• BLOOD RESEARCH
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• v.53 no.4
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• pp.288-293
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• 2018

Background Although allogeneic hematopoietic cell transplantation (HCT) is the only curative treatment option for myelodysplastic syndrome (MDS), a substantial number of patients experience relapse. We reviewed the clinical outcomes of patients with MDS who relapsed after allogeneic HCT. Methods Thirty patients who experienced relapse or progression after allogeneic HCT for MDS between July 2000 and May 2016 were included in this retrospective analysis. Results The median time from HCT to relapse was 6.6 (range, 0.9-136.3) months. Donor lymphocyte infusions (DLIs) were administered to four patients: one achieved complete remission (CR) and survived disease free, while three did not respond to DLI and died. Hypomethylating agents were administered to seven patients: one who had stable disease continuously received decitabine, while six died without response to treatment. Six patients received AML-like intensive chemotherapy, and three achieved CR: two underwent second HCT and one DLI. One patient receiving second HCT survived without disease, but the other two relapsed and died. Three, four, and eight patients who did not respond to intensive chemotherapy, low-dose cytarabine, and best supportive care, respectively, died. One patient who underwent second HCT following cytogenetic relapse survived disease free. Median overall survival after relapse was 4.4 months, and relapse within 6 months after HCT was associated with shorter survival. Conclusion Outcomes of MDS patients relapsing after allogeneic HCT were disappointing. Some patients could be saved using DLI or second HCT.

• 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.

• The Korean journal of internal medicine
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• v.39 no.1
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• pp.34-56
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• 2024

Acute lymphoblastic leukemia (ALL) is one of the most rapidly changing hematological malignancies with advanced understanding of the genetic landscape, detection methods of minimal residual disease (MRD), and the development of immunotherapeutic agents with good clinical outcomes. The annual incidence of adult ALL in Korea is 300-350 patients per year. The WHO classification of ALL was revised in 2022 to reflect the molecular cytogenetic features and suggest new adverse-risk subgroups, such as Ph-like ALL and ETP-ALL. We continue to use traditional adverse-risk features and cytogenetics, with MRD-directed post-remission therapy including allogeneic hematopoietic cell transplantation. However, with the introduction of novel agents, such as ponatinib, blinatumomab, and inotuzumab ozogamicin incorporated into frontline therapy, good MRD responses have been achieved, and overall survival outcomes are improving. Accordingly, some clinical trials have suggested a possible era of chemotherapy-free or transplantation-free approaches in the near future. Nevertheless, relapse of refractory ALL still occurs, and some poor ALL subtypes, such as Ph-like ALL and ETP-ALL, are unsolved problems for which novel agents and treatment strategies are needed. In this review, we summarize the currently applied diagnostic and therapeutic practices in the era of advanced genetic analysis and targeted immunotherapies in United States and Europe and introduce real-world Korean data.

• Molecules and Cells
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• v.24 no.1
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• pp.1-8
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• 2007

Natural killer (NK) cells play a crucial role in innate immune system and tumor surveillance. NK cells are derived from $CD34^+$hematopoietic stem cells and undergo differentiation via precursor NK cells in bone marrow (BM) through sequential acquisition of functional surface receptors. During differentiation of NK cells, many factors are involved including cytokines, membrane factors and transcription factors as well as microenvironment of BM. NK cells express their own repertoire of receptors including activating and inhibitory receptors that bind to major histocompatibility complex (MHC) class I or class I-related molecules. The balance between activating and inhibitory receptors determines the function of NK cells to kill targets. Binding of NK cell inhibitory receptors to their MHC class I-ligand renders the target cells to be protected from NK cell-mediated cytotoxicity. Thus, NK cells are able to discriminate self from non-self through MHC class I-binding inhibitory receptor. Using intrinsic properties of NK cells, NK cells are emerging to apply as therapeutic agents against many types of cancers. Recently, NK cell alloactivity has also been exploited in killer cell immunoglobulin-like receptor mismatched haploidentical stem cell transplantation to reduce the rate of relapse and graft versus host disease. In this review, we discuss the basic mechanisms of NK cell differentiation, diversity of NK cell receptors, and clinical applications of NK cells for anti-cancer immunotherapy.

• Journal of Korean Academy of Fundamentals of Nursing
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• v.13 no.3
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• pp.428-436
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• 2006

Purpose: To investigate the levels of uncertainty and anxiety at admission and discharge to the isolation unit for patients undergoing hematopoietic stem cell transplantation (HSCT). Method: The data were collected from 60 patients who were admitted to the department of HSCT. Uncertainty and anxiety were assessed using the Mishel Uncertainty in Illness Scale (MUIS) and Anxiety Inventory (STAI). Collected data were analyzed using the SAS program. Results: The mean score for anxiety at admission was 2.20, and at discharge 2.10. The mean score for uncertainty at admission was 2.19, and at discharge 2.07. The anxiety at admission the group with physical discomfort was higher than that of group without physical discomfort. A positive relationship was found between anxiety and uncertainty at admission and at discharge. The major variables were expectation for cure and physical discomfort, explaining 25.87% of the anxiety at admission. The major variable was expectation for cure, explaining 20.94% of the uncertainty at admission. Conclusion: Front the above results, it can be concluded that support and consideration are required to reduce anxiety of the inpatient in single room.

• Journal of mucopolysaccharidosis and rare diseases
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• v.3 no.1
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• pp.14-19
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• 2017

Lysosomal storage diseases (LSDs) are a group of rare inherited metabolic disorders caused by the deficiency of specific lysosomal enzymes and subsequent accumulation of substrates. Enzyme deficiency leads to progressive intra-lysosomal accumulation of the incompletely degraded substances, which cause dysfunction and destruction of the cell and eventually multiple organ damage. Patients have a broad spectrum of clinical phenotypes which are generally not specific for some LSDs, leading to missed or delayed diagnosis. Due to the availability of treatment including enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation for some LSDs, early diagnosis is important. ERT products have been approved with optimal outcomes for some LSDs in the recent decades, including Gaucher, Fabry, mucopolysaccharidosis (MPS) I, Pompe, MPS VI, MPS II, and MPS IVA diseases. ERT can stabilize the clinical condition, prevent disease progression, and improve the long-term outcome of these diseases, especially if started prior to irreversible organ damage. Based on the availability of therapy and suitable screening methods in the recent years, some LSDs, including Pompe, Fabry, Gaucher, MPS I, MPS II, and MPS VI diseases have been incorporated into nationwide newborn screening panels in Taiwan.

• IMMUNE NETWORK
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• v.15 no.3
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• pp.125-134
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• 2015

Acute graft-versus-host-disease (GVHD) is characterized by selective damage to the liver, the skin, and the gastrointestinal tract. Following allogeneic hematopoietic stem cell transplantation, donor bone marrow (BM) cells repopulate the immune system of the recipient. We previously demonstrated that the acute intestinal GVHD (iGVHD) mortality rate was higher in MyD88-deficient BM recipients than that in the control BM recipients. In the present study, the role of MyD88 (expressed by donor BM) in the pathophysiology of hepatic GVHD (hGVHD) was examined. Unlike iGVHD, transplantation with MyD88-deficient T-cell depleted (TCD) BM attenuated hGVHD severity and was associated with low infiltration of T cells into the liver of the recipients. Moreover, GVHD hosts, transplanted with MyD88-deficient TCD BM, exhibited markedly reduced expansion of $CD11b^+Gr-1^+$ myeloidderived suppressor cells (MDSC) in the liver. Adoptive injection of the MDSC from wild type mice, but not MyD88-deficient mice, enhanced hepatic T cell infiltration in the MyD88-deficient TCD BM recipients. Pre-treatment of BM donors with LPS increased MDSC levels in the liver of allogeneic wild type BM recipients. In conclusion, hGVHD and iGVHD may occur through various mechanisms based on the presence of MyD88 in the non-T cell compartment of the allograft.

• Radiation Oncology Journal
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• v.21 no.3
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• pp.192-198
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• 2003

Purpose: Current results of autologous stem cell transplantation (SCT) suggest that this procedure may prolong disease free survival In patients with acute myeloid leukemia (AML). Autologous SCT is increasingly used as treatment for AML in first remission. The aim of this study was to evaluate the outcome of autologous SCT for patients with AML in first remission treated by autologous SCT using cytarabine, melphalan and total body irradiation (TBI) as the conditioning regimen. Materials and Methods: Between January 1995 and December 1999, 29 patients with AML in first remission underwent autologous SCT. The median age of patients was 33 years (range, 16 to 47). The conditioning regimen consisted of cytarabine ($3.0\;gm/m^2$ for 3 days), melphalan ($100\;gm/m^2$ for 1 day) and TBI (total 1000 cGy in five fractions over 3 days). Results: The median follow up was 40 months with a range of 3 to 58 months. The 4-year cumulative probability of disease free survival was 69.0%, and median survival was 41.5 months. The 4-year relapse rate was 27.6%. The factor Influencing disease free survival and relapse rate was the French-American-British (FAB) classification ($M_3$ group vs. other groups; p=0.048, p=0.043). One patient died from treatment-related toxicity. Conclusion:: Although the small number of patients does not allow us to draw any firm conclusion, our results were encouraging and suggest that the association of cytarabine, melphalan and TBI as a conditioning regimen for autologous SCT for AML on first remission appears to be safe and effective.

• Biomedical Science Letters
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• v.18 no.2
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• pp.131-138
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• 2012

Autologous peripheral blood stem cell transplantation (PBSCT) has been used as a major treatment strategy for hematological malignancies. The number of CD34 positive cells in the harvested product is a very important factor for achieving successful transplantation. We studied the factors that can predict the number of CD34 positive cells in the harvested product of acute myelocytic leukemia (AML), multiple myeloma (MM) and Non-Hodgkin's lymphoma (NHL) patients after mobilizing them with chemotherapy plus G-CSF. A total of 73 patients (AML 19 patients, MM 28 patients, NHL 26 patients) with hematological malignancies had been mobilized with chemotherapy and granulocyte colony-stimulating growth factor from April, 2000 to February, 2012. Group's characteristics, checkup opinion of pre-peripheral blood on the day of harvest & outcome of PBSC were analyzed and evaluated using SPSS statistics program after grouping patients as below; group 1: CD34 cell counts < $2{\times}10^6/kg$ (n=16); group 2: $2{\times}10^6/kg{\leq}CD34$ cell counts < $6{\times}10^6/kg$ (n=32); group 3: CD34 cell counts ${\geq}6{\times}10^6/kg$ (n=25). We analyzed the clinical characteristics, the peripheral blood (PB) parameters and the number of CD34 positive cells in the PB and their correlation with the yield of CD34 positive cells collected from the mobilized patients. The total number of leukapheresis sessions was 263 (mean: 3.55 session per patient), and the mean number of harvested CD34 positive cells per patient was $7.37{\times}10^6/kg$. The number of CD34 positive cells in product was significantly correlated with the number of platelet and CD34 positive cells in peripheral blood (P<0.05). The number of PB CD34 positive cells was the best significant factor for the quantity of harvested CD34 positive cells on the linear regression analysis (P<0.05). Many factors could influence the mobilization of peripheral blood stem cells. Platelet count and PB CD34 positive cells count were the two variables which remained to be significant in multivariate analysis. Therefore, the number of platelet and CD34 positive cells in peripheral blood on the day of harvest can be used as an accurate predictor for successful peripheral blood stem cell collection.

• 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.