• Asian Pacific Journal of Cancer Prevention
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• 제16권8호
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• pp.3137-3140
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• 2015

Objective: To explore the immune reconstitution of $CD4^+T$ cells after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and its relationship with invasive fungal infection (IFI) in patients with hematological malignancies. Materials and Methods: Forty-seven patients with hematological malignancies undergoing Allo-HSCT in Binzhou Medical University Hospital from February, 2010 to October, 2014 were selected. At 1, 2 and 3 months after transplantation, the immune subpopulations and concentration of cytokines were assessed respectively using flow cytometry (FCM) and enzyme linked immunosorbent assay (ELISA). The incidence of IFI after transplantation and its correlation with immune reconstitution of $CD4^+T$ cells were investigated. Results: The number of $CD4^+T$ cells and immune subpopulations increased progressively after transplantation as time went on, but the subpopulation cell count 3 months after transplantation was still significantly lower than in the control group (p<0.01). In comparison to the control group, the levels of interleukin-6 (IL-6) and IL-10 after transplantation rose evidently (p<0.01), while that of transforming growth factor-${beta}$ (TGF-${beta}$) was decreased (p<0.01). There was no statistically significant difference level of interferon-${\gamma}$ (IFN-${\gamma}$) (p>0.05). The incidence of IFI was 19.2% (9/47), and multivariate logistic regression revealed that IFI might be related to Th17 cell count (p<0.05), instead of Th1, Th2 and Treg cell counts as well as IL-6, IL-10, TGF-${beta}$ and IFN-${\gamma}$ levels (p>0.05). Conclusions: After Allo-HSCT, the immune reconstitution of $CD4^+T$ cells is delayed and Th17 cell count decreases obviously, which may be related to occurrence of IFI.

• 대한영양사협회학술지
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• 제15권2호
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• pp.168-178
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• 2009

Hematopoietic stem cell tranntation is being widely used in an attempt to treat many hematological diseases such as leukemia, anemia, and lymphoma. To evaluate the success of hematopoietic stem cell transplantation, it is very important to determine how rapidly engraftment occurs. Therefore, this retrospective study was conducted to determine which factors affected the term of engraftment during hematopoietic stem cell transplantation, while focusing on the oral intake status. To accomplish this, 416 patients who underwent transplant operations at St. Mary's hospital from May 2006 to April 2008 were evaluated. The long-term engraftment group was characterized as having longer fasting days and more frequent vomiting, diarrhea, and oral mucositis incidences than the short-term engraftment group. In addition, the inhibitors of oral intake such as vomiting, diarrhea, and oral mucositis developed frequently between the pre-transplantation and 2 weeks after transplantation. A significantly negative correlation was observed between the oral intake volume and the duration of the oral intake inhibitors. A multiple regression analysis revealed that the frequency of vomiting and oral mucositis during hematopoietic stem cell transplantation, the length of hospitalization, and the hematocrit level in the 2 weeks after hematopoietic stem cell transplantation were significant predictors of engraftment. The results of this study could be used to establish a guideline for nutritional assessment, nutritional goals, and nutritional support for patients during hematopoietic stem cell transplantation.

• BMB Reports
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• 제57권8호
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• pp.352-362
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• 2024

Hematopoietic stem cell transplantation (HSCT) remains an indispensable therapeutic strategy for various hematological diseases. This review discusses the pivotal role of bone marrow (BM) niches in influencing the efficacy of HSCT and evaluates the current animal models, emphasizing their limitations and the need for alternative models. Traditional animal models, mainly murine xenograft, have provided significant insights, but due to species-specific differences, are often constrained from accurately mimicking human physiological responses. These limitations highlight the importance of developing alternative models that can more realistically replicate human hematopoiesis. Emerging models that include BM organoids and BM-on-a-chip microfluidic systems promise enhanced understanding of HSCT dynamics. These models aim to provide more accurate simulations of the human BM microenvironment, potentially leading to improved preclinical assessments and therapeutic outcomes. This review highlights the complexities of the BM niche, discusses the limitations of current models, and suggests directions for future research using advanced model systems.

• 대한임상검사과학회지
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• 제38권1호
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• pp.9-15
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• 2006

Peripheral bood stem cell collection (PBSCC), including peripheral blood stem cell transplantation (PBSCT), has been utilized worldwide as a very beneficial treatment method instead of allogenic Bone Marrow Transplantation (BMT) because it has many advantages such as rapid bone marrow engraftment and hematopoietic recovery, easy and safe accessibility and lower risk of rejection compared with allogenic BMT. In order to identify most the observable parameter in PBSCC, we analyzed various hematological parameters before and after PBSCC, and evaluated the correlation between the time of bone marrow engraftment and the number of CD34+ cells. Thirteen patients, who underwent 54 PBSCCs from January, 2003 to August, 2004 at Chungnam National University Hospital due to various systemic neoplasms, were analyzed in aspects of various hematological parameters including CD34+ cells using by Flow Cytometry (FCM). PBSCC harvests are described below: Mononuclear cells (MNC) $2.3{\pm}1.4{\times}10^8/kg$ and CD34+ cells $0.63{\pm}0.35{\times}10^6/kg$ on average, respectively. There was a statistical significance in Hb and Hct before and after PBSCC, but not in WBC and platelet counts. The period to reach the hematological bone marrow engraftment was 13.4(10~21) days and 19.5(11~38) days according to the criteria of absolute neutrophile counts (ANC) ${\geq}500/uL$ and platelet counts ${\geq}50,000/{\mu}L$ in peripheral blood, respectively. There was a significant correlation between the numbers of CD34+ cell and ANC (p<0.05), and a borderline significance between MNC and ANC (p=0.051). We found that a group of patients, who were infused with CD34+ cells more than $3.5{\times}10^6/kg$, reached more rapidly the period of bone marrow engraftment in platelet counts (p=0.040). This present study suggested that Hb and Hct were the most useful parameters and should be closely monitored before and after PBSCC, that a PBSCT with the dosage of more than $3.5{\times}10^6/kg$ of CD34+ cells was needed to perform successful bone marrow engraftment, and additionally that platelet counts could be more useful in indicating bone marrow engraftment than ANC.

• 대한의생명과학회지
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• 제18권2호
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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.

• 생물치료정신의학
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• 제24권3호
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• pp.142-155
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• 2018

Insomnia in patients with hematopoietic stem cell transplantation(HSCT) has been underdiagnosed and undertreated. This study reviewed the frequency, characteristics, physical and psychological effects, and treatments of insomnia in HSCT patients to highlight clinical importance in this specialized population. Furthermore, the authors intended to suggest a model that would conceptualize insomnia in the context of HSCT. In the pre-transplant period, about half of patients with HSCT suffered from sleep disturbance. A substantial number of patients experienced distressing insomnia during the HSCT procedure and recovered to the level of the pre-transplant period. However, sleep disruption could be a chronic symptom in HSCT survivors and could negatively impact quality of control, cancer-related fatigue(CRF), immune function, and psychological distress. The 3P's model(Predisposing, Precipitating, Perpetuating) explains insomnia in cancer population and could be also relevant to HSCT patients with specific consideration of CRF, graft-versus-host diseases, specific properties of hematological disease, and protective isolated milieu. Effective treatment of insomnia in HSCT includes non-pharmacological(e.g., cognitive behavioral therapy, environmental modification) and pharmacological interventions. The decision of pharmacological treatment should be based on the issue of safety due to high risk of potential drug-drug interactions. Screening, treatment, and further research of insomnia in HSCT patients using validated subjective and/or objective measures are warranted.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7415-7419
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• 2013

The diagnosis of latent Mycobacterium tuberculosis infection (LTBI) is recommended in hematological malignancy patients and before hematopoietic stem cell transplantation (Guidelines for the prevention and management of infectious complications of solid organ transplantation, 2004). Compared to traditional methods such as tuberculin skin test (TST), T-SPOT.TB has been shown to be more specific. In the present study we enrolled 536 patients for whom T-SPOT.TB was performed, among which 295 patients also received the TST test. The agreement (79%) between T-SPOT.TB and TST was poor (x=0.274, P<0.001). The patients with positive T-SPOT.TB results numbered 62 (11.6%), in which only 20 (48.8%) of the 41 receiving the TST test had positive results. A majority of the patients with T-SPOT.TB positive results had some other evidence ofTB, such as TB history, clinical symptoms and an abnormal chest CT scan. Active TB was found in 9 patients, in which 2 had negative TST results. We followed up the patients and no one developed active TB. Our study suggested that the T-SPOT.TB may be more useful for screening LTBI and active TB in hematological malignancy patients and hematopoietic stem cell transplant recipients than the TST test.

• 한국융합학회논문지
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• 제8권4호
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• pp.49-57
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• 2017

본 연구는 소아암 환아의 조혈모세포이식 후 성장을 확인하고, 이에 영향을 미치는 요인들을 조사하고자 진행된 융합연구이다. 2009년 2월부터 3월까지 조혈모세포이식을 받은 소아암 환아 112명의 의무기록으로부터 키와 몸무게를 조사하였으며 자료 분석을 위해 혼합효과 모델을 사용하였다. 연구 결과 조혈모세포이식 후 대상자의 신장과 체중의 표준과의 평균표준편차값이 음의 값이었으며 동종이식 보다 자가이식의 경우 신장(p=0.0008)과 체중(p=0.0012)의 평균이 낮았다. 이식 후 신장에 영향을 주는 것으로 대상자의 이식 시 연령(p=0.0251)과 이식 형태(p=0.0020)가 확인되었으며. 동종이식 환아에서는 성장에 영향을 주는 것으로 스테로이드의 사용량이 확인되었다(p=0.0403). 대상자의 이식 후 체중은 이식 시 연령(p=0.0042), 이식형태(p=0.0035) 그리고 총정맥영양의 주입기간(p=0.0159)에 영향을 받는 것으로 나타났다. 본 연구 결과를 바탕으로 소아암 환아의 조혈모세포이식 후 성장이 잘 이루어질 수 있도록 성장저하의 고위험군을 식별할 수 있도록 하여야하며, 이러한 환아에게 적절한 간호중재가 수행되어야 할 것이다.

• The Korean journal of internal medicine
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• 제39권1호
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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.

• BMB Reports
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• 제56권9호
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• pp.482-487
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• 2023

Hematopoiesis is regulated by crosstalk between long-term repopulating hematopoietic stem cells (LT-HSCs) and supporting niche cells in the bone marrow (BM). Here, we describe the role of KAI1, which is mainly expressed on LT-HSCs and rarely on other hematopoietic stem-progenitor cells (HSPCs), in niche-mediated LT-HSC maintenance. KAI1 activates TGF-β1/Smad3 signal in LT-HSCs, leading to the induction of CDK inhibitors and inhibition of the cell cycle. The KAI1-binding partner DARC is expressed on macrophages and stabilizes KAI1 on LT-HSCs, promoting their quiescence. Conversely, when DARC+ BM macrophages were absent, the level of surface KAI1 on LT-HSCs decreases, leading to cell-cycle entry, proliferation, and differentiation. Thus, KAI1 acts as a functional surface marker of LT-HSCs that regulates dormancy through interaction with DARC-expressing macrophages in the BM stem cell niche. Recently, we showed very special and rare macrophages expressing α-SMA+ COX2+ & DARC+ induce not only dormancy of LT-HSC through interaction of KAI1-DARC but also protect HSCs by down-regulating ROS through COX2 signaling. In the near future, the strategy to combine KAI1-positive LT-HSCs and α-SMA/Cox2/DARC triple-positive macrophages will improve the efficacy of stem cell transplantation after the ablative chemo-therapy for hematological disorders including leukemia.