Treated chronic hepatitis B is a good prognostic factor of diffuse large B-cell lymphoma

Background/Aims@#Chronic hepatitis B (CHB) is a risk factor for non-Hodgkin lymphoma (NHL). Our recent study suggested that antiviral treatment may reduce the incidence of NHL in CHB patients. This study compared the prognoses of hepatitis B virus (HBV)-associated diffuse large B-cell lymphoma (DLBCL) patients receiving antiviral treatment and HBV-unassociated DLBCL patients. @*Methods@#This study comprised 928 DLBCL patients who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at two referral centers in Korea. All patients with CHB received antiviral treatment. Time-to-progression (TTP) and overall survival (OS) were the primary and secondary endpoints, respectively. @*Results@#Among the 928 patients in this study, 82 were hepatitis B surface antigen (HBsAg)-positive (the CHB group) and 846 were HBsAg-negative (the non-CHB group). The median follow-up time was 50.5 months (interquartile range [IQR]=25.6–69.7 months). Multivariable analyses showed longer TTP in the CHB group than the non-CHB group both before inverse probability of treatment weighting (IPTW; adjusted hazard ratio [aHR]=0.49, 95% confidence interval [CI]=0.29–0.82, p=0.007) and after IPTW (aHR=0.42, 95% CI=0.26–0.70, p<0.001). The CHB group also had a longer OS than the non-CHB group both before IPTW (HR=0.55, 95% CI=0.33–0.92, log-rank p=0.02) and after IPTW (HR=0.53, 95% CI=0.32–0.99, log-rank p=0.02). Although liver-related deaths did not occur in the non-CHB group, two deaths occurred in the CHB group due to hepatocellular carcinoma and acute liver failure, respectively. @*Conclusions@#Our findings indicate that HBV-associated DLBCL patients receiving antiviral treatment have significantly longer TTP and OS after R-CHOP treatment than HBV-unassociated DLBCL patients.

Clinicopathologic implication of PD-L1 gene alteration in primary adrenal diffuse large B cell lymphoma

Background@#Primary adrenal (PA) diffuse large B cell lymphoma (DLBCL) was previously reported as an aggressive subset of DLBCL, but its genetic features were not sufficiently characterized. From our previous study of DLBCL with programmed death-ligand 1 (PD-L1) gene alterations, we focused on PD-L1 gene alterations in PA-DLBCL with clinicopathologic implications. @*Methods@#We performed fluorescence in situ hybridization for PD-L1 gene translocation and amplification in PA-DLBCL (n = 18) and comparatively analyzed clinicopathologic characteristics with systemic non-adrenal (NA)-DLBCL (n = 90). @*Results@#PA-DLBCL harbored distinctive features (vs. NADLBCL), including high international prognostic index score (3–5) (72% [13/18] vs. 38% [34/90], p = .007), poor Eastern Cooperative Oncology Group performance score (≥ 2) (47% [7/15] vs. 11% [10/90], p = .003), elevated serum lactate dehydrogenase (LDH) (78% [14/18] vs. 51% [44/87], p = .035) and MUM1 expression (87% [13/15] vs. 60% [54/90], p = .047). Moreover, PA-DLBCL showed frequent PD-L1 gene alterations (vs. NA-DLBCL) (39% [7/18] vs. 6% [5/86], p = .001), including translocation (22% [4/18] vs. 3% [3/87], p = .016) and amplification (17% [3/18] vs. 2% [2/87], p = .034). Within the PA-DLBCL group, PD-L1 gene–altered cases (vs. non-altered cases) tended to have B symptoms (p = .145) and elevated LDH (p = .119) but less frequent bulky disease (≥ 10 cm) (p = .119). In the survival analysis, PA-DLBCL had a poor prognosis for overall survival (OS) and progression-free survival (PFS) (vs. NA-DLBCL; p = .014 and p = .004). Within the PA-DLBCL group, PD-L1 translocation was associated with shorter OS and PFS (p < .001 and p = .012). @*Conclusions@#PA-DLBCL is a clinically aggressive and distinct subset of DLBCL with frequent PD-L1 gene alterations. PD-L1 gene translocation was associated with poor prognosis in PA-DLBCL.

Multicenter retrospective analysis of patients with chronic lymphocytic leukemia in Korea

Background@#Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia in Western countries but is rare in the East Asian countries. Due to its rarity and the lack of feasible novel agents and laboratory prognostic tools, there are limited data on the clinical outcomes of this disease in Asia. To clarify the current treatment status, we performed a multicenter retrospective analysis of patients with CLL in Korea. @*Methods@#The medical records of 192 eligible patients between 2008 and 2019 were reviewed for clinical characteristics, treatment courses, and outcomes. The first-line treatment regimens of the patients included in this analysis were as follows: fludarabine/cyclophosphamide/rituximab (FCR) (N=117, 52.7%), obinutuzumab plus chlorambucil (GC) (N=30, 13.5%), and chlorambucil monotherapy (N=24, 10.8%). @*Results@#The median progression-free survival (PFS) was 55.6 months, and the average 2-year PFS rate was 80.3%. PFS was not significantly different between the patients receiving FCR and those receiving GC; however, chlorambucil treatment was associated with significantly inferior PFS (P ＜0.001). The median overall survival was 136.3 months, and the average 5- and 10-year OS rates were 82.0% and 57.4%, respectively. @*Conclusion@#This is one of the largest studies involving Korean patients with CLL. Although the patients had been treated with less favored treatment regimens, the outcomes were not different from those reported in Western studies.

R-MPV followed by high-dose chemotherapy with thiotepa-based and autologous stem cell transplantation for newly diagnosed primary central nervous system lymphoma: a single-center experience

Background@#High-dose chemotherapy followed by autologous stem cell transplantation (HDC-ASCT) as a consolidation treatment is a promising approach for eligible patients with newly diagnosed primary central nervous system lymphoma (PCNSL). @*Methods@#In this retrospective analysis, 22 patients with newly diagnosed PCNSL received chemotherapy with rituximab, methotrexate, procarbazine, and vincristine. Those who showed complete or partial response subsequently received consolidation HDC-ASCT with a thiotepa-based conditioning regimen but did not undergo radiotherapy. @*Results@#The PCNSL patients had a median age of 57 years (range, 49‒67 yr); of the total patients, 9.1% had a performance status of 2 or higher, and 72.1% had multiple lesions.Approximately 82% of patients received six cycles of induction chemotherapy, which was well tolerated with excellent disease control. The rate of confirmed or unconfirmed complete response increased from 45.5% at the period of interim analysis to 81.8% prior to the initiation of HDC-ASCT. With a median follow-up of 19.6 months (range, 7.5‒56.5 mo), the 2-year progression-free survival and overall survival estimates were 84% and 88%, respectively. No treatment-related deaths occurred. Grade 3 toxicity was recorded in 90.9% of the patients after undergoing the HDC-ASCT, and the most common grade 3 adverse event was febrile neutropenia without sepsis. @*Conclusion@#The discussed treatment approach is feasible in patients with newly diagnosed PCNSL, yielding encouraging results.

Prominent seasonal variation in pulmonary embolism than deep vein thrombosis incidence: a Korean venous thrombosis epidemiology study

Background/Aims@#Seasonal variation is an environmental factor proposed to affect the incidence of venous thromboembolism (VTE). However, VTE seasonal variation is not well studied in Asian populations, which have different genetic determinants of VTE compared to Westerners. The present study aimed at investigating seasonal variation of VTE occurrence and the effect of various demographic factors (i.e., age, sex, and co-morbidities) on variation. @*Methods@#VTE seasonal variation was evaluated in 59,626 index cases (from January 2009 to December 2013) in the Korean Health Insurance Review and Assessment Service database. We quantified and compared VTE occurrence across four seasons, and additionally assessed monthly through a chronobiological analysis. @*Results@#VTE incidence varied both seasonally and monthly, with new cases peaking in the winter (January and February) and the lowest incidence in the summer (August and September). After adjusting for sex, age, type of VTE, and combined cancer diagnosis, winter remained a significant independent factor driving VTE incidence. Additionally, seasonal variation was prominent in patients aged 60 years or older and in patients with pulmonary embolism, but not so prominent in patients of aged less than 60 years and patients with deep vein thrombosis. @*Conclusions@#Seasonal variation was a weak but independent contributor to VTE incidence in a Korean population diagnosed from 2009 to 2013, especially in those individuals with old age or suffering from a pulmonary embolism.

Similar transplant outcomes between haploidentical and unrelated donors after reduced-intensity conditioning with busulfan, fludarabine, and anti-thymocyte globulin in patients with acute leukemia or myelodysplastic syndrome

BACKGROUND: Although T-cell-replete hematopoietic cell transplantation (HCT) from haploidentical donors (HIDs) using anti-thymocyte globulin (ATG) has shown promising outcomes, previous studies often adopted heterogenous graft sources and conditioning.METHODS: We retrospectively compared HCT outcomes from 62 HIDs, 36 partially-matched unrelated donors (PUDs), and 55 matched unrelated donors (MUDs) in patients with acute leukemia or myelodysplastic syndrome using the same graft source of peripheral blood and a reduced intensity conditioning of busulfan, fludarabine, and ATG.RESULTS: The estimates of 3-yr disease-free survival (DFS) and overall survival (OS) rates were not significantly different among the MUD, HID, and PUD groups, at 46%, “41%, and 36%” for the DFS rate (P=0.844), and 55%, 45%, and 45% for the OS rate (P=0.802), respectively. Cumulative incidence of relapse and non-relapse mortality at 3 yr was similar among different donor types. Subsequent multivariable analyses showed that the sex of the patient (male) and a high/very high disease risk index were independently associated with poorer DFS and OS, while the donor type was not.CONCLUSION: T-cell replete HCT from HIDs using an ATG-containing reduced intensity conditioning regimen may be a reasonable option in the absence of matched related donors in patients with acute leukemia or myelodysplastic syndrome.

Body Cavity–Based Lymphoma in a Country with Low Human Immunodeficiency Virus Prevalence: A Series of 17 Cases from the Consortium for Improving Survival of Lymphoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Primary effusion lymphoma (PEL) is a type of body cavity–based lymphoma (BCBL). Most patients with PEL are severely immunocompromised and seropositive for human immunodeficiency virus (HIV). We investigated the distinctive clinicopathologic characteristics of BCBL in a country with low HIV burden. MATERIALS AND METHODS: We retrospectively collected data on the clinicopathologic characteristics, treatments, and outcomes of 17 consecutive patients with BCBL at nine institutions in Korea. RESULTS: Latency-associated nuclear antigen 1 (LANA1) immunostaining indicated that six patients had PEL, six patients had human herpesvirus 8 (HHV8)-unrelated BCBL, and five patients had HHV8-unknown BCBL. The patients with PEL exhibited no evidence of immunodeficiency except for one who was HIV positive. One (20%) and four (80%) patients with PEL and six (100%) and zero (0%) patients with HHV8-unrelated BCBL were positive for CD20 and CD30 expression, respectively. The two patients with PEL (one HIV-positive and one HIV-negative patient) with the lowest proliferation activity as assessed by the Ki-67 labeling index survived for > 1 and > 4 years without chemotherapy, respectively, in contrast to the PEL cases in the literature, which mostly showed a high proliferation index and poor survival. CONCLUSION: PEL mostly occurred in ostensibly immunocompetent individuals and had a favorable outcome in Korea. A watchful waiting approach may be applicable for managing HIV-seronegative patients with PEL with a low Ki-67 labeling index. A possible trend was detected among LANA1, CD20, and CD30 expression in BCBL.

Effect of Platinum-Based Chemotherapy on PD-L1 Expression on Tumor Cells in Non-small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Programmed death-1 (PD-1)/PD-1 ligand (PD-L1) axis blockades have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). We assessed the effect of platinum-based chemotherapy on tumor PD-L1 expression and its clinical implications. MATERIALS AND METHODS: We used immunohistochemistry to retrospectively evaluate the percentage of tumor cells with membranous PD-L1 staining (tumor proportion score) in paired tumor specimens obtained before and after platinum-based neoadjuvant chemotherapy (NACT) in 86 patients with NSCLC. We analyzed the correlation between the change in PD-L1 tumor proportion score and clinicopathologic characteristics, response to NACT, and survival. RESULTS: The PD-L1 tumor proportion score increased in a significant proportion of patients with NSCLC after platinum-based NACT (Wilcoxon signed-rank test, p=0.002). That pattern was consistent across clinically defined subgroups except for patients with partial response to NACT. Tumors from 26 patients (30.2%) were PD-L1‒negative before NACT but PD-L1-positive after NACT, whereas the reverse pattern occurred in six patients (7%) (McNemar’s test, p < 0.001). Increase in PD-L1 tumor proportion score was significantly associated with lack of response to NACT (Fisher exact test, p=0.015). There was a tendency, albeit not statistically significant, for patients with an increase in PD-L1 tumor proportion score to have shorter survival. CONCLUSION: Tumor PD-L1 expression increased after platinum-based NACT in a significant proportion of patients with NSCLC. Increase in tumor PD-L1 expression may predict poor clinical outcome.

Predictors of Cognitive Improvement during 12 Weeks of Antidepressant Treatment in Patients with Major Depressive Disorder

OBJECTIVE: Cognitive disturbance is one of the major symptoms of depression and may be improved by treatment with antidepressants. This study aimed to investigate the predictors of cognitive improvement in patients with major depressive disorder (MDD) who were taking antidepressants. METHODS: This study included 86 patients with MDD who completed 12 weeks of antidepressant monotherapy. Cognitive symptoms were assessed using the Perceived Deficits Questionnaire-Korean version (PDQ-K), which addresses four domains of cognitive functioning (attention/concentration, retrospective memory, prospective memory, and organization/planning) and was administered at study entry and at the 12-week end point. A variety of demographic, clinical, and treatment-related variables were evaluated as predictors of changes in total and domain scores. RESULTS: All PDQ-K domains showed significant improvement after 12 weeks of antidepressant treatment. More severe initial depressive symptoms, fewer sick-leave days at study entry, and reduced use of concomitant anxiolytics/hypnotics during treatment were significantly associated with greater cognitive improvement. CONCLUSION: Cognitive symptoms are more responsive to antidepressant treatment in patients with severe MDD. Reduced use of anxiolytics and hypnotics could improve the cognitive functioning of patients with MDD taking antidepressants.

Comparison of Plasma Concentrations of Posaconazole with the Oral Suspension and Tablet in Korean Patients with Hematologic Malignancies

The posaconazole tablet formulation was developed to have improved bioavailability compared to the oral suspension. Here, we compared posaconazole plasma concentration (PPC) with the posaconazole oral suspension versus the tablet in Korean patients undergoing remission induction chemotherapy for hematologic malignancies. PPC was measured at 3, 8, and 15 days of treatment with the oral suspension (174 patients) or the tablet (40 patients). At all time-points, mean PPC was significantly higher with the tablet compared to the oral suspension. Our findings suggest that posaconazole tablets generate an optimal PPC earlier and in more patients than the oral suspension among Korean patients.

Dapsone therapy for refractory immune thrombocytopenia patients: a case series

BACKGROUND: Dapsone has been recommended as a second-line immunosuppressive agent for patients with immune thrombocytopenia (ITP). METHODS: We retrospectively analyzed the efficacy and safety of dapsone therapy in patients with ITP. RESULTS: Nine ITP patients were treated with dapsone at a dose of 50–100 mg/day between May 2013 and March 2016. All patients were refractory to multiple previous treatments, with a median of 7 agents (range, 4–8), and 3 patients had undergone a previous splenectomy. The median pre-treatment platelet count was 4×10⁹/L (range, 3–27×10⁹/L). Only 1 patient (11.1%) responded to dapsone therapy. No severe adverse events were observed, except for 1 case of dapsone hypersensitivity syndrome. CONCLUSION: Although dapsone is still useful for some patients, it may be ineffective in heavily pretreated patients with profound thrombocytopenia.

Human Herpesvirus 8–Unrelated Primary Effusion Lymphoma–Like Lymphoma in an Elderly Korean Patient with a Good Response to Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone / Journal of the Korean Cancer Association, 대한암학회지

Primary effusion lymphoma (PEL) is a rare type of non-Hodgkin’s lymphoma arising from a B-cell lineage characterized by the formation of malignant effusion in body cavities without evidence of a detectable tumor. The effusion contains tumor cells universally infected with human herpesvirus 8 (HHV8), which is the critical factor differentiating PEL from HHV8-unrelated PEL-like lymphoma (PEL-LL). This report describes a 77-year-old male patient with pleural effusion and ascites, containing lymphoma cells expressing a B-cell phenotype, but without markers of HHV8 in immunocytochemical analysis. The patient was diagnosed with PEL-LL and treated with six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP), which resulted in a complete remission. The patient is currently disease-free 15 months post-treatment. To the best of our knowledge, this is the first report on administration of R-CHOP in a PEL-LL patient in South Korea.

Incidence, Survival and Prevalence Statistics of Classical Myeloproliferative Neoplasm in Korea

The nationwide statistical analysis of each disease of classical myeloproliferative neoplasm (MPN) in Korea has not been reported yet. To this end, we have analyzed incidence rates, survival rates and treatment pattern of polycythemia vera (PV), primary myelofibrosis (MF) and essential thrombocythemia (ET) using Korea National Cancer Incidence Database (KNCIDB) and Health Insurance Review and Assessment Service (HIRA) database. Between 2003 and 2011, a total of 4,342 new cases of MPN were reported to the KNCIDB. ET was the most common, followed by MF and PV. The crude incidence rates for PV, MF, and ET have increased during the period, reaching 0.40, 0.15, and 0.84 per 100,000, respectively. Five-year relative survival rate of all MPN patients was 89.3%, with lowest relative survival rate with MF (53.1%). The prevalence of each disease estimated from HIRA data also increased during the study period. Notably, ET was found to be most prevalent. The prescription rate of hydroxyurea and phlebotomy to PV, MF and ET patients remained constant over the period, and the prescription rate of hydroxyurea was higher in patients with age over 60 years. This is the first Korean nationwide statistics of MPN, using central registry data. This set of data can be utilized to compare the Korean MPN status to international data and guidelines.

Gefitinib-Induced Interstitial Lung Disease in Korean Lung Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Interstitial lung disease (ILD) is a serious adverse effect of gefitinib. We examined the incidence and clinical characteristics of drug-induced ILD in Korean non-small cell lung carcinoma patients treated with gefitinib. MATERIALS AND METHODS: A retrospective cohort study was performed in non-small cell lung cancer (NSCLC) patients who started gefitinib treatment at Seoul National University Hospital from January 2002 through December 2011. Patients who developed new abnormal radiologic findings with respiratory symptoms after gefitinib treatment were defined as having possible adverse pulmonary reactions. The patients' medical records were reviewed independently by investigators to identify the causes of pulmonary toxicities. RESULTS: Among the 1,114 patients evaluated, 128 patients (11.5%) developed pulmonary adverse reactions after taking gefitinib. An infectious complication occurred in 98 patients (8.8%) and 15 patients (1.3%) developed ILD. Nine of the 15 patients (60.0%) with gefitinib-induced ILD experienced a fatal clinical course that met either the Common Terminology Criteria for Adverse Events grade 4 (n=3) or grade 5 (n=6). In the multivariate analysis, a lower serum albumin level (< or = 3.0 g/dL) at baseline was significantly associated with the development of gefitinib-induced ILD (odds ratio, 3.91; 95% confidence interval, 1.20 to 12.71). CONCLUSION: The incidence of gefitinib-induced ILD in Korean NSCLC patients was similar to that reported worldwide, but lower than values reported for Japanese population. ILD was usually a life-threatening adverse effect of gefitinib, and the development of ILD was significantly associated with a lower baseline serum albumin level.

Prospective Study on the Incidence of Postoperative Venous Thromboembolism in Korean Patients with Colorectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Pharmacologic thromboprophylaxis is routinely recommended for Western cancer patients undergoing major surgery for prevention of venous thromboembolism (VTE). However, it is uncertainwhetherroutine administration of pharmacologic thromboprophylaxis is necessary in all Asian surgical cancer patients. This prospective study was conducted to examine the incidence of and risk factors for postoperative VTE in Korean colorectal cancer (CRC) patients undergoing major abdominal surgery. MATERIALS AND METHODS: This study comprised two cohorts, and none of patients received perioperative pharmacologic thromboprophylaxis. In cohort A (n=400), patients were routinely screened for VTE using lower-extremity Doppler ultrasonography (DUS) on postoperative days 5-14. In cohort B (n=148), routine DUS was not performed, and imaging was only performed when there were symptoms or signs that were suspicious for VTE. The primary endpoint was the VTE incidence at 4 weeks postoperatively in cohort A. RESULTS: The postoperative incidence of VTE was 3.0% (n=12) in cohort A. Among the 12 patients, eight had distal calf vein thromboses and one had symptomatic thrombosis. Age ≥ 70 years (odds ratio [OR], 5.61), ≥ 2 comorbidities (OR, 13.42), and white blood cell counts of > 10,000/μL (OR, 17.43) were independent risk factors for postoperative VTE (p < 0.05). In cohort B, there was one case of VTE (0.7%). CONCLUSION: The postoperative incidence of VTE, which included asymptomatic cases, was 3.0% in Korean CRC patients who did not receive pharmacologic thromboprophylaxis. Perioperative pharmacologic thromboprophylaxis should be administered to Asian CRC patients on a risk-stratified basis.

Intravenous tacrolimus and cyclosporine induced anaphylaxis: what is next?

Tacrolimus and cyclosporine have been used in various formulations, but their hypersensitivity reactions are rare in practice. Castor oil derivatives are nonionic surfactants used in aqueous preparations of hydrophobic active pharmaceutical ingredients. Castor oil derivatives that can be used as additives to tacrolimus and cyclosporine may play a role in the development of hypersensitivity reactions, especially anaphylaxis. Various immunologic and nonimmunologic mechanisms have been implicated in hypersensitivity reactions induced by castor oil derivatives. Physicians should be aware that not only the drug itself, but also its additives or metabolites could induce hypersensitivity reactions. We report a case of anaphylaxis caused by vitamin K (phytonadine), serotonin antagonist (granisetron), intravenous tacrolimus, and cyclosporine. Interestingly, the patient tolerated oral cyclosporine, which did not contain Cremophor EL or polysorbate 80.

Korean Guidelines for Treating Chronic Myelogenous Leukemia - The Korean Society of Hematology Chronic Myelogenous Leukemia Working Party / 대한내과학회지

BACKGROUND/AIMS: The first edition of the Korean treatment guidelines for chronic myelogenous leukemia (CML) was published in 2006. We intend to update those guidelines to include the use of next-generation tyrosine kinase inhibitors (TKIs). METHODS: New guidelines were developed in 2012 based on the results of a survey and a consensus meeting of various Korean experts, the reports of recent clinical studies, and updated guidelines from external study groups. RESULTS: An assessment of risk factors is strongly recommended before treating newly diagnosed chronic phase CML. Imatinib, dasatinib, and nilotinib are reimbursable in Korea as first-line treatments, and the patient's age, comorbidities, and possible adverse events should be considered in the choice of treatment. Molecular studies are recommended for assessing treatment efficacy instead of invasive cytogenetic response evaluations, and an early response is believed to correlate with a good prognosis. Second-line TKIs can be considered for patients who fail or are intolerant of first-line therapy, pending analysis of ABL tyrosine kinase mutation status. For treating advanced stages, a combination of TKIs with cytotoxic agents and hematopoietic cell transplantation is recommended. The adverse effects of TKI therapy can be managed via dose reduction and supportive care, or switching to an alternate TKI. CONCLUSIONS: The use of TKIs has improved the outcome of CML treatment. Treatment-free remission after discontinuing TKIs might be possible in select patients who achieve sufficient response, indicating that curative treatment for CML can be expected in the future.

Maximum standardized uptake value on positron emission tomography/computed tomography predicts clinical outcome in patients with relapsed or refractory diffuse large B-cell lymphoma

BACKGROUND: Few clinical studies have clarified the prognostic factors that affect clinical outcomes for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after immunochemotherapy. METHODS: A total of 158 patients with relapsed or refractory DLBCL were enrolled. All patients underwent positron emission tomography/computed tomography (PET/CT) before and after salvage therapy. All enrolled patients previously received the ifosfamide, carboplatin, and etoposide regimen. Clinical outcomes were compared according to several factors (age > or = 65 years, low age-adjusted International Prognostic Index [aa-IPI], maximum standardized uptake value [SUVmax] or =12 months, complete response after salvage therapy). A low aa-IPI, SUVmax or = 12 months were independent prognostic factors for survival. RESULTS: In univariate analysis and multivariate analysis, SUVmax below 6.0 (P<0.001 for progression-free survival (PFS), P<0.001 for overall survival (OS)) and low aa-IPI (P<0.001 for PFS, P<0.001 for OS) were independent prognostic factors associated with favorable outcome. CONCLUSION: The aa-IPI and initial SUVmax were powerful prognostic factors in patients with relapsed or refractory DLBCL.

p21-Activated Kinase 4 (PAK4) as a Predictive Marker of Gemcitabine Sensitivity in Pancreatic Cancer Cell Lines / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: p21-activated kinases (PAKs) are involved in cytoskeletal reorganization, gene transcription, cell proliferation and survival, and oncogenic transformation. Therefore, we hypothesized that PAK expression levels could predict the sensitivity of pancreatic cancer cells to gemcitabine treatment, and PAKs could be therapeutic targets. MATERIALS AND METHODS: Cell viability inhibition by gemcitabine was evaluated in human pancreatic cancer cell lines (Capan-1, Capan-2, MIA PaCa-2, PANC-1, Aspc-1, SNU-213, and SNU-410). Protein expression and mRNA of molecules was detected by immunoblot analysis and reverse transcription polymerase chain reaction. To define the function of PAK4, PAK4 was controlled using PAK4 siRNA. RESULTS: Capan-2, PANC-1, and SNU-410 cells were resistant to gemcitabine treatment. Immunoblot analysis of signaling molecules reported to indicate gemcitabine sensitivity showed higher expression of PAK4 and lower expression of human equilibrative nucleoside transporter 1 (hENT1), a well-known predictive marker for gemcitabine activity, in the resistant cell lines. Knockdown of PAK4 using siRNA induced the upregulation of hENT1. In resistant cell lines (Capan-2, PANC-1, and SNU-410), knockdown of PAK4 by siRNA resulted in restoration of sensitivity to gemcitabine. CONCLUSION: PAK4 could be a predictive marker of gemcitabine sensitivity and a potential therapeutic target to increase gemcitabine sensitivity in pancreatic cancer.

Five-Year Follow-up Study of Monoclonal Gammopathy of Undetermined Significance in a Korean Elderly Urban Cohort / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We previously reported the prevalence of monoclonal gammopathy of undetermined significance (MGUS) to be 3.3% among an elderly Korean urban cohort recruited during 2005-2006. Here, we report a 5-year follow-up study of the previously identified MGUS cohort. MATERIALS AND METHODS: The 680 participants from the initial cohort were followed-up for a median of 5 years. Sera were collected between 2010 and 2011. Two-step screening was performed with standard serum electrophoresis followed by immunofixation and determination of the serum concentration of monoclonal-protein (M-protein). RESULTS: Of the 680 participants (21 with MGUS), 348 (51%) agreed to participate in the follow-up study and 10 were found to have MGUS. Among the 21 MGUS patients initially identified, nine were followed-up, six had persistent M-protein, and one patient had progressed to multiple myeloma (progression rate, 1.0%/yr). The M-protein disappeared in the remaining two individuals. Among the 339 participants without MGUS who were followed-up, four developed an M-protein. There was no significant difference in survival with respect to the presence of MGUS (p=0.66). CONCLUSION: The 5-year follow-up data show that the natural clinical course of MGUS in Korea is similar to that in Western countries. MGUS was not associated with an increased risk of death over the 5-year study period.