• Clinical and Experimental Pediatrics
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• v.55 no.3
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• pp.93-99
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• 2012

Purpose: This study compared outcomes in children with acute leukemia who underwent transplantations with umbilical cord blood (UCB), bone marrow, or peripheral blood stem cells from a human leukocyte antigen (HLA)-matched related donor (MRD) or an unrelated donor (URD). Methods: This retrospective study included consecutive acute leukemia patients who underwent their first allogeneic hematopoietic stem cell transplantation (HSCT) at Samsung Medical Center between 2005 and 2010. Patients received stem cells from MRD (n=33), URD (n=46), or UCB (n=41). Results: Neutrophil and platelet recovery were significantly longer after HSCT with UCB than with MRD or URD ($p$ <0.01 for both). In multivariate analysis using the MRD group as a reference, the URD group had a significantly higher risk of grade III to IV acute graft-versus-host disease (GVHD; relative risk [RR], 15.2; 95% confidence interval [CI], 1.2 to 186.2; $p$=0.03) and extensive chronic GVHD (RR, 6.9; 95% CI, 1.9 to 25.2; $p$ <0.01). For all 3 donor types, 5-year event-free survival (EFS) and overall survival were similar. Extensive chronic GVHD was associated with fewer relapses (RR, 0.1; 95% CI, 0.04 to 0.6; $p$ <0.01). Multivariate analysis showed that lower EFS was associated with advanced disease at transplantation (RR, 3.2; 95% CI, 1.3 to 7.8; $p$ <0.01) and total body irradiation (RR, 2.1; 95% CI, 1.0 to 4.3; $p$=0.04). Conclusion: Survival after UCB transplantation was similar to survival after MRD and URD transplantation. For patients lacking an HLA matched donor, the use of UCB is a suitable alternative.

• BMB Reports
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• v.49 no.4
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• pp.197-198
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• 2016

Although three different research groups have reported successful derivations of human somatic cell nuclear transfer-derived embryonic stem cell (SCNT-ESC) lines using fetal, neonatal and adult fibroblasts, the extremely poor development of cloned embryos has hindered its potential applications in regenerative medicine. Recently, however, our group discovered that the severe methylation of lysine 9 in Histone H3 in a human somatic cell genome was a major SCNT reprogramming barrier, and the overexpression of KDM4A, a H3K9me3 demethylase, significantly improved the blastocyst formation of SCNT embryos. In particular, by applying this new approach, we were able to produce multiple SCNT-ES cell lines using oocytes obtained from donors whose eggs previously failed to develop to the blastocyst stage. Moreover, the success rate was closer to 25%, which is comparable to that of IVF embryos, so that our new human SCNT method seems to be a practical approach to establishing a pluripotent stem cell bank for the general public as well as for individual patients.

• Development and Reproduction
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• v.23 no.2
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• pp.79-92
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• 2019

Humanized mice, containing engrafted human cells and tissues, are emerging as an important in vivo platform for studying human diseases. Since the development of Nod scid gamma (NSG) mice bearing mutations in the IL-2 receptor gamma chain, many investigators have used NSG mice engrafted with human hematopoietic stem cells (HSCs) to generate functional human immune systems in vivo, results in high efficacy of human cell engraftment. The development of NSG mice has allowed significant advances to be made in studies on several human diseases, including cancer and graft-versus-host-disease (GVHD), and in regenerative medicine. Based on the human HSC transplantation, organ transplantation including thymus and liver in the renal capsule has been performed. Also, immune reconstruction of cells, of the lymphoid as well as myeloid lineages, has been partly accomplished. However, crosstalk between pluripotent stem cell derived therapeutic cells with human leukocyte antigen (HLA) mis/matched types and immune CD3 T cells have not been fully addressed. To overcome this hurdle, human major histocompatibility complex (MHC) molecules, not mouse MHC molecules, are required to generate functional T cells in a humanized mouse model. Here, we briefly summarize characteristics of the humanized mouse model, focusing on development of CD3 T cells with MHC molecules. We also highlight the necessity of the humanized mouse model for the treatment of various human diseases.

• Clinical and Experimental Pediatrics
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• v.48 no.2
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• pp.178-185
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• 2005

Purpose : The purpose of this study was to evaluate the outcome of children with juvenile myelomonocytic leukemia(JMML) treated with allogeneic hematopoietic stem cell transplantation(allo-HSCT). Methods : Eleven JMML patients aged 8-39 months underwent allo-HSCT. The sources of grafts were unrelated donors(n=7), HLA-matched siblings(n=3) and an HLA 1-antigen mismatched familial donor. All patients had received chemotherapy ${\pm}13$-cis-retinoic acid(CRA) before transplant, and CRA was used, posttransplant, in six patients. Results : Only three patients were in complete remission(CR) at the time of transplantation. Initial chimeric status revealed complete donor chimerism(CC) in five patients, mixed chimerism(MC) in five and autologous recovery(AR) in one. One patient with MC having persistent splenomegaly eventually turned to CC and CR after rapid tapering of cyclosporine, combined with daily use of CRA. An AR case relapsed shortly after transplant but was rescued with second, unrelated cord blood transplantation. Ultimately, six patients are alive, event-free, with a median follow-up of 15.5 months posttransplant. All three deaths occurred in patients who failed to achieve CC, leading to disease progression. Conclusion : We suggest that graft-versus-leukemia effect play an important role and CRA a possible role in posttransplant leukemic involution in JMML. In patients whose leukemic burden is still high with MC after transplant, early tapering of immunosuppressants and introduction of CRA might provide a chance of a cure for some patients.

• Journal of Chest Surgery
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• v.30 no.2
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• pp.164-171
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• 1997

Heart transplantation is now accepted as a definitive therapeutic modality in patients with terminal hear failure. The first successful heart transplantation in humans was done in 1967 and the first case in Korea was performed in november, 1992. Since the first case in 1992, more than 50 cases have been performed in Korea. A total of 20 patients underwent orthotopic heart transplantation since November, 1992 in Asan Medicla Center. The purpose of this study is to evaluate the early results and the follow-up course of 20 cases of heart transplantation done in Asan Medical Center. The average age of 20 patients was 39.9$\pm$11.8 years old(20~58). The mean follow-up duration was 14.4$\pm$11.2 months(1~41). All patients are alive till now. The blood type was identical in 14 and compatible in 6 patients. ihe original heart disease was dilated cardiomyopathy in 16, valvular heart disease in 2, ischemic cardiomyopathy in 1, and giant cell myocarditis in 1 patient. HLA cross matching for recipient and donor was done in 18 cases and the results were negative for T-cell and B-cell in 16 patients, pos tive for warm B-cell in 2 patients. Among 6 loci of A, B, and DR, one locus was matched in 8 cases, 2 loci in 5 cases, and 3 loci matched in 1 case. The number of acute allograft rejection averaged 2.8$\pm$0.5 (0~6) per case and the number of acute allograft rejection requiring treatment averaged 1.0$\pm$0.9 (1~3) per case. The time interval from operation to the first acute rejection requiring treatment was 35.5$\pm$20.4 days (5~60). Acute humoral rejection was suspected strongly in 1 case and was successfully treated. The left ventricular ejection fraction measured by echocardiography and/or MUGA scan was dramatically increased from 17.5$\pm$6.8 (9~32)% to 58.9$\pm$2.0 (55~62)% after heart transplantation. Temporary pacing was needed in 5 patients over 24 hours but normal sinus rhythm appeared within 7 days in all cases. One patient has been taken permanent pacemaker implantation due to complete AV block appearing 140 days after heart transplantaion. One patient had cyclosporine-associated n urotoxicity during the immediate postoperative period and was recovered after 27 hours. The heart transplantation of Asan Medical Center is on a developing stage but the early result is comparable to that of well established centers in other countries, even though the long-term follow-up result must be reevaluated. We can conclude that the heart transplantion is a promising therapeutic option in patients with terminal heart failure.

• Clinical and Experimental Pediatrics
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• v.49 no.2
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• pp.173-180
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• 2006

Purpose : Cytomegalovirus(CMV) infection still remains as a major cause of morbidity and mortality after stem cell transplantation. In this study, we analyzed the results of antigenemia-guided preemptive therapy among children with allogeneic hematopoietic stem cell transplantation to determine the incidence and risk factors associated with CMV antigenemia, and evaluated the efficacy of the CMV antigenemia based preemptive therapy. Methods : We enrolled 213 pediatric patients following allogeneic hematopoietic stem cell transplantation(HSCT), at the Catholic HSCT center between October 1998 and December 2003. Pre-emptive ganciclovir was started when more than 5 CMV Ag-positive cells were detected in matched sibling HSCT, and when any Ag-positive cells were seen in unrelated allogenic HSCT. Results : CMV antigenemia was observed in 88(41.3 percent) of 213 patients on median day 28(day 11-99). In univariated analysis, use of unrelated donors(other than siblings), age of recipient(more than 5 years at transplant) at transplantation, the presence of recipient CMV-IgG before transplantation, TBI-based conditioning regimen and the presence of acute GvHD(grade ${\geq}II$) were the risk factors for positive CMV antigenemia. In multivariate analysis, unrelated bone marrow transplantation, positive recipient CMV serology and acute GvHD(grade ${\geq}II$) were the independent risk factors for positive CMV antigenemia. Conclusion : Risk factors of CMV infection in children were CMV serostatus of the recipient, the source of stem cells, and acute graft-versus-host disease. The pre-emptive therapy based on CMV antigenemia was effective in the prevention of CMV disease.

• Radiation Oncology Journal
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• v.10 no.2
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• pp.247-253
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• 1992

Between August 1987 and July 1991, 22 patients with acute nonlymphocytic leukemia have received allogeneic bone marrow transplantation (BMT) with non-T-lymphocyte-depleted marrow obtained from matched sibling donors. Of these patients, 12 patients were in first complete remission (CR) and 10 patients in second CR or greater or in relapse. All patients were treated with a preparative regimen consisting of cyclophosphamide (CTX, 60 mg/kg) or combined drugs, and 850 cGy single-dose or $150\~200$ cGy fractionated total body irradiation (TBI) administered twice daily for a total dose of $1200\~1320$ cGy. Survivors have been followed from 8 to 64.5 months (median, 24 months). The overall 2 year survival rate, relapse rate and incidence of radiation pneumonitis and graft versus host disease (GVHD) have been evaluated by age, phase of disease, initial WBC count, modality of TBI or conditioning chemotherapy. Overall 2 year survival was $58{\%}$. The median survival was 31 months and mean survival was 23.2 months. Overall survival have significant impact in patients of age >19 years old (p=0.008), patients in first CR (p=0.09). Two year survival rate is significantly correlated with age ( >19 vs $\leqq$19, $79.4\%$ vs $14.3\%$, p=0.0008), regimen of chemotherapy (CTX vs combined drug, $76.9\%\;vs\;33.3\%$, p=0.04), phase of disease (1st CR vs \geqq2nd$ CR or relapse, $83.3\%\;vs\;30\%$, p=0.01) and method of TBI (fractionated vs single dose, $70.7\%\;vs\;37.5\%$, p=0.05). The influence of French-American-British (FAB) subtypes on relapse rate is not significant, but initial WBC count > 20000/$mm^3$ is associated with increased relapse rate. There is difference in the rate of radiation pneumonitis ($14.3\%\;vs\;25\%$), GVHD ($14.3\%\;vs\;50\%$) and relapse ($21.4\%\;vs\;50\%$) according to fractionated versus single-dose TBI. As mentioned above, fractionated TBI is compatible for the preparative regimen combined with chemotherapy En allogeneic BMT of first CR patients under 41 years of age with suitable donor. Those results from a retrospective, non-randomized study clearly need additional clinical data, ideally from a randomized study.