Jung Yong Hong

EBV-positive diffuse large B-cell lymphoma in young adults: is this a distinct disease entity?

BACKGROUNDnEpstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) of the elderly is defined only in adults older than 50 years. However, EBV-positive DLBCL can affect younger patients. We investigated the prevalence, clinical characteristics and survival outcomes of EBV-positive DLBCL in young adults.nnnPATIENTS AND METHODSnWe analyzed patients with de novo DLBCL who were registered in the Samsung Medical Center (SMC) retrospective lymphoma cohort and prospective SMC Lymphoma Cohort Study I (ClinicalTrials.gov: NCT00822731).nnnRESULTSnA total of 571 cases were included in the analysis. The prevalence of EBV positivity was 6.7% (13/195) and 9.3% (35/376) in the young group (≤50 years) and in the elderly group (>50 years), respectively. EBV status was closely associated with unique unfavorable clinical characteristics [older age, more advanced stage, two or more sites of extranodal involvement, higher International Prognostic Index (IPI), and age-adjusted IPI risk] only in the elderly group. Poor prognostic impact of EBV positivity on overall survival was observed only in the elderly group [hazard ratio (HR) 2.86; 95% confidence interval (CI) 1.83-4.47; P < 0.001], but not in the young group (HR 1.17; 95% CI 0.35-3.89; P = 0.801).nnnCONCLUSIONnA substantial proportion of EBV-positive DLBCL of the elderly can occur in young adults. EBV positivity of DLBCL in young adults was not associated with unfavorable clinical characteristics or worse outcomes. We suggest that EBV-positive DLBCL should not be confined only in the elderly and EBV-positive DLBCL in young adults needs to be considered as a clinically distinct disease entity. ClinicalTrials.gov: NCT02060435.

TTP-HUS associated with sunitinib.

Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is a rare condition that is severe and may be fatal. Adverse reactions to drugs increasingly are reported as probable causes of TTP-HUS. Many chemotherapeutic agents have also been implicated in causing TTP-HUS. We reported a woman with metastatic renal cell carcinoma who presented with TTP-HUS associated with sunitinib. She had gross hematuria and generalized edema. The hemoglobin concentration was 8.9 g/dl and the platelet count was 46,000/mm(3). Her reticulocyte count was increased to 4.1% and the peripheral blood smear revealed red blood cell fragmentation and spherocytes. The patient completely recovered after discontinuing the use of sunitinib and undergoing plasmapheresis. Because of the increasing use of sunitinib in the treatment of cancer patients, oncologists should be aware of the possibility of TTP-HUS related to sunitinib, as early recognition and prompt therapeutic intervention can be beneficial.

Effect of paclitaxel/carboplatin salvage chemotherapy in noncutaneous versus cutaneous metastatic melanoma.

Little is known about the efficacy of salvage chemotherapy for patients with metastatic, noncutaneous melanoma after the failure of dacarbazine-based chemotherapy. Because of the high incidence of noncutaneous melanoma in Korea, we assessed the outcomes of paclitaxel/carboplatin (PC) salvage chemotherapy in patients with noncutaneous metastatic melanoma. We retrospectively analyzed patients with metastatic melanoma who received intravenous paclitaxel (175 mg/m2) plus intravenous carboplatin (area under the curve 5) on day 1 of a 21-day cycle as salvage chemotherapy at Samsung Medical Center (SMC) between February 2009 and February 2012. The overall response rate, overall survival, and progression-free survival were evaluated. Thirty-two patients with a median age of 54 years (range 24–72 years) received PC as salvage chemotherapy. All patients had been pretreated with a median of three systemic chemotherapies. Of the 32 patients, 10 (31.3%) had cutaneous melanoma, eight (25%) had acral melanoma, 10 (31.3%) had mucosal melanoma, and two (6.3%) had ocular melanoma. In response to treatment, seven of the 32 patients (21.9%) achieved partial response and 11 (34.4%) had stable disease. The median progression-free survival was 2.53 months for all patients, 4.3 months for patients with controlled disease (partial response and stable disease), and 1.37 months for patients with progressive disease (P=0.0001). The median overall survival was 5.2 months. No significant difference was noted between patients with noncutaneous and cutaneous metastatic melanoma (P=0.75). PC salvage chemotherapy may be a reasonable therapeutic option for heavily pretreated metastatic melanoma patients. Salvage therapy with this combination had definite clinically meaningful benefits in patients with metastatic melanoma, including those with noncutaneous melanoma.

Positive Correlation between Baseline PET or PET/CT Findings and Clinical Parameters in Multiple Myeloma Patients

Recently, positron emission tomography (PET) has been incorporated into a series of prospective studies as a predictor of outcomes in multiple myeloma (MM), and the number of 18F-fluorodeoxuglucose (FDG)-avid focal lesions (FLs) and the intensity of tumor metabolism have been designated as important surrogate markers for predicting prognosis. Here, we compared initial clinical characteristics of MM patients with baseline PET parameters: the number of FLs and the maximum standardized uptake value (SUVmax). A total of 59 patients diagnosed with MM between August 2004 and February 2012 were reviewed. At diagnosis, 23 patients (40.0%) had ≤3 FLs, 11 patients (18.6%) 4-9 FLs, and 25 patients (42.4%) ≥10 FLs. The median SUVmax was 5.3 (range 0-24.3), and 40 patients (67.8%) showed a SUVmax >4. No clinical characteristics were significantly different between groups with a SUVmax ≤4 and a SUVmax >4. However, there were significant differences in several clinical indices between the FLs ≤3 and FLs >3 groups; elevated β2-microglobulin, elevated lactate dehydrogenase, anemia and more advanced disease by the Durie-Salmon stage corresponded to FLs >3 at baseline PET. Adverse baseline PET findings are positively correlated with prognostically relevant clinical parameters. Regarding PET parameters, FLs are more likely to be well correlated with disease aggressiveness and pathophysiology compared to SUVmax.

Clinical Features and Treatment Outcomes of Intravascular Large B-Cell Lymphoma: A Single-Center Experience in Korea

Background: Clinical features and treatment outcomes of intravascular large B-cell lymphoma (IVLBCL) have rarely been reviewed due to its rarity and pathologic obscurity. Methods: We analyzed 20 patients who were pathologically diagnosed with IVLBCL at the Samsung Medical Center. Results: Initial manifestations were nonspecific, such as fever with cytopenia, elevated serum lactate dehydrogenase and hypoalbuminemia. Hemophagocytosis was frequent and bone marrow was the most common site of pathologic diagnosis in our series. Hepatosplenomegaly, pleural effusion and ground-glass opacity in the lungs were also commonly found, and positron emission tomography imaging showed increased 18F-fluorodeoxyglucose uptake in the involved organs. All patients received CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or rituximab-CHOP. The median overall survival (OS) was 38.9 months (95% confidence interval 6.7-71.1). Rituximab-containing chemotherapy compared to chemotherapy alone resulted in higher 3-year OS (71.4 and 25.0%; p = 0.027). Patients with hemophagocytosis had a poorer 3-year OS compared to patients without hemophagocytosis (29.6 and 75%; p = 0.046). Prognostic factor analysis showed the association of pleural effusion with worse OS (p = 0.002). Conclusions: Treatment with rituximab-containing chemotherapy can improve the treatment outcome of IVLBCL. Pleural effusion may be a poor prognostic factor in patients with IVLBCL.

Serum survivin and vascular endothelial growth factor in extranodal NK/T-cell lymphoma, nasal type: implications for a potential new prognostic indicator

Extranodal natural killer/T-cell lymphoma (ENKTL) is an aggressive subtype of non-Hodgkin lymphoma showing frequent resistance to anthracyclines.[1][1] Although intensified, non-anthracycline-based chemotherapy regimens have improved clinical outcomes, the prognosis of ENKTL, especially advanced

Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly: a concise review and update.

Purpose of review Epstein–Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) of the elderly is an EBV-positive monoclonal large B-cell proliferative disease that arises in elderly patients older than 50 years. Updated knowledge on geographical/ethnical variations in the prevalence and prognostic impact of EBV positivity, the genetic mechanisms of lymphomagenesis, and the validity of the disease is available. Recent findings The poor prognostic impact of EBV positivity is consistent among Asian populations, but not in Western populations. CD30 may be associated with this geographical/ethnical variation. Gene expression analyses have confirmed the enhanced activity of the NF-&kgr;B and JAK/STAT pathways and more frequent expression of CD30 in EBV-positive DLBCL of the elderly. A substantial proportion of cases of EBV-positive DLBCL of the elderly occur in young immunocompetent adults; moreover, EBV-positive DLBCL in young adults has a distinct clinical course compared with EBV-positive DLBCL of the elderly. Summary Further research is anticipated, as follows: first, identifying geographical/ethnical differences in gene expression profiles and CD30 coexpression in EBV-positive DLBCL of the elderly; second, feasibility of the revision of the current disease entity confined to elderly patients; and third, novel therapeutic approaches targeting CD30 and the NF-&kgr;B and JAK/STAT pathways in EBV-positive DLBCL of the elderly.

Brentuximab vedotin for relapsed or refractory CD30+ Hodgkin lymphoma: a multicenter analysis from Asia

Introduction Brentuximab vedotin (SGN-35), an anti-cluster of differentiation (CD)-30 antibody conjugated to the anti-tubulin agent monomethyl auristatin E, has demonstrated promising efficacy and tolerability in relapsed and heavily treated Hodgkin lymphoma (HL). In this study, we report the Asian experience with brentuximab vedotin in patients with relapsed or refractory CD30-positive (CD30+) HL. Methods This is an observational, multicenter, retrospective study. Between October 2011 and June 2013, a total of 22 patients were treated with brentuximab vedotin under a named patient program in Asia. Patients received a 30 min infusion of brentuximab vedotin at a dose of 1.8 mg/kg of body weight every 3 weeks. Results Four patients (18.2%) showed a complete response, and the overall response rate was 72.7%. The median duration of response was 4.4 months (range 1.0–17.4). The median progression-free survival was 5.7 months, and the median overall survival has not yet been reached. The 1-year expected survival rate was 67.2%. The most common grade 3/4 adverse events were neutropenia (n=7; 31.8%). No patients experienced grade 3/4 sensory neuropathy. Conclusions These results confirm that brentuximab vedotin as a single agent is also effective and well tolerated when used in Asian patients with relapsed and refractory CD30+ HL.

Clinical impact of serum survivin positivity and tissue expression of EBV-encoded RNA in diffuse large B-cell lymphoma patients treated with rituximab–CHOP

Survivin is an inhibitor of apoptosis and is upregulated by Epstein–Barr virus (EBV) latent genes. Given the frequent association of EBV with lymphoid malignancies, survivin is expected to have prognostic value in diffuse large B-cell lymphoma (DLBCL). Thus, we measured the pretreatment serum level of survivin in DLBCL patients and analyzed its association with survival outcome and EBV status, as represented by EBV-encoded RNA (EBER) in DLBCL. Pretreatment serum survivin level was measured in patients registered in a prospective cohort study (n = 210), and serum survivin-positivity was defined as any detectable level of survivin. EBV status was determined using EBER in situ hybridization, and EBER-positivity was defined as 20% of examined cells showing nuclear positivity. Mean serum survivin level was higher in patients with relapsed or refractory disease than with responsive disease (59.89 pg/mL versus 17.34 pg/mL, P = 0.041). Serum survivin-positive patients had worse overall and progression-free survival (P = 0.023 and 0.022, respectively). Serum survivin positivity was associated with unfavorable characteristics including stage. In patients with non-germinal center B-cell type DLBCL, serum survivin-positive patients also had significantly worse survival than serum survivin-negative patients (P < 0.001). EBER-positivity was found in 6.7% (14/210) of patients, and EBER-positive patients had worse survival (P < 0.05). Patients having concomitant positivity for serum survivin and EBER expression (2.8%, 6/210) showed extremely poor prognosis. In the present era of rituximab in DLBCL, DLBCL with serum survivin positivity showed adverse clinical features and followed worse clinical course, especially in non-GCB subtype DLBCL. EBER-positivity was still associated with worse outcomes in DLBCL.

The NEEDLELESS MICROJET: a novel device for hypertrophic scar remodelling on the forehead

skin barrier, leading to ichthyosis with variable phenotypic severity. Functional studies conducted on mutations in ALOX12B and ALOXE3 in patients with ARCI demonstrated that the disruption of the c-terminal catalytic lipoxygenase domain results in a non-functional peptide with mostly mild to moderate ARCI phenotypes similar to the ones observed in our patient. It is therefore very likely that the mutation p.Asn582Argfs*24, which affects the catalytic helix 25 domain of the c-terminal is a loss-of-function mutation which either reduces enzyme activity or ablates protein synthesis. However, the restoration of the epidermal confiscation after birth suggests that the mutation could result in a protein misfolding that affects the enzyme activity primarily under in utero conditions due to the high hydrostatic water pressure as shown previously with TGM1 mutations. In summary, we find it convincing that the novel deletion mutation c.1745_1749del p.Asn582Argfs*24 in the ALOX12B gene is the cause of the clinical features of ichthyosis in the affected children. However, functional studies could be done to confirm the pathogenicity of this mutation. This report also adds information on the clinical picture of ARCI caused by ALOX12B mutations.