Dong Hwan Kim

Interleukin-10 gene polymorphism influences the prognosis of T-cell non-Hodgkin lymphomas.

Interleukin‐10 (IL‐10) is one of the cytokines implicated in the pathogenesis of diffuse large B‐cell lymphoma (DLBCL) in which it acts as auto/paracrine growth factor for lymphoma growth. T‐cell non‐Hodgkin lymphoma (NHL) is a heterogeneous disease, the biological basis of which is not fully understood. Some evidence suggests that IL‐10 might be associated with the progression of T‐cell NHLs and that IL‐10 may be involved in a rescue effect, protecting T cells from apoptotic cell death associated with upregulated bcl‐2 expression. The current study evaluated the impact of IL‐10 gene (IL10) polymorphism on the response to chemotherapy and survival in T‐cell NHL. IL10 polymorphisms were determined in 108 patients with T‐cell NHL. The response to chemotherapy was not dependent on IL10 polymorphism, while survival differed significantly according to IL10 polymorphism. The group with ATA haplotype showed superior overall survival (61·2u2003±u20035·9% vs. 21·2u2003±u200311·7%, Pu2003=u20030·001) and failure‐free survival (35·0u2003±u20035·7% vs. 13·2u2003±u20038·7%, Pu2003=u20030·001) compared to those without ATA haplotype. The ATA haplotype was identified as a favourable prognostic factor compared to non‐ATA haplotype (Pu2003=u20030·037, hazard ratio 2·1), together with international prognostic index (IPI) in a multivariate model for overall survival. In conclusion, IL10 polymorphism may affect the survival of T‐cell NHL patients.

Trough plasma imatinib levels are correlated with optimal cytogenetic responses at 6 months after treatment with standard dose of imatinib in newly diagnosed chronic myeloid leukemia

To investigate the correlation of trough imatinib mesylate (IM) levels with cytogenetic or molecular responses, we measured trough IM levels in patients with chronic myeloid leukemia, chronic phase (CML-CP), at 6 months of treatment with a standard dose of IM. Eighty-seven newly diagnosed patients with CML-CP were prospectively enrolled. Seventy-eight patients (89.7%) showed an optimal response (complete or partial cytogenetic response) at 6 months. Trough IM levels were 1378u200a±u200a725 ng/mL. When categorized into two groups, there was a statistically significant difference in numbers of patients with optimal and suboptimal responses at 6 months (group withu200a<1000: 80.6% vs. 19.4%;u200a≥1000: 94.6% vs. 5.4%; pu200a=u200a0.032), and in numbers of patients with early major molecular response (early-MMR) and without MMR at 6 months (group withu200a<1000: 3.2% vs. 96.8%;u200a≥1000: 21.4% vs. 78.6%; pu200a=u200a0.047). In conclusion, the incidence of optimal cytogenetic response or early-MMR in patients with CML-CP treated with IM for 6 months was significantly higher in those with a trough level ofu200a≥1000 compared with those with a level ofu200a<1000. Dose escalation of IM can be one option in patients with CML showing suboptimal response or resistance to the standard dose of IM, especially with low trough plasma IM levels (<1000 ng/mL).

Vascular endothelial growth factor (VEGF) gene (VEGFA) polymorphism can predict the prognosis in acute myeloid leukaemia patients

Increased angiogenesis, mediated by vascular endothelial growth factor (VEGF), was associated with poor prognosis in acute myeloid leukaemia (AML) patients. The current study investigated the impact of VEGF gene (VEGFA) single nucleotide polymorphisms (SNPs) on treatment outcomes for AML. Four VEGFA SNPs were analysed for −2578C>A (rs699947), −460T>C (rs833061), +405G>C (rs2010963) and +936 C>T (rs3025039) loci in 138 AML patients. The +936 CC/CT genotype showed strong correlation with favourable leukaemia‐free survival (LFS) at 2u2003years (51·3%) versus with +936 CC genotype (33·6%, Pu2003=u20030·03). Strong linkage disequilibrium was noted among loci −2578, −460 and +405, but not with +936. Accordingly, four haplotypes were generated based on the genotypes of −2578, −460 and +405 as follows: CTC (40·2%), CTG (35·0%), ACG (22·0%) and ATC (1·2%). The LFS and event‐free survival (EFS) inversely correlated with CTG haplotype (Pu2003=u20030·03 for LFS; Pu2003=u20030·05 for EFS). We scored the VEGFA polymorphism marker based on +936 C>T genotype and CTG haplotype for −2578, −460 and +405, which demonstrated a good correlation with the treatment outcomes: LFS (Pu2003=u20030·01), EFS (Pu2003=u20030·03) and overall survival (Pu2003=u20030·01). The VEGFA +936 C>T genotype and CTG haplotype seemed to have an additive effect to predict the prognosis in AML patients.

Efficacy and Safety of Micafungin as an Empirical Antifungal Agent for Febrile Neutropenic Patients with Hematological Diseases

Background: This observational study was conducted to document the efficacy and safety of the use of micafungin (Mycamine) as an empirical antifungal agent in febrile neutropenic patients. Methods: Micafungin was administered for sustained fever (>38.4°C) on days 3–5 following the initiation of empirical antibiotic therapy. The overall success rate and side effects were evaluated. Results: A total of 47 patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome and lymphoma were enrolled in the study. The overall success rate of micafungin was 61.7% (29/47). A total of 3 patients (6.4%) experienced grade 3/4 elevations in their aspartate aminotransferase levels, and 10 patients (21%) experienced grade 3/4 hyperbilirubinemia, 9 of which resolved. Four patients died of septic shock. Younger patients (<50 years) and patients with acute lymphoblastic leukemia exhibited a better response to micafungin than other patients. Patients that were less profoundly neutropenic (≧0.05 × 109/l) also had a better response to micafungin, as did the patients who recovered from their fever or neutropenia. Conclusion: Micafungin has an excellent efficacy (61.7%) and safety profile when used as an empirical antifungal agent in febrile neutropenic patients with hematological disorders.

Allogeneic stem cell transplantation in patients with non-Hodgkin lymphoma who experienced relapse or progression after autologous stem cell transplantation

There are few treatment options for patients with non-Hodgkin lymphoma (NHL) who experienced progression after high-dose chemotherapy (HDC) with autologous stem cell transplantation (auto-SCT). The role of allogeneic stem cell transplantation (allo-SCT) in these patients has not been clarified yet. In this study, we report clinical outcomes of allo-SCT in patients with NHL who experienced progression after HDC with auto-SCT. Patients were enrolled from seven hospitals in Korea. A total of 38 patients were included: 18 patients (47.4%) underwent myeloablative conditioning and 20 patients (52.6%) reduced intensity conditioning. Overall response rate was 73.3%. Median event-free survival was 6.3xa0months. Median overall survival (OS) was 19.0xa0months. Estimated 5-year survival rate was 35.0%. Acute graft-versus-host disease developed in 13 patients (34.2%). Transplant-related mortality (TRM) was 21.1% (eight patients). Ann Arbor stage (pu2009=u20090.022), performance status (pu2009<u20090.001), and baseline serum albumin level (pu2009=u20090.010) were significant risk factors for OS. Performance status (pu2009=u20090.022) was a significant risk factor for TRM. Eight patients with persistent or progressive disease received donor lymphocyte infusion, and two of them achieved complete remission. In conclusion, despite high TRM, allo-SCT is a viable option for patients with NHL who underwent progression after HDC with auto-SCT.

A randomized trial of preemptive therapy for prevention of cytomegalovirus disease after allogeneic hematopoietic stem cell transplantation

We studied the efficacy of two different doses of ganciclovir to prevent cytomegalovirus (CMV) disease in allogeneic hematopoietic stem cell transplantation (HSCT) recipients. We randomly assigned allogeneic HSCT recipients who had CMV infection to receive preemptive ganciclovir therapy with or without induction phase (5xa0mg/kg twice daily for 1xa0week). Thirty-two and thirty-six patients were randomized to the standard and the low-dose therapy group, respectively. The median time to CMV antigenemia or viremia clearance was 7xa0days (3–25xa0days) in the standard therapy group versus 11xa0days (3–69xa0days) in the low-dose therapy group (Pxa0=xa00.540). The incidence of CMV disease was similar between the two groups (Pxa0=xa00.366). The Kaplan–Meier estimate of event-free survival by day 180 after HSCT was 76.2% in the standard therapy group versus 66.7% in the low-dose therapy group (Pxa0=xa00.590). Severe neutropenia (<0.5xa0×xa0109/L) was observed in four (12.5%) patients in the standard therapy group versus two (5.6%) patients in the low-dose therapy group (Pxa0=xa00.314). This study suggests that a low-dose ganciclovir preemptive therapy can be as effective as the standard-dose ganciclovir preemptive therapy for the prevention of CMV disease in allogeneic HSCT recipients.

Inclusion of hemoglobin level in prognostic score provides better prognostic stratification in patients with acute promyelocytic leukemia (APL)

The clinical outcomes of acute promyelocytic leukemia (APL) have improved greatly, but treatment failure still occurs. Identification of patients with poor prognosis is fundamental, and we propose a new clinical prognostic system (CBC-score) consisting of WBC, platelet count, and hemoglobin level. Between 1995 and 2009, 156 patients with APL from seven institutes in Korea were retrospectively reviewed. In the new CBC-score system, each of the following (WBC ≥10xa0×xa0109/L, platelet <40xa0×xa0109/L, hemoglobin <8.0xa0g/dL) was considered as a risk factor; the sum of each was designated as the CBC-score. With a median follow-up of 8.4xa0years, the complete remission (CR) rate was 81.4xa0% (127/156), while 24 (15.4xa0%) were considered as treatment failures due to early death (ED). The 5-year overall survival (OS), leukemia-free survival, and cumulative incidence of relapse were 73.8, 82.8, and 13.5xa0%, respectively. Compared to the individual CBC parameters, combined prognostic systems such as PETHEMA or CBC-score provided better prognostic stratification. Compared to PETHEMA stratification, the proposed prognostic CBC-score system showed better stratification of APL patients in terms of CR rates (pxa0=xa00.004), OS (pxa0=xa00.004), and ED (pxa0=xa00.008). This retrospective study suggests that the proposed CBC-score may provide better prognostic stratification of APL patients.

Early detection of marine invasive species, Bugula neritina (Bryozoa: Cheilostomatida), using species-specific primers and environmental DNA analysis in Korea

The bryozoan, Bugula neritina, is one of the most widespread sessile marine invasive species. Since its first discovery in Korea in 1978, the gradual increase in the distribution and abundance of this species resulted in a significant damage to growth of aquaculture. Environmental DNA (eDNA) is a potentially useful tool for species detection including rare, invasive and threatened native species. In this study, species-specific primers and probe were designed to amplify a 185-bp region based on mitochondrial COI of B. neritina for monitoring, and tested on environmental samples from 35 harbors of Korea in 2017. Among 35 sites monitored, B. neritina colonies were detected in 27 sites during field survey. However, B. neritina DNA was detected in all examined eDNA isolated from seawater. These results suggested that eDNA-based methods coupled with simple seawater sampling could be suitable for determining the distribution and abundance of B. neritina as complementary traditional monitoring.

A Newly Recorded Sea Star of the Genus Luidia (Asteroidea: Paxillosida: Luidiidae) from the Korea Strait, Korea

Asteroid specimens of the genus Luidia were collected at a depth of 95-100 m in the Korea Strait by bottom trawling in April 2016. The specimens were identified as Luidia avicularia Fisher, 1913 (Luidiidae: Paxillosida) based on morphological characteristics and molecular phylogenetic analyses, and the species is new to the Korean fauna. A 648xadbp partial nucleotide sequence of mitochondrial cytochrome c oxidase I (mtxadCOI) gene was obtained from Korea, and then was compared to sequences of related species stored in GenBank using molecular phylogenetic analyses. No sequence differences were detected between the L. avicularia mtxadCOI gene sequences from Korea and China, and the species described in this report was clearly distinct from L. maculata, which was previously reported in Korean fauna. Three Luidia species have been reported in Korea.