한 RSV 폐렴으로 기흉, 기종격동, 호흡부전이 동반된 중증 감염을 경험하였다. 정맥용 면역글로불린, 경구 리바비린 투여에 반응이 없어 리바비린 흡입 치료를 시행하였고, 이후 임상적 호전을 경험하였기에 보고하는 바이다. Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infection in infants. Life-threatening RSV infection is often reported in young children and immunocompromised hosts. Since there is no report on ribavirin therapy for RSV pneumonia in pediatric cancer patients in Korea, we report one case of RSV pneumonia that developed in an infant with acute lymphoblastic leukemia (ALL). Despite administration of oral ribavirin and intravenous immunoglobulin, the patient's respiratory distress worsened and admission to an intensive care unit was necessary. Chest x-ray showed multifocal consolidation, pneumothorax, and pneumomediastinum. Treatment with aerosolized ribavirin led to significant clinical improvement. The role of aerosolized ribavirin is still controversial, but it might have a therapeutic potential for severe RSV pneumonia in children with leukemia.

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.

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)

동종 골수이식 후 후기 거부반응을 보인 재생불량성 빈혈환아에서 동종 G-CSF 가동화 말초혈 조혈모세포이식 후 생착을 보인 1례

정낙균,조빈,정대철,김학기 대한조혈모세포이식학회 1998 대한조혈모세포이식학회지 Vol.3 No.1

중증 재생불량성 빈혈의 가장 효과적인 치료는 조직적합성 항원이 일치하는 형제자매의 골수이식이지만 골수이식 후에 거부반응으로 기대한 효과를 보지 못하는 경우 구제요법으로 수년 전까지만 해도 면역억제를 목적으로 방사선을 포함한 강력한 전처치 후에 동종 골수이식을 재시행 하였으나 성공률이 떨어지며 전처치로 인해 심각한 부작용을 초래하는 등 문제점이 있었다. 그러나 최근에는 가동화된 말초혈 조혈모세포이식이 보편화됨에 따라 동종 골수이식 후 생착부전이 있는 경우 강력한 전처치없이 재차 가동화된 말초혈 조혈모세포를 이식하는 방법으로 생착에 성공한 사례들이 국내외에서 보고되고 있으며, 특히 가동화된 말초혈 조혈모세포이식은 골수이식의 경우보다 조기 생착을 보이며 면역적인 면에서도 빠른 회복을 보이는 것으로 알려져 있다. 저자들은 동종 골수이식 후 후기 거부반응을 보인 중증 재생불량성 빈혈 환아에서 골수 공여자에게 G-CSF를 투여하여 가동화된 말초혈 조혈모세포를 이식하여 구제요번에 성공한 1례를 경험하여 보고하는바이다. 환아는 내원 4년7개월 전 중등도 재생불량성 빈혈로 진단되어 본원에서 항림프구 글로불린으로 치료 받았으며 치료 3개월 후 완전관해를 보였으나 18개월 이후 다시 악화되며 중증 재생불량성 빈혈의 소견을 보였다. 남동생과 조직적합성 항원이 일치하여 procarbazine, 항흉선세포 글로불린 및 cyclophosphamide 로 전처치 후 내원 17개월 전 동종 골수이식을 시행하였다. 환자에게 주입된 세포수로는 단핵구는 1.09×10^(8)/㎏, CD34+세포는 6.65×10^(6)/㎏이었으며 이식편대숙주반응을 예방하기 위하여 CSA와 methotrexate를 사용하였다. 이식 후 7개월까지는 급성 및 만성 이식편대숙주반응없이 성공적인 생착 소견을 보였으나 이후 혈소판의 수치가 감소하기 시작하면서 12개월 이후에는 다시 수혈이 필요한 정도로 전혈구의 수가 감소하였다. 입원직전 시행한 골수검사에서도 적혈구,백혈구, 혈소판들의 전구세포들이 모두 관찰되기는 하나 세포밀도가 20%이하로 감소되어있었으며 PCR-RFLP검사에서도 지속적으로 공여자와 환아의 혼합된 양상으로 나타나는 후기 거부반응의 소견을 보였다. 구제요법으로 골수이식과 동일한 공여자로부터 G-CSF가동화된 말초혈 조혈모세포이식을 시행하기위해 전처치로 750 cGy의 total nodal irradiation (TNI)를 시행하고 ATG를 4일간 투여하였다. 환아에게 ATG를 투여하기 시작한 다음날부터 공여자에게는 rhG-CSF(GrasynR)를 10㎍/㎏/day의 용량으로 6일간 투여하였으며 투여 5일째부터 말초혈에서 조혈모세포 및 단핵구를 3일에 걸쳐 채집하여 환자의 중심정맥을 통하여 투여하였다. G-CSF를 투여하고 조혈모 세포를 채집하는 기간중 공여자에게 특별한 이상 소견은 없었으며 환아에게 이식된 단핵구 및 CD34+ 조혈모세포수는 각각 환아의 몸무게 ㎏당 18.5×10^(8), 14.7×10^(6)이었다. 이식편대 숙주반응을 예방하기 위하여 CSA를 사용하였으며 이식 후 3일부터 말초혈액 백혈구수가 1,000/㎣으로 증가하였다. 이식 5일 후부터 GM-CSF 250㎍을 환아에게 피하 주사하였으며 이식 12일 이후 특별한 수혈 없이 혈소판수가 50,000/㎣이상으로 계속 유지되었고 이식편대 숙주반응은 나타나지 않았다. 이식 후 21일에 시행한 골수검사에서도 세포밀도 80%에 적혈구, 백혈구, 혈소판들의 전구세포들이 모두 관찰되는 생착 소견을 보였다. 환아는 이후 급성 이식편대 숙주반응 등의 특별한 이상소견 없이 이식 후 2개월이 지난 현재까지 건강하게 지내고 있다. 저자들은 동종 골수이식 후 후기 거부반응을 보인 재생불량성 빈혈 환아에서 TNI 및 ATG로 전처치 후 공여자에게 G-CSF를 투여하여 가동화된 말초혈 조혈모세포를 이식하여 생착을 보인 1례를 경험하였기에 문헌고찰과 함께 보고하는 바이다. Allogeneic bone marrow transplantation (BMT) from HLA-identical siblings is the treatment of choice in children with severs aplastic anemia(SAA). However, insufficient graft function owing to rejection remains an important and life-threatening complication following BMT for SAA. In that case, recent clinical studies have shown more rapid engraftment and faster recovery of the immune system after allogeneic transplantation of peripheral blood stem cells (PBSC) compared with BMT for the treatment of graft rejection. Here we report a case of successful transplatation of allogeneic granulocyte colony-stimulating factor (G-CSF) mobilized PBSC after engraftment failure of allogeneic BMT. A 7-year old male underwent allogeneic BMT for SAA from his HLA-and blood groupidentical brother. He was conditioned with cyclophosphamide, procarbazine and anti-thymocyte globulin (ATG, PAsteur). Post-transplant immunosuppression for graft versus host disease(GVHD) consisted of cyclosporine A (CSA) and a short course of methotrexate. Initially, the engraftment was sucessful until 7 months after BMT without any sign of acute and chronic GVHD. However, he failed to achieve durable trilineage hematopoietic engraftment. Evaluation of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) revealed mixed chimerism. 17 months after the first BMT, G-CSF primed PBSC from the same donor (cell dose 18.5×10^(8)/㎏ mononuclear, 14.7×10^(6)/㎏ CD34^(+) cells) was given after preparation with ATG and total nodal irradiation (TNI, 750 cGy). No side effects related to G-CSF administration or apheresis were observed in the donor. CSA was used for GVHD prophylaxis. To promote marrow recovery, granulocyte-macrophage CSF (GM-CSF, 250㎍/㎡) was administered from day +5 after the PBSC transfusion. The WBC count exceeded 1,000/㎣ on day +3 and the platelet count exceeded 50,000/㎣ on day +12 without transfusion. On day +21, BM histology showed a cellularity of 80% with trilineage engraftment. The patient is currently well with a stable engraftment 2 months following allogeneic PBSCT, without any sign of acute GVHD.

소아 동종 조혈모세포이식 200예의 분석 : Single Center Study

김학기,조빈,정낙균,정대철,장필상,김선영,김춘추 대한조혈모세포이식학회 2002 대한조혈모세포이식학회지 Vol.7 No.1

연구배경: 1983년 11월부터 2000년 9월까지 시행한 동종 조혈모세포이식의 성적을 분석하여 소아 골수이식의 발전 방향을 모색하고자 하였다. 방법: 1983년 11월부터 2000년 9월까지 가톨릭의대 조혈모세포이식센터, 성모병원 소아과에서 동종 조혈모세포이식을 시행한 200예를 대상으로 조혈모세포이식의 유형 및 대상질환, 이식 당시의 상태 및 전처치에 따른 치료 성적을 후향적으로 분석하였다. 결과: 200예 중 HLA-일치 형제간 골수이식이 146예(73%), HLA-일치 형제간 골수이식 이외의 이식이 54예(27%)였다. 1) HLA-일치 형제간 골수이식: 146예 중 남아와 여아가 각각 78명과 68명이었으며 SAA 50예의 5년 무병 생존율은 95.8±2.9%였고 AML 45예의 5년 무병 생존율은 71.7±7.0%로 일차 및 이차 관해기에 이식 받은 40예와 5예의 5년 무병 생존율은 각각 73.6±7.2%와 60.0±21.9%였다. AML에서 전처치로 Bu/Cy를 사용한 28예와 TBI/Cy를 사용하였던 9예의 5년 무병 생존율은 각각 81.9±7.4%와 33.3±15.7%였으며 Bu/Cu/TBI를 시행한 8예의 무병 생존율은 80.0±17.9%였다. ALL 33예의 5년 이상 무병 생존율은 75.5±7.5%였고 일차 및 이차 관해기에 이식을 시행하였던 18예와 14예의 무병 생존율은 각각 83.0±9.0%와 71.4±12.1%였다. CML 및 MDS 11예의 5년 무병 생존율은 72.7±13.4%였다. 기타 질환으로는 Fanconi 빈혈 2예, 혈구탐식성 조직구증식증 2예, 순적혈구 빈혈 2예, Kostmann 증후군이 1예로 이들의 전체 무병 생존율은 85.7±13.2%였다. 2) HLA-일치 형제간 골수이식 이외의 이식을 시행하였던 54예의 3년 이상 무병 생존율은 45.3±11.6%였으며 HLA-일치 UBMT 26예, CBSCT 15예, 형제 이외의 혈연에 의한 골수이식이 13예로 이들의 무병 생존율은 각각 56.2±10.8%, 58.2±13.1%, 35.9±17.3%였다. 결론: 소아 난치성 혈액질환의 완치요법으로 동종 골수이식의 치료효과를 확인할 수 있었으며, 동종 조혈모세포의 공여원으로 비혈연간 골수나 제대혈의 이용이 점차 증가하고 있음을 알 수 있었다. Background: Bone marrow transplantation was first introduced to Korean children in 1983. Since then the number of children receiving transplants has increased steadily. Methods: We analyzed two hundred pediatric cases of allogeneic hematopoietic stem cell transplantation between Nov. 1983 and Sep. 2000 in Catholic Hematopoietic Stem Cell Transplantation Center of Korea. Results: HLA-matched sibling transplantations were performed in 146 cases (78 males, 68 females, median age; 10 years) with median follow-up of 47 months. The 3-year estimated event-free survival (EFS) of ALL and AML was 76% and 72% respectively. The 5-year estimated EFS of severe aplastic anemia and CML/MDS was 96% and 73% respectively. The 2-year estimated EFS of nonmalignant rare disease was 86%. Twenty-six children underwent unrelated bone marrow transplantation (UBMT), 15 cord blood stem cell transplanta-tion (CBSCT) and 13 familial haploidentical transplantation (FHT). There were 35 males and 19 females with a median age of 6.5 years and median follow-up of 18.5 months. The estimated 2-year EFS of UBMT, CBSCT and FHT were 56%, 58% and 34% respectively. Conclusion: HLA-matched sibling allogeneic BMT showed better survival in children with hematopoietic stem cell disorder compared to UBMT and CBSCT. Recently, transplants using alternative stem cell source are increasing due to lack of suitable matched sibling donor and continuous efforts for reducing transplant-related complications are warranted for improving survival.