강형진 교수

X-linked chronic granulomatous disease (CGD) is an inherited immunodeficiency caused by a defect in the gp91phox gene. In an effort to treat X-CGD, we investigated the safety and efficacy of gene therapy using a retroviral vector, MT-gp91. Two X-CGD patients received autologous CD34+ cells transduced with MT-gp91 after a conditioning regimen consisting of fludarabine and busulfan. The level of gene-marked cells was highest at day 21 (8.3 and 11.7% in peripheral blood cells) but decreased to 0.08

Antithymocyte globulin (ATG) has been used in severe aplastic anemia (SAA) as part of the conditioning regimen. Among the many kinds of ATG preparations, thymoglobulin had been found to be more effective for preventing graft-versus-host disease (GVHD) and the rejection of organ transplants. After the promising results of our preliminary study, we conducted a phase II prospective multicenter clinical trial using a fludarabine (Flu), cyclophosphamide (Cy), and thymoglobulin conditioning regimen to

Genetic polymorphisms are important factors in the effects and toxicity of chemotherapeutics. To analyze the pharmacogenetic and ethnic differences in chemotherapeutics, major genes implicated in the treatment of acute lymphoblastic leukemia (ALL) were analyzed. Eighteen loci of 16 genes in 100 patients with ALL were analyzed. The distribution of variant alleles were CYP3A4*1B (0%), CYP3A5*3 (0%), GSTM1 (21%), GSTP1 (21%), GSTT1 (16%), MDR1 exon 21 (77%), MDR1 exon 26 (61%), MTHFR 677 (63%), MTH

Conditioning regimens for pediatric acute lymphoblastic leukemia (ALL) usually include total body irradiation (TBI), but TBI may result in serious sequelae. Busulfan and cyclophosphamide have been used as an alternative to TBI. Etoposide also has been widely used to enhance antileukemic effect. However, toxicities have been reported in some studies using busulfan, cyclophosphamide, and etoposide regimen. A reduced toxicity myeloablative regimen using busulfan and fludarabine showed promising res

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with post-transplantation cyclophosphamide (PTCy) was performed previously in adults using a nonmyeloablative conditioning regimen and bone marrow as a graft source. In an effort to reduce relapse rates, myeloablative conditioning regimens with higher intensities are now used. We used an intensive daily pharmacokinetic monitoring method for busulfan dosing in children for effective myeloablation and to reduce toxicity. Here, we

BACKGROUND: This study evaluated the effect of radiation dose rate in patients with hematolymphoid malignancies undergoing myeloablative conditioning with total body irradiation (TBI), for hematopoietic stem cell transplantation. METHODS: The incidence of pulmonary toxicity (PT) and treatment efficacy were compared between the conventional (≥ 6 cGy/min) and reduced dose rate (< 6 cGy/min). Seventy-seven patients receiving once-daily TBI between 2000 and 2016 were reviewed. We compared the cumula

Owing to its narrow therapeutic range and high pharmacokinetic variability, optimal dosing for busulfan is important to minimise overexposure-related systemic toxicity and underexposure-related graft failure. Using global metabolomics, we investigated biomarkers for predicting busulfan exposure. We analysed urine samples obtained before busulfan administration from 59 paediatric patients divided into 3 groups classified by area under the busulfan concentration-time curve (AUC), i.e., low-, mediu

Transfusion-associated iron overload induces systemic toxicity. Deferasirox, a convenient long acting oral agent, has recently been introduced in clinical practice with a promising efficacy. But there are some patients who experience drug-related toxicities and cannot tolerate it. To investigate effect of genetic variations on the toxicities and find optimal target population, we analyzed the genetic polymorphisms of UDP-glucuronosyltransferase 1A (UGT1A) subfamily, multi-drug resistance-associa

Busulfan, a bifunctional alkylating agent, has been used as a conditioning regimen prior to allogeneic hematopoietic stem cell transplantation (HSCT). The aim of this study was to derive a novel once-daily intravenous (IV) busulfan dosing nomogram for pediatric patients undergoing HSCT using a population pharmacokinetic (PK) model. A population PK analysis was performed using 2183 busulfan concentrations in 137 pediatric patients (age: 0.6-22.2 years), who received IV busulfan once-daily for 4 d

Malignant peripheral nerve sheath tumors are rare tumors that originate from Schwann cells. Patients with neurofibromatosis type 1 are prone to develop these tumors. Due to their rarity and lack of established treatment, the prognosis of malignant peripheral nerve sheath tumors is poor. A retrospective study was conducted on children treated for malignant peripheral nerve sheath tumors at the Seoul National University Children's Hospital between 2007 and 2016. Eleven patients were diagnosed with

Endothelial progenitor cells (EPCs) were recently demonstrated to exist in human cord blood. Phytohaemagglutinin (PHA), a potent mitogen for mononuclear cells was used to induce EPCs from unsorted cord blood mononuclear cells (CBMCs). Adherent cells in clusters appeared approximately 24 h after CBMCs were cultured in plain Roswell Park Memorial Institute media containing 10% fetal bovine serum (culture media) and PHA. Adherent cells were further propagated for 1 week in plain culture media. Flow