• 한국임상약학회지
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• 제20권3호
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• pp.193-199
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• 2010

Tacrolimus, an immunosuppressant prescribed against graft-versus-host disease (GVHD) in patients with allogeneichematopoietic stem cell transplantation (HSCT), is affected to change its pharmacokinetic properties by various factors. For this reason, it is needed a close monitoring to adjust dosage amount in order to optimize the blood concentration of tacrolimus is located within the effective range. According to our in-house study, 62% of HSCT-patients were needed dosage-adjustment and it is necessary to optimize the current immunosuppressive regimen in clinical settings. A retrospective study was designed to evaluate the dosing regimen (converting ratio of IV:PO=1:4) of tacrolimus in HSCT patients (n=62). After collecting data from patient's profile and medical record, pharmacokinetic parameters were calculate and compared between the estimated and the actual values in the selected subjects (n=58). It was found that the bioavailabilty (BA) of oral tacrolimus was 40.5% very much different from that is known as 25%. It implies that the current protocol has a potent risk causes dose-related toxicities to the patients. Furthermore, analyses among factors demonstrated that there was no statistical significance between BA of tacrolimus and the variable factors. In the clinical perspectives, the current converting ratio of tacrolimus in patients with HSCT to be re-considered and an appropriate and optimal alternative regimen should be adopted to prevent GVHD and to increase the quality of life of patients.

• 한국임상약학회지
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• 제28권1호
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• pp.24-29
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• 2018

Background: Cyclosporine is an immunosuppressive agent used to treat and prevent graft versus host reaction (GVHR)-a complication associated with stem cell transplantation. This study aimed to develop a population pharmacokinetic model of cyclosporine and investigate factors affecting cyclosporine clearance in pediatric hematopoietic stem cell transplant patients. Methods: A total of 650 cyclosporine concentrations recorded in 65 patients who underwent hematopoietic stem cell transplantation were used. Data including age, sex, weight, height, body surface area (BSA), type of disease, chemotherapy before stem cell transplantation, type of donor, serum creatinine levels, total bilirubin concentration, hematocrit value, and type of concomitant anti-fungal agents and methylprednisolone used were retrospectively collected. Data related to cyclosporine dosage, administration time, and blood concentration were also collected. All data were analyzed using the non-linear mixed effect model; a two-compartment model with first-order elimination was used. Results: The population pharmacokinetic model of cyclosporine using the NONMEM program was as follows: $CL(L/h)=5.9{\times}(BSA/1.2)^{0.9}$, V2 (L) = 54.5, Q (L/h) = 3.5, V3 (L) = 1080.0, $k_a(h^{-1})=0.000377$. BSA was selected as a covariate of cyclosporine clearance, which increased with an increase in BSA. Conclusion: A population pharmacokinetic model for Korean pediatric hematopoietic stem cell transplant patients was developed, and the important factor affecting cyclosporine clearance was found to be BSA. The model might contribute to the development of the most appropriate dosing regimen for cyclosporine. Further studies on population pharmacokinetics should be carried out, prospectively targeting pediatric patients.

• 한국임상약학회지
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• 제28권3호
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• pp.224-229
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• 2018

Background: The patients receiving hematopoietic stem cell transplantation (HSCT) are known to have a high incidence of breakthrough nausea and vomiting due to the conditioning regimen. The purpose of this study was to evaluate the adequacy of antiemetic therapy for breakthrough nausea and vomiting in patients receiving HSCT and to propose an effective treatment regimen. Methods: We retrospectively reviewed the electronic medical records of 109 adult patients. The collected data were used to identify (1) antiemetic and dosing regimens prescribed for controlling breakthrough nausea and vomiting, (2) the rate of patients who developed breakthrough nausea and vomiting, and (3) the percent of antiemetics prescribed on the day of symptom onset. Based on the National Comprehensive Cancer Network guideline, we assessed the suitability of antiemetics for breakthrough nausea and vomiting, and prescription timing. Results: All patients were prescribed pro re nata antiemetics. About 40.0%, 41.4%, and 18.6% of patients were using one, two, and three or more additional drugs for breakthrough nausea and vomiting, respectively. The most frequently administered drugs were intravenous metoclopramide (43.8%) and granisetron patch (36.2%). Breakthrough nausea and vomiting occurred in 87 patients (79.1%) and they developed symptoms 320 cases. About 220 cases (68.8%) were treated with additional antiemetics on the day of symptom onset and the rate of symptom resolution was only 10.3% (9 patients). Conclusion: The breakthrough nausea and vomiting in patients receiving HSCT occurred very frequently and was hard to control, thus requiring more rapid and aggressive treatments.

• Tuberculosis and Respiratory Diseases
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• 제47권1호
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• pp.77-89
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• 1999

연구 배경: 고위험군의 악성 질환의 치료로 최근에 시도되고 있는 고용량 항암화학요법은 기존의 치료보다 치료 반응율이 높고 생존의 향상을 기대할수 있는 방법이다. 그러나 치료와 관련된 부작용도 있어 이환율 및 사망률도 높다. 말초 조혈모세포이식을 이용한 고용량 항암화학요법 후에 발생하는 특발성 폐렴 증후군은 감염성 원인을 배제한다면 약제에 의한 폐독성으로 유발되었을 가능성이 가장 높다. 저자들은 약제 독성으로 유발되었을 것으로 추정되는 폐렴 증후군에 대하여 알아보고자 하였다. 방법: 1995년 5월부터 1997년 12월까지 아주대학교병원에서 말초 조혈모세포이식을 이용한 고용량 항암화학 요법을 시행받은 환자들을 대상으로 하였다. 이들 중 특발성 폐렴 증후군이 발생한 5례에서 경기관지폐생검을 시행하고 그 임상 양상과 치료 결과를 후향적으로 분석하였다. 결과: 전체 대상 환자는 97례이었으며 이들중 5례(5.1%)에서 특발성 폐렴 증후군이 발생하였다. 5례의 환자의 연령은 평균 $41{\pm}13$세, 남녀비는 3:2였으며 유방암 3례, 악성 림프종 2례이었다. 사용된 항암제는 CBP regimen 3례, BEAC regimen 1례, BEAM regimen 1례이었으며, 사용된 용량은 BCNU 300-400 mg/$m^2$, cyclophosphsmide 6,000 mg/$m^2$이었다. 다섯 례 모두에서 고용량 항암화학요법 전에 방사선 치료를 받았다. 고용량 항암화학요법을 시행한지 평균 14주 후 (4-26주)에 기침, 호흡곤란, 발열 등을 동반한 폐침윤이 발생하였다. 흉부 방사선 검사 소견상 3례에서는 양측성, 2례에서는 우하엽에 국한된 미만성의 폐침윤을 보였다. 경기관지폐생검 결과 폐포 손상과 격막의 비후, 비정상적인 제 II 형 폐세포의 증식이 관찰되었고 악성 세포의 침윤이나 감염성 질환 등의 소견은 없었다. 모든 환자에서 스테로이드를 투여하였으나 2례에서는 급성 호흡부전증으로 진행하여 사망하였다. 3례에서는 폐병변이 소실되고 중상도 호전되었으나 1례는 확장성 심근병으로 사망하였고 2례는 호전되어 폐병변이 없는 상태에서 외래 관찰 중이다. 결론: 말초 조혈모세포이식을 이용한 고용량 항암화학요법은 치료 효과가 기존의 항암치료보다 높지만 BCNU를 포함하는 복합 화학요법을 사용하는 경우 약제에 폐손상이 발생할 가능성이 있어 적절한 환자의 선정과 폐손상을 최소화할 수 있도록 유의하여야 한다.

• 종양간호연구
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• 제1권1호
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• pp.5-17
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• 2001

It is known that aggressive treatment of chemotherapy, radiation and autogenous stem cell transplantation is effective for prevention of recurrence in the high-risk breast cancer patients. It was assumed that this procedure takes a longer time and decreases the quality of life more than the standard adjuvant chemotherapy. However, there are few studies comparing the quality of life of patients having bone marrow transplantation and adjuvant chemotherapy. Most of the studies were focused on the quality of life in one point of time, such as only during the early treatment stage, only overall quality of life rather than specific dimensions of the quality of life. The purposes of this study are 1) to identify the difference of the quality of life between two different treatment patterns, adjuvant chemotherapy and autogenous stem cell transplantation: 2) to identify the mostly affected dimension and the periods of time affected by the treatment patterns; and 3) to identify the trajectories of quality of life in each treatment pattern. This is a time series design that measures 4 different points of times. At the beginning of the study, 19 patients were placed in the chemotherapy group and 12 in the group of auto-peripheral blood stem cell transplantation. The inclusion criterion was the advanced disease stage of 3 or over with metastasis of more than 5 lymph nodes. The exclusion criteria were 1) anyone who has metastasis to other organ; 2) anyone who had psychological problems. Ferrell's Quality of Life Scale for Cancer Survivors 41 items on a 10 point scale was used. The QOL-CS includes 4 dimensions, which were labeled physical, psychological, social, and spiritual. The Cronbach‘s alpha of this scale was 0.89. Mann-Whitney U test and Friedman test were used to test each hypothesis. In comparison of the two groups, the quality of life of the bone marrow transplantation group dramatically increased at the 3rd and 6th month after transplantation, while the chemotherapy groups results stayed lower. The most affected dimension of the quality of life at the end of the treatment was the physical dimension. However, it and increased along with time, while the psychological dimension values remained low over the long-term period. Intensive nursing care is needed during the entire period of chemotherapy in all patients having chemotherapy, and is also required for right after cases of bone marrow transplantation.

• Tuberculosis and Respiratory Diseases
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• 제71권6호
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• pp.459-463
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• 2011

Pulmonary complications occur in 40~60% of patients who receive hematopoietic stem cell transplantation (HSCT) and are a source of substantial morbidity and mortality. Acute eosinophilic pneumonia (AEP) is an uncommon, non-infectious pulmonary complication occurring in HSCT recipients. We now report the case of a 52-year-old man with AEP who was treated with allogenic HSCT due to acute myeloid leukemia. He complained of fever, cough and dyspnea 390 days after allogenic HSCT. He also had skin and hepatic graft versus host disease (GVHD). Hypoxemia, diffuse pulmonary infiltrates on a chest x-ray and eosinophilia in bronchoalveolar lavage fluid were also noted in several tests. His symptoms, pulmonary infiltrates, hepatic dysfunction and skin lesions rapidly improved after treatment with corticosteroid therapy. Our case supports the idea that AEP is a late phase non-infectious pulmonary complication and one of the manifestations of chronic GVHD.

• 한국보건간호학회지
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• 제14권2호
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• pp.191-202
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• 2000

This study was conducted for 39 patients who are recipients of allogeneic hemopoietic stem cell transplantation at BMT ward of St. Mary's hospital affiliated to Catholic University of Korea from April to September 1999. The subjects were devided into two groups; those who received both TEl and chemo therapy as conditioning regimen (TEl group). and those who used chemo agents as singular conditioning regimen (chemo group). The oral intake status of the two groups were compared through physical assessment and blood chemistry exam of the subjects, and factors influencing their nutritional change and oral intake were explored in each stage of the transplantation (six stages: admission, conditional stage, date of transplantation, one week after transplantation, two weeks after transplantation, and three weeks after transplantation). The prior aim of the study was to provide baseline data to minimize delayed treatment from nutritional deficiency of the subjects. The results were as follows: 1. TBI group was significantly decreased of oral calorie intake in two weeks after transplantation compared to admission and conditioning stage while that of chemo group was significantly decreased on the date of transplantation. 2. TBI group was significantly decreased of protein intake in two weeks after transplantation compared to admission and conditioning stage. In chemo group, protein intake was significantly decreased on the date of transplantation compared to admission. It was remarkable that TBI group showed lesser protein intake than chemo group. 3. Both group were significantly decreased of BMI in one week and three weeks after transplantation compared to admission. TBI group showed significantly higher BMI than chemo group. 4. Both group were significantly decreased of Triceps Skinfold Thickness (TST)on the date of transplantation compared to admission stage. 5. TBI group was significantly decreased of mid-arm muscle circumference (MAMC) in two weeks after transplantation compared to admission, conditioning, date of transplantation. 6. TBI group was significantly decreased of albumin level in two weeks after transplantation compared admission stage. In chemo group, it was significantly decreased on the date of transplantation compared to admission, three weeks after the transplantation. 7. TBI group was significantly decreased of transferrin level in two weeks after transplantation compared admission, conditioning, date of transplantation and one week after transplantation. In chemo group, it was decreased of transferrin level in 3 weeks after transplantation. 8. Oral intake of TEl group was impacted by vomiting before transplantation and gingivitis after transplantation. In chemo group, it was impacted by vomiting before transplantation and by two factors, gingivitis and nausea, after transplantation. The results showed oral calorie intake was not different between the two groups while protein intake was significantly lower in TBI group than chemo group. Oral intake was significantly impacted by vomiting before transplantation in both groups, but affected by oral gingivitis in TBI group and gingivitis and nausea in chemo group after transplantation. This findings present that standardized strategies to manage nutrition and gingivitis more effectively are desperately needed to enhance oral intake and protein intake of patients who receive TBI as conditioning regimen.

• Journal of Yeungnam Medical Science
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• 제29권2호
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• pp.96-101
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• 2012

Allogeneic hematopoietic stem cell transplantation (HSCT) is considered the optimal curative treatment for acute myeloid leukemia (AML), but some patients develop bone marrow relapse due to remnant leukemia, and few patients develop extramedullary relapse without bone marrow relapse. Isolated extramedullary relapse (IMER) is defined as extramedullary relapse without bone marrow relapse. IMER has been reported in various sites, including the skin, soft tissue, and central nervous system(CNS). Isolated CNS relapse is relatively rare and is associated with poor prognosis due to the absence of an optimal treatment for it. Reported herein is a case involving an adult AML woman who suffered from isolated extramedullary relapse in the CNS after allogeneic HSCT. She was treated with intrathecal chemotherapy and whole-brain and spine radiotherapy, followed by systemic chemotherapy. She is currently well, with no evidence of leukemia recurrence for over six years.

• 한국임상약학회지
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• 제12권1호
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• pp.7-12
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• 2002

Pharmacokinetic parameters and dosage of aminoglycosides (AGs) were studied retrospectively in 36 patients with neutropenic fever after stem cell transplantation in Seoul National University Hospital from July 1996 to June 2001. AGs pharmacokinetic parameters were calculated with steady-state peak and trough serum drug concentrations by the method of Sawchuk and Zaske et at. The calculated aminoglycosides volume of distribution and clearance were greater than population value $(0.36\pm0.06\;L/kg,\;116\pm32\;ml/min/1.73\;m^2,\;respectively)$. The average dosage of aminoglycosides required to maintain optimal serum AGs concentration was also greater than recommended dose in insert paper. The average dosage of amikacin was $11\pm2.1$ mg/kg every 12 hours (In case of tobramycin, $2.09\pm0.37$ mg/kg every 8 hours or $2.59\pm0.20$ mg/kg every 12 hours). The relationship between AGs volume of distribution and sex, serum albumin (g/dl), body mass index $(kg/m^2)$, body weight change $(\%)$, the amount of fluid inpu (ml/kg/day), the degree of hematocrit decrease $(\%)$ were studied respectively. Univariate anlysis revealed that body mass index $(kg/m^2)$, the amount of fluid input (ml/kg/day) and the degree of hematocrit decrease $(\%)$ had significant correlation with aminoglycosides volume of distribution. But sex, serum albumin, body weight change $(\%)$ had no significant correlation with aminoglycosides volume of distribution.

• 대한한방내과학회지
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• 제44권5호
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• pp.1092-1100
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• 2023

Introduction: We present a case of multiple myeloma with amyloidosis, which has features of peripheral neuropathy after induction chemotherapy before autologous peripheral blood stem cell transplantation, in a 56-year-old woman with Korean medicine. Case Presentation: For 17 days of hospitalization, the patient with complaints of numbness and a tingling sensation in the hands and feet was treated with acupuncture, herbal medicine. To reduce the symptoms, we provided Korean medicine treatments, including herbal medicine, acupuncture, and moxibustion. The Visual Analog Scale (VAS) was used to evaluate the results of the treatment. Until discharge, the VAS scores decreased for both hands and the foot tingling sensation. Conclusion: According to these results, Korean medicine treatment may be considered an effective treatment for tingling sensations in a patient with multiple myeloma with amyloidosis. Prospective studies are needed in the future to confirm and expand these findings.