Hyo Jae Kang

Effect of iron overload and iron-chelating therapy on allogeneic hematopoietic SCT in children.

Iron overload is known to increase complications of hematopoietic SCT (HSCT). We investigated the association of pre-transplant ferritin level with complications and survival after allogeneic HSCT, and evaluated the efficacy of iron-chelating therapy before HSCT. We retrospectively reviewed 101 patients who underwent allogeneic HSCT and divided these patients into three groups: F>1000, patients with ferritin level above 1000 ng/ml at the time of HSCT; F<1000, patients whose ferritin levels were maintained below 1000 ng/ml before HSCT without iron-chelating therapy; IC, patients with ferritin level decreased to less than 1000 ng/ml after iron-chelating therapy before HSCT. In the comparison between the F>1000 group and the F<1000 group, hyperbilirubinemia and treatment-related mortality (TRM) were significantly higher in the F>1000 group. The F>1000 group also showed decreased OS and EFS. In the comparison of the F<1000 and IC groups, there was no significant difference in complications and survival. When compared with the F>1000 group, the IC group showed lower TRM and higher survival. Elevated serum ferritin level was associated with increased TRM and decreased survival, and the analysis of the IC group suggested the benefit of iron-chelating therapy to improve the outcome of HSCT.

EBUS-centred versus EUS-centred mediastinal staging in lung cancer: a randomised controlled trial

Background The impact of procedure sequence and primary procedure has not been studied in the combined application of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in lung cancer staging. Methods In a randomised controlled trial, 160 patients with histologically confirmed or strongly suspected potentially operable non-small cell lung cancer were enrolled (Group A, n=80, EBUS-centred; Group B, n=80, EUS-centred). EBUS-TBNA and EUS-FNA with an ultrasound bronchoscope were used as the first procedures in Groups A and B, respectively, and secondary procedures (EUS-FNA in Group A, EBUS-TBNA in Group B) were added. Results Diagnostic values were evaluated in 148 patients (74 in each group). In Groups A and B the diagnostic accuracy (93.2% (95% CI 87.5% to 99.0%) vs 97.3% (95% CI 93.6% to 101.0%), p=0.245) and sensitivity (85.3% (95% CI 68.9% to 95.0%) vs 92.0% (95% CI 74.0% to 99.0%), p=0.431) in detecting mediastinal metastasis were not statistically different. In Group A, adding EUS-FNA to EBUS-TBNA did not significantly increase the accuracy (from 91.9% to 93.2%, p=0.754) or sensitivity (from 82.4% to 85.3%, p=0.742). In group B, adding EBUS-TBNA to EUS-FNA increased the accuracy (from 86.5% to 97.3%, p=0.016) and sensitivity (from 60.0% to 92.0%, p=0.008). There were no intergroup differences in procedure time, cardiorespiratory parameters during procedures, complications or patient satisfaction. Conclusions Using a combination of EBUS-TBNA and EUS-FNA in mediastinal staging, we found that diagnostic values and patient satisfaction were not different between the EBUS-centred and EUS-centred groups. However, the necessity for EBUS-TBNA following EUS suggests that EBUS-TBNA is a better primary procedure in endoscopic mediastinal staging of potentially operable lung cancer. Trial Registration number ClinicalTrials.gov number NCT01385111.

Hepatic veno-occlusive disease in children after hematopoietic stem cell transplantation: incidence, risk factors, and outcome

Four hundred and sixty-seven hematopoietic stem cell transplantations (HSCTs) (217 autologous and 250 allogeneic HSCT) were performed in 374 children at four pediatric HSCT centers in Korea from January 2005 to December 2007. Among 467 transplants, veno-occlusive disease (VOD) developed in 72 transplants (15.4%) at a median of 10 days after HSCT. Multivariate analysis showed that BU or TBI-containing regimen (P=0.002), VOD prophylaxis without lipo-prostaglandin E1 (PGE1) (P=0.012), number of previous HSCT (P=0.014), and pretransplant serum ferritin (P=0.018) were independent risk factors for developing VOD. Mean serum ferritin levels were significantly higher in HSCT with VOD (2109.6±2842.5 ng/ml) than in HSCT without VOD (1315.9±1094.4 ng/ml) (P<0.001). The relative risk of death within 100 days of HSCT in transplants with VOD compared with transplants without VOD was 3.39 (confidence interval: 1.78–6.45). Our results suggest that lipo-PGE1 might have a protective effect against the development of VOD, and pretransplant serum ferritin could act as a risk factor for VOD. A larger prospective study is needed to confirm a possible role of lipo-PGE1 and iron chelation therapy in reducing the incidence of VOD.

Fludarabine, cyclophosphamide plus thymoglobulin conditioning regimen for unrelated bone marrow transplantation in severe aplastic anemia.

Summary:Antithymocyte globulin (ATG) has been used in severe aplastic anemia (SAA) as a part of the conditioning regimen. Among the many kinds of ATG preparations, thymoglobulin had been found to be more effective in preventing GVHD and rejection of organ transplants. As the fludarabine-based conditioning regimens without total body irradiation have been reported to be promising for bone marrow transplantation (BMT) from alternative donors in SAA, thymoglobulin was added to fludarabine and cyclophosphamide conditioning to reduce GVHD and to allow good engraftment in unrelated BMT. Five patients underwent BMT with cyclophosphamide (50 mg/kg once daily i.v. on days −9, −8, −7 and −6), fludarabine (30 mg/m2 once daily i.v. on days −5, −4, −3 and −2) and thymoglobulin (2.5 mg/kg once daily i.v. on days −3, −2 and −1) from HLA-matched unrelated donors. Complete donor type hematologic recovery was achieved in all patients. No serious complication occurred during BMT. Only one patient developed grade I acute GVHD resolved spontaneously. Except for one who had rupture of hepatic adenoma 78 days after BMT, all the other four patients are still alive with median 566 days. Fludarabine, cyclophosphamide plus thymoglobulin conditioning allows for the promising results of good engraftment, tolerable toxicity and minimal GVHD.

Early engraftment kinetics of two units cord blood transplantation.

Cord blood transplantation (CBT) is a promising alternative means of allogeneic stem cell transplantation. However, limited cell doses may compromise outcome. To enhance engraftment, CBT has been conducted using two units with promising results. However, little is known about the mechanism of engraftment. Here, we analyzed the early engraftment kinetics of eight patients given two unit umbilical CBT. Early engraftment kinetics revealed dominancy of one of two units from the day of engraftment (absolute neutrophil count >0.5 × 109/l). The median value of percentage of the predominant unit by chimerism analysis at the time of engraftment was 88% (60–100%). Two units CBT was found to be a safe, effective and promising alternative treatment option with good engraftment potential. Dominancy occurred early after CBT and is probably influenced by multiple factors.

Autologous peripheral blood stem cell transplantation with BCVAC conditioning in childhood acute myeloid leukemia.

Summary:Autologous peripheral blood stem cell transplantation (APBSCT) after intensifying conditioning is one of the post-remission therapeutic options in childhood acute myeloid leukemia (AML) patients without a matched family donor, but the optimal conditioning regimen has not been defined. This study was performed to evaluate the efficacy of a novel conditioning regimen without busulfan or total body irradiation. In total, 28 children with AML underwent APBSCT with BCVAC (BCNU, etoposide, cytosine arabinoside and cyclophosphamide) conditioning regimen during first remission. The event-free survival rate was 71.43% for all patients and the only cause of treatment failure was relapse. Eight male patients recurred at 1–11 months (median 5 months) after APBSCT. One patient remains alive with salvage therapy after relapse. With the exception of fever, mucositis and diarrhea, no serious complications occurred during APBSCT, including veno-occlusive disease (VOD), and there was no transplantation-related mortality. One patient developed secondary MDS after APBSCT but recovered hematologically on medication. APBSCT with BCVAC conditioning was found to be a safe and effective alternative option for patients with childhood AML in first remission, without a matched family donor.

Vitamin D deficiency and changes in serum vitamin D levels with treatment among tuberculosis patients in South Korea

Background and objective:  Vitamin D deficiency has been reported to be associated with the development of active tuberculosis (TB), but many discrepancies exist among studies. The aims of this study were to compare the frequency of vitamin D deficiency in a Korean population of TB patients and control subjects, and to monitor the changes in vitamin D levels during TB treatment.

Adverse pulmonary reactions associated with the use of monoclonal antibodies in cancer patients.

BACKGROUND The incidence and clinical characteristics of adverse pulmonary reactions resulting from anticancer monoclonal antibody (mAbs) therapy have not been well described. We determined the incidence and clinical characteristics of adverse pulmonary reactions in patients treated with anticancer chemotherapy including mAbs. METHODS A retrospective cohort study was performed including patients who were treated with a chemotherapeutic regimen that included rituximab, trastuzumab, cetuximab, or bevacizumab at Seoul National University Hospital between January 1, 2004 and December 31, 2008. Rates of adverse pulmonary reactions classified as non-infectious and infectious complications were compared with those among patients treated with comparable regimens without mAbs. RESULTS In total, 1078 patients were included (418 for rituximab, 329 for trastuzumab, 122 for cetuximab, 209 for bevacizumab). Adverse pulmonary reactions were identified in 36 patients (3.5%) and the incidence differed among agents: cetuximab (9%), rituximab (5.3%), trastuzumab (0.6%), bevacizumab (0.5%). Infectious pulmonary complications occurred in 28 patients, and eight patients experienced non-infectious pulmonary complications, most commonly interstitial lung disease (6 patients). In a multivariate analysis, low serum albumin level was associated with the development of pulmonary complications. The incidence of overall adverse pulmonary reactions did not differ between the mAbs users and the 1012 patients treated with comparable regimens other than mAbs (3.5% vs. 2.8%, P=0.53). CONCLUSIONS Infectious and non-infectious adverse pulmonary reactions occur in patients with cancer who are administered a regimen including mAbs. Clinicians should be alert for the possibility of pulmonary adverse reactions, particularly among patients with low serum albumin levels.

Successful first-line treatment with double umbilical cord blood transplantation in severe aplastic anemia

Successful first-line treatment with double umbilical cord blood transplantation in severe aplastic anemia

Technical Aspects of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is becoming a standard method for invasive mediastinal staging and for the diagnosis of paratracheal and peribronchial lesions. It is essential to understand the technical aspects of EBUS-TBNA to ensure safe and efficient procedures. In this review, we discuss the practical aspects to be considered during EBUS-TBNA, including anesthesia, manipulation of equipment, understanding mediastinal ultrasound images, target selection, number of aspirations needed per target, sample handling, and complications.