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Pembrolizumab (anti-programmed cell death-ligand 1 inhibitor) is a promising salvage therapeutic option for relapsed/refractory extranodal NK/T-cell lymphoma (R/R ENKTL). However, the appropriate duration of pembrolizumab use in R/R ENKTL patients and the optimal timing for administering pembrolizumab remain undetermined. We collected and analyzed clinical information on R/R ENKTL 58 patients who received pembrolizumab to evaluate the optimal treatment durations and clinical information for considering treatment interruption. Treatment outcomes were assessed by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) and Epstein Barr virus DNA (EBV DNA) every 3 months. Nineteen (32.8%) patients had been treated with more than three chemotherapies before pembrolizumab administration. The best response rate towards the first try of pembrolizumab was 38.9% (31.5% complete response rate (CR), 7.4% partial response (PR)). During the 41.8-month median follow-up duration, the median progression-free survival (PFS) was 3.1 months, and the median overall survival (OS) was 7.1 months. The failure group, which was characterized by Deaville score (DS) 3-4 and circulating EBV detection, or DS 5 with/without EBV detection, had the worst PFS (p < 0.001) and OS (p < 0.001), followed by the high (DS 1-2 and EBV detection, or DS 3-4 and EBV not detected) and low-risk groups (DS 1-2 and EBV not detected). Among the 21 patients who achieved the best response at the first pembolizumab try, the patients who received planned 24 cycles presented better PFS than those who received incomplete cycles (57.6 months vs 20.9 months, P-value = 0.012). Among 13 patients who received avelumab or pembrolizumab in advance, a few who responded to the second trial of pembrolizumab administration had over one year of chemotherapy vacation. Determining the discontinuation or continuation of pembrolizumab would be considered in selected cases assessed by PET-CT and EBV monitoring. Disruption of pembrolizumab treatment may be advisable for the low-risk group(DS 1-2 and EBV not detected), whereas continuation could be warranted for the high-risk group (DS 1-2 and EBV detection, or DS 3-4 and EBV not detected). Moreover, it might be critical to maintain over 24 cycles to improve the survival outcome of R/R ENKTL., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Natural killer/T cell lymphoma (NKTCL) is a highly aggressive, heterogeneous non-Hodgkin lymphoma resulting from malignant proliferation of cytotoxic natural killer (NK) or T cells. Previous studies demonstrated variable expression of CD38 on NKTCL tumors. Daratumumab, a human IgGκ monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action, was hypothesized to be a novel therapeutic option for patients with relapsed or refractory (R/R) NKTCL. In the phase 2 NKT2001 study (ClinicalTrials.gov Identifier: NCT02927925) assessing the safety and efficacy of daratumumab, a suboptimal overall response rate was seen in R/R NKTCL patients. One patient, whose tumors did not express CD38, responded to treatment, suggesting that the immunomodulatory activities of daratumumab may be sufficient to confer clinical benefit. To understand the suboptimal response rate and short duration of response, we investigated the immune profile of NKTCL patients from NKT2001 in the context of daratumumab anti-tumor activity. Tumor tissue and whole blood were, respectively, analyzed for CD38 expression and patient immune landscapes, which were assessed via cytometry by time-of-flight (CyTOF), multiparameter flow cytometry (MPFC), clonal sequencing, and plasma Epstein-Barr virus (EBV)-DNA level measurements. Changes observed in the immune profiles of NKTCL patients from NKT2001, including differences in B and T cell populations between responders and nonresponders, suggest that modulation of the immune environment is crucial for daratumumab anti-tumor activities in NKTCL. In conclusion, these findings highlight that the clinical benefit of daratumumab in NKTCL may be enriched by B/T cell-related biomarkers., (© 2024. The Author(s).)

RE-MIND2 (NCT04697160) compared patient outcomes from the L-MIND (NCT02399085) trial of tafasitamab+lenalidomide with those of patients treated with other therapies for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are autologous stem cell transplant ineligible. We present outcomes data for three pre-specified treatments not assessed in the primary analysis. Data were retrospectively collected from sites in North America, Europe, and the Asia Pacific region. Patients were aged ≥18 years with histologically confirmed DLBCL and received ≥2 systemic therapies for DLBCL (including ≥1 anti-CD20 therapy). Patients enrolled in the observational and L-MIND cohorts were matched using propensity score-based 1:1 nearest-neighbor matching, balanced for six covariates. Tafasitamab+lenalidomide was compared with polatuzumab vedotin+bendamustine+rituximab (pola-BR), rituximab+lenalidomide (R2), and CD19-chimeric antigen receptor T-cell (CAR-T) therapies. The primary endpoint was overall survival (OS). Secondary endpoints included treatment response and progression-free survival. From 200 sites, 3,454 patients were enrolled in the observational cohort. Strictly matched patient pairs consisted of tafasitamab+lenalidomide versus pola-BR (n = 24 pairs), versus R2 (n = 33 pairs), and versus CAR-T therapies (n = 37 pairs). A significant OS benefit was observed with tafasitamab+lenalidomide versus pola-BR (HR: 0.441; p = 0.034) and R2 (HR: 0.435; p = 0.012). Comparable OS was observed in tafasitamab+lenalidomide and CAR-T cohorts (HR: 0.953, p = 0.892). Tafasitamab+lenalidomide appeared to improve survival outcomes versus pola-BR and R2, and comparable outcomes were observed versus CAR-T. Although based on limited patient numbers, these data may help to contextualize emerging therapies for R/R DLBCL. CLINICAL TRIAL REGISTRATION: NCT04697160 (January 6, 2021)., (© 2023. The Author(s).)

Plasmacytoma has been reported to be associated with a poor prognosis in patients with multiple myeloma (MM). In this study, we evaluated the incidence of relapse with plasmacytoma and survival outcomes after upfront autologous stem cell transplantation (ASCT). This study retrospectively analyzed the data of 303 patients with MM who underwent upfront ASCT between April 2000 and April 2018 at eight institutes in the Republic of Korea. In total, 52 patients (17.1%) had plasmacytoma at MM relapse after upfront ASCT, of whom, 27 had paramedullary plasmacytoma (PMD) and 25 had extramedullary plasmacytoma (EMD). Patients with initial plasmacytoma were more likely to have plasmacytoma at MM relapse than those without initial plasmacytoma (37.1% vs. 11.2%). Over a median follow-up of 66.0 months, patients with plasmacytoma at relapse had significantly inferior overall survival (OS) than those without plasmacytoma (43.9 vs. 100.7 months, P < 0.001), but the OS did not significantly differ between patients with EMD and those with PMD (42.2 vs. 56.6 months, P = 0.464). After MM relapse, all patients received salvage therapy, and progression-free survival after relapse was significantly shorter in patients with plasmacytoma than in those without (6.4 vs. 12.4 months, P = 0.007). This study showed that plasmacytoma frequently developed at MM relapse after upfront ASCT in patients with plasmacytoma at the time of diagnosis. Plasmacytoma at relapse was significantly associated with a poor prognosis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We conducted a phase II clinical trial to develop an autologous EBV-specific T cell product (baltaleucel T) for advanced, relapsed ENKTL. Among 47 patients who provided whole blood starting material for manufacturing the product, 15 patients received a median of 4 doses of baltaleucel T. Thirty-two (68%) patients did not receive baltaleucel-T due to manufacturing failure, rapid disease progression, and death. Of the 15 patients, 10 patients had measurable disease at baseline (salvage cohort), and 5 patients had no disease at baseline assessment (adjuvant cohort). In the 15 patients, the median follow-up duration was 10.2 months (range 2.0-23.5 months), median progression-free survival (PFS) was 3.9 months, and the median overall survival (OS) was not reached. Patients in the salvage cohort achieved a 30% complete response (CR) and a 50% overall response rate (ORR). In the adjuvant cohort, disease progression was reported in three patients and two patients did not relapse during study follow-up. When we compared survival outcomes of seven responders and eight non-responders, the PFS (P = 0.001) and OS (P = 0.014) of responders proved statistically superior to that of non-responders. Baltaleucel-T was well tolerated. We have performed a phase II clinical trial of autologous EBV-specific T cell treatment (baltaleucel-T) in R/R ENKTL. Autologous EBV-specific T cells were well tolerated and demonstrated single-agent activity in R/R ENTKL., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The standard of treatment for completely resected limited-stage diffuse large B cell lymphoma (DLBCL) in patients without residual lesions has not yet been established. Previously, we designed a phase II trial to evaluate the safety and efficacy of three cycles of abbreviated R-CHOP in patients with completely resected limited-stage DLBCL and reported favorable survival outcomes. We present the long-term follow-up results to taking into account the importance of delayed relapse in patients with limited-stage DLBCL. With a median follow-up duration of 62.7 months (range, 60.2-75.5 months), the 5-year OS and DFS rates were both 95.0% (95% confidence interval, 85.59-104.11%). Only one patient experienced disease progression which was confirmed at 12.3 months, and one patient with primary intestinal DLBCL developed non-small cell lung cancer 6 years after treatment. The long-term results of our data support the use of three cycles of abbreviated R-CHOP for patients with completely resected limited-stage DLBCL. The study was reviewed and approved by the review boards of the participating institutes and registered at ClinicalTrials.gov , number NCT01279902, in August 3, 2010.

Epstein-Barr virus (EBV) positivity in diffuse large B cell lymphoma (DLBCL) provokes a critical oncogenic mechanism to activate intracellular signaling by LMP1. LMP1 specifically mimics the role of BTK-dependent B cell receptor. Therefore, a trial considering RCHOP therapy along with ibrutinib (I-RCHOP) in combination was conducted among patients with EBV-positive DLBCL. This study was an open-label, single-arm, prospective multicenter phase II clinical trial. Patients received 560 mg of ibrutinib with RCHOP every 3 weeks until 6 cycles were completed or progression or unacceptable toxicity was observed. The primary endpoint was objective response, while secondary endpoints included toxicity, progression-free survival, and overall survival. A matched case-control analysis was completed to compare the efficacy and toxicity of I-RCHOP and RCHOP, respectively, in EBV-positive DLBCL patients. From September 2016 to August 2019, 24 patients proven to have EBV-positive DLBCL in the tissue were enrolled and received I-RCHOP. Their median age was 58 years (range, 28-84 years). The objective overall response was 66.7%, including 16 patients who achieved complete response after 6 cycles. Patients aged younger than 65 years presented a superior OR (87.5%) as compared with those older than 65 years (25.0%; p = 0.01). In a matched case-control study, I-RCHOP therapy provoked a more favorable complete response rate (87.3%) than did RCHOP (68.8%) in those younger than 65 years. Treatment-related mortality was linked most frequently with I-RCHOP therapy (four patients presented with unusual infection without Gr3/4 neutropenia) in the older age group (age ≥ 65 years). In conclusion, in this phase II trial for EBV-positive DLBCL, I-RCHOP was effective but did not show a significant improvement in response and survival in comparison with RCHOP. Also, I-RCHOP promoted serious toxicity and treatment-related death in older patients.

We assessed the efficacy and toxicity of etoposide, methylprednisolone, high-dose cytarabine, and oxaliplatin (ESHAOx) combination chemotherapy in patients with refractory or relapsed Hodgkin's lymphoma (HL). This was an open-label, non-randomized, multi-center phase II study. The ESHAOx regimen consisted of intravenous (i.v.) etoposide 40 mg/m 2 on days 1 to 4, i.v. methylprednisolone 500 mg on days 1 to 5, i.v. cytarabine 2 g/m 2 on day 5, and i.v. oxaliplatin 130 mg/m 2 on day 1. Cycles (up to six) were repeated every 3 weeks. In an effort to identify prognostic markers, the serum levels of cytokines including tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and vascular endothelial growth factor (VEGF) were measured at the time of study entry. A total of 37 patients were enrolled, and 36 were available for evaluation of tumor response. The overall response rate was 72.2% (26/36) (complete response, 33.3% [12/36]; partial response, 38.9% [14/36]). The median time to progression was 34.9 months (95% confidence interval, 23.1-46.7 months). The most common grade 3 or 4 hematological adverse events were neutropenia (16/37, 43.2%), followed by thrombocytopenia (10/37, 27.0%). Grade 3 or 4 non-hematological adverse events were nausea (3/37, 8.1%), anorexia (2/37, 5.4%), mucositis (1/37, 2.7%), and skin rash (1/37, 2.7%). There were no treatment-related deaths. High levels of TNF-α and CRP were significantly associated with poorer overall survival (p = 0.00005 for TNF-α, p = 0.0004 for CRP, respectively). The ESHAOx regimen exhibited antitumor activity and an acceptable safety profile in patients with refractory or relapsed HL. Trial Registration: ClinicalTrials.gov. Registered February 21, 2011, https://clinicaltrials.gov/ct2/show/NCT01300156.

Although lenalidomide plus dexamethasone (RD) is a therapeutic option for relapsed/refractory multiple myeloma (RRMM), limited real-world clinical data exist. The purpose of this study was to estimate efficacy and safety of RD in RRMM patients of the clinical practice. Data from patients at 25 university hospitals in South Korea between October 2009 and December 2016 were collected retrospectively. We report the effectiveness and safety of RD in 546 RRMM patients in routine clinical practice in South Korea. Patients (median age, 65 years) typically received median 7 cycles of RD, and 184 (33.7%) patients were treated with 10 or more cycles of RD. Patients with renal impairment (CLCr < 40 mL/min; 10.4%), comorbid conditions (≥ 2; 12.0%), and poor performance status (≥ 2; 25.1%) were included. The overall response rate was 64.2%: complete response (13.1%), very good partial response (VGPR 19.9%). With median follow-up duration of 18.6 months, median PFS and OS were 11.2 months and 25.2 months, respectively. In multivariate analysis, less than 2 comorbid conditions, normal LDH, failed one chemotherapy prior to RD, and ≥ 10 cycles of RD therapy had significantly prolonged PFS (P = 0.007, P = 0.011, P = 0.007, and P < 0.001, respectively). Adverse events were acceptable. RD is effective and safe in real-life clinical practice, including patients with comorbidities. RD is an effective and safe treatment in a real clinical setting which includes patients with comorbidities. Early and continual use of RD treatment may improve RRMM survival outcomes.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a provisional entity in the 2017 World Health Organization classifications. To further elucidate the clinicopathologic features of this new disease, we carried out a retrospective, multicenter analysis of 42 patients with MEITL. The median age of the patients was 59 years (range, 20-84 years), and 27 patients (64 %) were male. Thirty-two patients (76 %) were Ann-Arbor stages I-II and 28 (67 %) were Lugano stages I-II 1&2 . The most frequent site of involvement was the jejunum (N = 21). Most cases expressed CD8 (79 %) and CD56 (95 %) and did not express CD30 (5 %) or EBER (0 %). The median progression-free survival was 6.9 months (95 % CI 4.3-9.6); the median OS was 14.8 months (2.4-27.2). Thirty-two patients (76 %) underwent surgery and 37 (88 %) received chemotherapy. A complete response (CR) rate was 38 %. Sixteen patients had undergone autologous stem cell transplantation (ASCT). Relapse or progression was documented in 24 cases, most frequently in the primary site (N = 23). Four cases showed central nervous system relapse. Age over 55 years, poor performance scale, advanced Lugano stage (II E -IV), not achieving CR, and not receiving ASCT were associated with inferior OS. While the optimal management of MEITL remains undetermined, achieving CR and consolidative ASCT seem essential. As CHOP might be insufficient for achieving CR, more efficient combinations should be investigated. Additionally, considering the frequent local failure and CNS relapse, novel therapeutic approaches are required to improve survival.

Primary central nervous system lymphoma (PCNSL) is a rare extranodal non-Hodgkin lymphoma for which standard treatment has yet to be established. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a suitable consolidation strategy for patients who respond to induction chemotherapy. The purpose of this study was to compare the outcome and toxicity profile of the combination of busulfan, cyclophosphamide, and etoposide (BuCyE) with that of the combination of thiotepa, busulfan, and cyclophosphamide (TBC) as conditioning regimens of upfront ASCT for consolidation therapy in PCNSL. The PCNSL registry data set, prospectively collected from March 1993 to May 2017 at Asan Medical Center, was reviewed retrospectively. Patients with objective response to induction chemotherapy who received BuCyE or TBC as conditioning regimen for ASCT were included in the analysis. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Among 241 patients with a diagnosis of PCNSL, 53 received ASCT as upfront consolidation therapy with TBC (28 patients) or BuCyE (25 patients) as conditioning regimen. No median OS or PFS was reached in the TBC group, while the BuCyE group reached a median OS of 4.9 years (p = 0.02) and median PFS of 1.1 years (p = 0.007). The incidence of oral mucositis, nausea, and vomiting was higher with TBC than BuCyE. The median admission duration and days to engraftment were similar between the two groups. Despite the greater incidence of adverse events, TBC showed better outcomes than BuCyE in terms of survival.

Cell-of-origin (COO) classification of diffuse large B cell lymphoma (DLBCL) is increasingly important due to its prognostic significance and the development of subtype-specific therapeutics. We compared the clinical utility of the Lymph2Cx assay against four widely used immunohistochemical algorithms in 150 R-CHOP-treated DLBCL patients using archival tissue. In contrast to the predominance of germinal center B cell-like (GCB) subtype in Western populations, Lymph2Cx assay classified more than half of the Korean cases as the activated B cell-like (ABC) subtype (ABC, 83/150 [55.3%]; GCB, 51/150 [34.0%]; unclassifiable, 16/150 [10.7%]). Predominance of ABC subtype tended to be more pronounced in the nodal lymphomas than in the extranodal lymphomas. However, among the primary extranodal sites, ABC subgroups predominated in primary testicular, breast, and adrenal gland lymphomas. The classification of COO by Lymph2Cx assay did not show any significant association with clinical parameters. The overall concordance rates of the immunohistochemical algorithms with the Lymph2Cx ranged from 78.0 to 84.3%. However, 47.1-66.7% of the cases of the Lymph2Cx-defined GCB subgroup were misclassified as the non-GCB class by the IHC algorithms. The survival of Lymph2Cx-classified COO subtypes was not significantly different in the present cohort. In conclusion, ABC subtype predominated over GCB in Korean patients. There are significant discrepancies between the immunohistochemistry and Lymph2Cx classifications, especially in GCB subtype.

Both-side synchronous involvement has been reported to account for 7-24% of ocular adnexal marginal zone lymphoma (OAML). We conducted a retrospective analysis to identify the clinical features and treatment outcomes of synchronous bilateral OAML (SB-OAML) by treatment modality. We analyzed patients with a histologic diagnosis of SB-OAML, excluding metachronous bilateral involved OAML. We enrolled a total of 95 patients for this analysis, 36 males and 59 females; the median patient age was 42 years (range 16-77 years). Eleven (11.6%) patients had been treated with chemotherapy or chemo-immunotherapy (eight R-CVP, two CVP, and one R-CHOP). The median number of treatments was 6 (range 6-8); there were 9 complete responses (CRs; 81.8%) and 2 partial responses (PRs; 18.2%). Nearly all patients (88.4%) received radiotherapy in both eyes, and the median radiation dose was 27 Gy (range 20-40 Gy) to each eye; 68 CRs (80.9%) and 14 PRs (16.7%) were achieved. Ten-year progression-free survival (PFS) and overall survival (OS) rates were 79.8 and 91.1%, respectively. Radiotherapy continued to be an independent prognostic marker, with the hazard of progression (P = 0.036). Eleven patients (13.1%) had surgery for cataract treatment during follow-up, and patients who received low-dose radiation (< 30.3 Gy) experienced fewer cataract operations. SB-OAML was predominantly observed in young females, and they had good response and prognosis regardless of treatment modalities. Low-dose radiotherapy to both eyes showed a tendency of longer PFS than did chemotherapy and could decrease cataract operations.

Bendamustine plus rituximab (BR) showed efficacy and safety in indolent lymphomas and mantle cell lymphoma. However, there were limited experiences of real-world practice of BR in diffuse large B cell lymphoma (DLBCL). In this study, we report the Korean experiences with BR in relapsed or refractory DLBCL who are not eligible for intensive chemotherapy and autologous stem cell transplantation. This is an observational, multicenter, retrospective analysis. Between December 2011 and December 2015, a total of 58 patients with relapsed or refractory DLBCL were treated with BR in 11 tertiary hospitals in Korea. Patients received an intravenous (IV) infusion of rituximab at a dose of 375 mg/m 2 on day 1. On days 2 and 3, patients received an IV infusion of bendamustine at doses of 120 or 90 mg/m 2 . Median age was 69 (range 18-86), 74.1% had stage III or IV disease, and 67.2% showed high-intermediate or high International Prognostic Index scores at diagnosis. In an intention-to-treat analysis, 18 patients (31.0%) showed a complete response and 14 (24.1%) showed a partial response, resulting in an overall response rate of 55.1%. The median duration of the response was 3.7 months (range 1.0-47.2 months). The median progression-free survival was 3.9 months (95% confidence interval [CI], 2.4-5.4 months), and the median overall survival was 6.7 months (95% CI, 4.7-8.7 months). The most common grade 3/4 adverse event was neutropenia (n = 40; 68.9%). Febrile neutropenia was observed in 11 patients (18.9%). Grade 3/4 thrombocytopenia was observed in 34 patients (58.6%). Our study confirmed the high efficacy and acceptable toxicity profile of BR in relapsed or refractory DLBCL patients. However, we need to closely observe the higher tendency of grade 3/4 hematological toxicities in Korean patients.

Recent studies have reported the associations between programmed death-ligand 1 (PD-L1) or PD-L2/PD-1 pathways and pro-angiogenic genes including hypoxia-inducible factors (HIFs) and vascular endothelial growth factor (VEGF) in several malignancies. However, no study has examined the relationship or prognostic implication of PD-L1, PD-L2, PD-1, VEGF expression, and microvessel density (MVD) in classical Hodgkin lymphoma (cHL) patients. Diagnostic tissues from 109 patients with doxorubicin, bleomycin, vinblastine, and dacarbazine-treated cHL were evaluated retrospectively by immunohistochemical analysis for PD-L1, PD-L2, PD-1, VEGF expression, and for CD31 expression as a measure of MVD. There was a positive correlation between PD-L1 and VEGF expression (P = 0.008) and additionally between PD-L2 and VEGF expression (P = 0.001). The mean MVD in tumors positive for both PD-L1 and VEGF was significantly (P = 0.022) higher than the mean MVD in tumors negative for both markers. High PD-1 expression group had lower (P = 0.019) 5-year overall survival rate than low PD-1 expression group. Multivariate analysis revealed that PD-1 was an independent prognostic factor for cHL with significance (P = 0.026). However, PD-L1, PD-L2, and VEGF expression had no prognostic impact. Our data confirmed the positive correlations between PD-L1, VEGF, or MVD. Our findings provided evidence supporting new therapeutic approaches including combinations of anti-PD-L1/PD-1 and anti-VEGF therapy in addition to the current standard regimen for cHL.

18 F-fluoro-2-dexoy-D-glucose-positron emission tomography (PET)/computed tomography (CT) is a useful imaging technique for monitoring the treatment response in lymphoma cases. We investigated the value of interim brain PET/CT (I-PET/CT) for monitoring the response to intensive methotrexate-based chemotherapy in primary central nervous system lymphoma (PCNSL) patients with diffuse large B cell lymphoma (DLBCL). Of the 76 PCNSL patients treated with intensive methotrexate and cytarabine chemotherapy between September 2006 and December 2012, 66 patients with DLBCL were included in this study. The patient cohort of 66 individuals comprised 43 men and 23 women with a median age of 59 years (range, 17-75 years). During chemotherapy, 36 patients (54.5%) showed a negative metabolism on I-PET/CT, and 47 (71.2%) were negative on final (F) PET/CT. The baseline characteristics were similar between I-PET/CT-negative (n = 36) and I-PET/CT-positive patients (n = 30) except ECOG performance status. After a median follow-up of 27.5 months, there was no difference in the progression-free survival (PFS; P = 0.701) or overall survival (OS; P = 0.620) between the I-PET/CT-negative and I-PET/CT-positive groups. However, PFS in the F-PET/CT-negative group was significantly longer than that in the F-PET/CT-positive group (P < 0.001) without a significant difference in OS (P = 0.892). I-PET/CT may not predict the survival outcome of PCNSL patients with DLBCL treated with intensive methotrexate and cytarabine chemotherapy. Prospective trials are required to fully evaluate the role of I-PET/CT.

The objective of this study was to examine the prevalence and factors associated with sexual problems and their relationship to health-related quality of life (HRQOL) in male and female non-Hodgkin lymphoma (NHL) survivors. In this cross-sectional study, 738 NHL survivors (425 men and 313 women; mean time since diagnosis, 6.2 years) in South Korea completed the six-item instrument of adult sexual behavior used by the National Health and Social Life Survey in the United States. HRQOL was measured by two subscales of the EORTC QLQ-C30. Sexual problems were reported by a greater proportion of women (range, 31.9 to 64.4%) than men (range, 23.3 to 49.1%). Among four items common to both sexes, three (lacking interest in sex, unable to achieve orgasm, sex not pleasurable) were significantly more prevalent in women. Significant factors associated with multiple sexual problems in men were older age and being unemployed; in women, they were marital status and comorbidity. Lastly, more significant associations between sexual problems and HRQOL were observed in men than in women. Male and female NHL survivors differ in the prevalence of sexual problems and the factors associated with them as well as their associations with HRQOL. These findings can be used to develop sex-specific interventions to improve sexual function in this population.

Extranodal involvement is a well-known prognostic factor in patients with diffuse large B-cell lymphomas (DLBCL). Nevertheless, the prognostic impact of the extranodal scoring system included in the conventional international prognostic index (IPI) has been questioned in an era where rituximab treatment has become widespread. We investigated the prognostic impacts of individual sites of extranodal involvement in 761 patients with DLBCL who received rituximab-based chemoimmunotherapy. Subsequently, we established a new extranodal scoring system based on extranodal sites, showing significant prognostic correlation, and compared this system with conventional scoring systems, such as the IPI and the National Comprehensive Cancer Network-IPI (NCCN-IPI). An internal validation procedure, using bootstrapped samples, was also performed for both univariate and multivariate models. Using multivariate analysis with a backward variable selection, we found nine extranodal sites (the liver, lung, spleen, central nervous system, bone marrow, kidney, skin, adrenal glands, and peritoneum) that remained significant for use in the final model. Our newly established extranodal scoring system, based on these sites, was better correlated with patient survival than standard scoring systems, such as the IPI and the NCCN-IPI. Internal validation by bootstrapping demonstrated an improvement in model performance of our modified extranodal scoring system. Our new extranodal scoring system, based on the prognostically relevant sites, may improve the performance of conventional prognostic models of DLBCL in the rituximab era and warrants further external validation using large study populations.

In real clinical settings (not clinical trials), thalidomide has been accepted as maintenance therapy to patients with multiple myeloma (MM) because of the cost of drugs, the limitations of medical insurance, etc., in our country (South Korea). The purpose of this study was to evaluate the utility of thalidomide maintenance for improving survival in transplantation-eligible patients with MM in the real clinical field. Differences in survival rates were estimated in patients treated with or without thalidomide maintenance. The 3-year progression-free survival rates (PFS) of patients with and without maintenance, respectively, were 55.4 and 37.2 % (p = 0.005). The 3-year overall survival rates (OS) were 88.0 and 84.0 % (p = 0.105). No difference in 3-year OS after relapse or progression (OS2) was observed between the two groups (50.4 and 55.3 %, p = 0.661). The 3-year PFS of patients with and without maintenance therapy who had shown less than CR after ASCT were 68.4 and 23.3 % (p < 0.001). In conclusion, Thalidomide maintenance therapy showed longer PFS in real clinical practice, and long-term use of thalidomide did not interfere with the efficacy of salvage chemotherapy in patients who experienced progression or relapse after ASCT. In addition, thalidomide maintenance might be also useful for patients who have shown less than CR after ASCT.

Purpose: Mantle cell lymphoma (MCL) is a disease that frequently relapses and primarily affects elderly people. We performed an open-label, multi-center, phase II study to investigate the effect and quality of life (QoL) of treatment with vorinostat in combination with fludarabine, mitoxantrone and dexamethasone (V-FND) for relapsed or refractory MCL., Methods: The treatment schedule was composed of four cycles of induction treatment with V-FND and subsequent consolidation therapy involving autologous hematopoietic stem cell transplantation or six cycles of vorinostat maintenance. QoL was assessed using EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) every 2 cycles., Results: Data from a total of 20 patients were collected for an interim analysis. The median age was 67 years (range 49-75), and 14 or the patients (70 %) were male. The full course of V-FND induction treatment was completed in 11 patients, but only three completed all six cycles of maintenance therapy. Response to V-FND was not available in two patients. Among the other 18 patients, the objective response rate was 77.8 % (complete response in five patients + partial response in nine patients). Median progression-free survival was 9.3 months [95 % confidence interval (CI) 4.0-12.3]. Fifteen patients (75 %) experienced grade 3/4 toxicities. Analysis of QoL demonstrated significant deterioration of social functioning (p = 0.01), and significant aggravation of fatigue and nausea/vomiting (p = 0.04 and 0.01, respectively) after two cycles of V-FND induction., Conclusions: V-FND is effective in patients with relapsed or refractory MCL. However, significant toxicities were hurdles to sustained V-FND therapy.

Epstein-Barr virus (EBV) in the peripheral blood has become a significant predictor of clinical outcomes in EBV-associated Hodgkin lymphoma (HL). However, due to its relative rarity, prevalence and prognostic role of circulating EBV-DNA has not been well established in Asian patients. Seventy patients with newly diagnosed HL were prospectively registered between October 2007 and January 2013, and underwent pretreatment whole blood (WB) EBV-DNA quantitation using real-time polymerase chain reaction (RT-PCR). WB EBV-DNA in baseline and serial RT-PCR within 1 year were investigated. Clinicopathologic parameters of the patients according to pretreatment WB EBV-DNA were also explored. Twelve patients (17.1 %) demonstrated WB EBV-DNA(+), which was significantly associated to older age, advanced stages, frequent involvements of extranodal sites, low serum albumin and hemoglobin levels, and high international prognostic scores ≥2. Three-year event-free survival (EFS) and overall survival (OS) were significantly inferior in patients with pretreatment WB EBV-DNA(+) (53.5 vs 67.0 and 65.6 vs 90.2 %) (p < 0.032 and <0.01). Negatively conversed EBV-DNA within 1 year after chemotherapy also significantly affected favorable EFS (p < 0.01). Taken together, pretreatment WB EBV-DNA(+) may be a significant predictor of inferior EFS and OS over EBV-encoded RNA in situ hybridization (EBER-ISH)(+) in Korean patients with HL. Serial EBV-DNA monitoring following chemotherapy also seems helpful to predict survival outcomes.

Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) has been shown to improve the rates of successful peripheral blood stem cell (PBSC) mobilization in patients with malignant lymphoma or multiple myeloma (MM) who experienced prior failure of PBSC mobilization. We evaluated the mobilization results of re-mobilization using plerixafor and G-CSF in insufficiently mobilizing patients. Forty-four patients with lymphoma (n = 29) or MM (n = 15) were included in the study. The median age was 50 (range, 24-64) years. Previous mobilization regimens were chemotherapy with G-CSF (n = 28), including cyclophosphamide with G-CSF (n = 15), and G-CSF only (n = 16). All patients with lymphoma achieved at least partial response (PR) before the mobilization, including 13 complete responses (CRs). Eleven patients with MM achieved at least PR and four patients with MM were in stable disease before mobilization. The median number of apheresis was 3 (range, 1-6). The median yield of PBSC collections was 3.41 (0.13-38.11) × 10(6) CD34(+) cells/kg. Thirty-four (77.3 %) patients had successful collections defined as at least 2 × 10(6) CD34(+) cells/kg. The rate of successful collections was not different between the two underlying diseases (79.3 % in lymphoma and 73.3 % in MM). Of the entire cohort, 38 (86.4 %) of patients went on to receive an autologous transplant. Previous long-term use of high-risk drugs (>4 cycles use of alkylating agents, platinum-containing agents, or thalidomide) (HR 10.8, 95 % CI 1.1-110.0, P = 0.043) and low platelet count (<100 × 10(9)/L) 1 day before the first apheresis (HR 27.9, 95 % CI 2.9-273.7, P = 0.004) were independent prognostic factors for predicting failure of PBSC re-mobilization using plerixafor and G-CSF. In conclusion, re-mobilization using plerixafor and G-CSF showed a success rate of 77.3 % in patients with lymphoma or MM who experienced prior failure of PBSC mobilization, and the majority of them underwent autologous transplant. Therefore, plerixafor-based re-mobilization was an effective method in poor mobilizers.

Obesity was recently reported to confer a survival advantage in diffuse large B cell lymphoma (DLBCL) among Western populations. Given ethnic differences, previous studies recommended a revision of the WHO classification of obesity for Asians. We investigated the prognostic impact of body mass index (BMI) using modified WHO criteria in a retrospective cohort of 562 Korean patients with DLBCL. Patients were categorized into five groups according to BMI: 26 (4.6 %) as underweight (<18.5 kg/m(2)), 230 (40.9 %) as normal weight (18.5-22.9 kg/m(2)), 129 (23.0 %) as overweight (23.0-24.9 kg/m(2)), 160 (28.5 %) as obese (25.0-29.9 kg/m(2)), and 17 (3.0 %) as severely obese (≥30 kg/m(2)). As BMI increased, the relative hazard ratio (HR) decreased sharply, reaching the lowest value in the overweight group, and then rose again in the obese and severely obese. On univariate analysis, both overall survival (OS) and progression-free survival (PFS) were best in the overweight group, followed by normal > obese > severely obese > underweight groups. Multivariate analysis showed a significantly shorter survival in the underweight (OS: HR 2.90, 95 % confidence interval (CI) 1.35-6.19, P = 0.006; PFS: HR 3.08, 95 % CI 1.55-6.09, P = 0.001) and severely obese groups (OS: HR 2.93, 95 % CI 1.08-7.95, P = 0.035; PFS: HR 2.59, 95 % CI 1.06-6.36, P = 0.038). We show that being underweight or, contrary to findings in Western patients, being severely obese has a deleterious prognostic impact in DLBCL in Koreans. Revising the BMI criterion that defines obesity according to the patient's ethnic differences could therefore better delineate DLBCL risk groups in Asian patients.

Purpose: The role of non-surgical treatments (NS), such as chemoradiotherapy or radiotherapy, for clinical T1N0M0 esophageal cancer (cT1N0M0 EC) has not been well delineated. The aim of this study was to evaluate and compare the feasibility and efficacy of NS and Surgical treatment (S) in cT1N0M0 EC patients., Methods: The medical records of patients who received treatment for cT1N0M0 EC at Asan Medical Center between 2003 and 2012 were retrospectively reviewed. The baseline characteristics, treatment outcomes and complications, and survival were compared., Results: There were 264 S and 20 NS patients with respective median ages of 69.5 and 63.0. The main histologic finding was squamous cell carcinoma in both groups (97 and 100 %, respectively). The Eastern Cooperative Oncology Group performance status and Charlson comorbidity index score were poorer in the NS group. With a median follow-up of 49.0 months, 37 S patients (14 %) and 3 NS patients (15 %) exhibited recurrence. The first sites of recurrence for S and NS patients were locoregional (21 vs. 3 patients), distant (6 vs. 0), and both locoregional and distant (9 vs. 0), respectively. The median time-to-recurrence could not be calculated in either group (log-rank test P = 0.831). The estimated median overall survival was 64.4 months (95 % CI 37.2-91.6 months) in the NS group and could not be calculated in the S group (P = 0.056)., Conclusions: Non-surgical treatments can be an effective alternative to S for patients with cT1N0M0 EC unfit for radical surgery. The role of NS for early stage EC needs to be further verified with prospective randomized trials.

We conducted a phase II trial of concurrent chemoradiotherapy (CCRT) followed by 2 cycles of L-asparaginase-containing chemotherapy for patients who were newly diagnosed with stages IE and IIE nasal extranodal NK/T cell lymphoma (ENKTL). CCRT consisted of 40-44 Gy of radiotherapy with weekly administration of 30 mg/m(2) of cisplatin for 4 weeks. Two cycles of VIDL (etoposide (100 mg/m(2)), ifosfamide (1,200 mg/m(2)), and dexamethasone (40 mg) from days 1 to 3, and L-asparaginase (4,000 IU/m(2)) every other day from days 8 to 20) were administered sequentially. CCRT yielded a 90 % overall response rate without significant side effects in 30 patients, including 20 patients with complete response (CR); however, two patients showed distant disease progression. After CCRT, VIDL chemotherapy showed an 87 % final CR rate (26/30). Although grade III or IV hematologic toxicity was frequent during VIDL chemotherapy, no treatment-related mortality was observed, and L-asparaginase-associated toxicity was manageable. With a median follow-up of 44 months, 11 patients showed local (n = 4) and distant (n = 7) relapse or progression. The estimated 5-year progression-free and overall survival rates were 73 and 60 %, respectively. In conclusion, CCRT followed by L-asparaginase-containing chemotherapy is a feasible treatment for newly diagnosed stages IE/IIE nasal ENKTL.

Although serum beta-2 microglobulin (B2M) has been suggested as an independent prognostic factor for several lymphoproliferative diseases, it has rarely been investigated in extranodal natural killer/T cell lymphoma (ENKTL). From a prospectively collected database, 145 patients with ENKTL were identified. Among them, a total of 101 patients were included in the analysis, with exclusion of patients without baseline serum B2M level and those did not receive anticancer therapy. Serum B2M (<3.0 vs. ≥3.0 mg/L) was analyzed for association with overall survival (OS). Seventy-nine (78 %) patients had nasal ENKTL, and 22 (22 %) had extranasal ENKTL. In overall patients, median OS was 26.7 months (95 % confidence interval (CI), not assessable), with a median follow-up of 32.4 months (range, 0.9-155.2 months). While median OS was not reached in patients with nasal ENKTL, extranasal ENKTL group had median OS of 5.1 months (95 % CI, 1.2-8.9 months; p < 0.001). Baseline serum B2M was significantly associated with OS in patients with nasal ENKTL (p < 0.001). This was consistent in limited (stages I and II) nasal ENKTL (p = 0.002) and disseminated (stages III and IV) nasal ENKTL (p = 0.02). However, there was no difference of OS in extranasal ENKTL patients (p = 0.69). In multivariate analysis including other prognostic factors, elevated serum B2M was significantly associated with poor OS (hazard ratio (HR) = 3.8, 95 % CI 1.7-8.2, p = 0.001, in a model including Korean Prognostic Index, and HR = 3.6, 95 % CI 1.6-8.2, p = 0.002, in a model including International Prognostic Index). In patients with nasal ENKTL, baseline serum B2M is a powerful prognostic factor. The prognostic value of B2M was independent of previously established prognostic models. Further investigations are necessary to validate the role of B2M in ENKTL.

Multiple myeloma (MM) is characterized by clonal expansion of malignant bone marrow cells producing a unique monoclonal immunoglobulin. The appearance of abnormal protein band (APB) in MM has been reported during follow-up. We aimed to evaluate the clinical characteristics and outcomes of patients with APB in a single center cohort. A total of 377 consecutive MM patients were treated at the Asan Medical Center between January 2002 and December 2012. We compared clinical characteristics and survival outcome between those with and without APB. Of the 377 patients, 34 (9 %) experienced APB. They comprised 18.2 % (27/148) of patients treated with autologous stem cell transplantation (ASCT) and 3.1 % (7/229) of those not receiving ASCT. APB occurred after a median of 7.9 months (range, 2.2-95.7 months) from diagnosis. Immunoglobulin isotypes at diagnosis were as follows: IgG (n = 10), IgA (n = 8), IgD (n = 5), free κ (n = 4), and free λ (n = 7). Nine patients experienced a second APB. With a median follow-up of 54.1 months, the median overall survival (OS) has not been reached in patients with APB and was 38.3 months in patients without (P < 0.001). Multivariate analysis indicated that the development of APB was a significant favorable prognostic factor for OS (hazard ratio 0.21; 95 % confidence interval 0.08-0.52). Serum β₂-microglobulin, albumin, creatinine, and ASCT were also independent prognostic factors for OS. Further investigation is required to establish the mechanisms underlying APB in MM.

Hodgkin lymphoma (HL) in resource-poor population shows an early childhood peak with predominance of mixed cellularity (MCHL) and high Epstein-Barr virus (EBV) association, whereas HL in resource-rich population has a peak in ages 15-29 years with the predominance of nodular sclerosis (NSHL) and low EBV association. We examined the changing trend of HL in association with EBV in Korea in 385 cases of HL (1980-2011). Data from 1980-1995 and 1996-2011 were compared. Age distribution showed a marked decrease in children (age < 15 years) (21.0 % to 8.6 %, p = 0.004) and sharp increase in young adults (ages 15-29 years) and ages 30-59 years. Male predominance decreased from 3.04 to 1.57. Predominant subtype changed from MCHL to NSHL; MCHL fell from 53.3 % to 26.4 % (p < 0.001), and NSHL rose from 24.8 % to 58.2 % (p < 0.001). EBV-positive HL decreased from 66.7 % to 38.2 %. However, in young adult females, EBV positive cases increased, contributing to the peak in this age group. Epidemiology of HL in Korea is rapidly changing into a Western pattern concurrent with the socioeconomic changes. Analysis of the cases stratified by EBV status and sex identified a smaller hidden peak in the young adult age, which confirms the four disease hypothesis proposed by Jarrett. We propose EBV testing as an essential component in epidemiologic study of Hodgkin lymphoma.

Although a few studies have evaluated the utility of ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) in treatment-naive T-cell non-Hodgkin's lymphomas (T-NHLs), a few studies had been conducted to evaluate the role of FDG-PET in patients after treatment. A total of 41 patients with T-NHLs were included who underwent post-autologous stem cell transplantation (ASCT) PET for response assessment in addition to contrast-enhanced CT. The impact of post-ASCT PET on response assessment and predicting prognosis was retrospectively evaluated. Of the 41 patients, 11 (26.8%) patients showed discordant response between two image modalities (Cohen's κ = 0.465). The additional PET study actually guides changing the post-ASCT response in six (54.5%) of these 11 patients. Moreover, positive post-ASCT PET was associated with worse prognosis in event-free survival and overall survival than negative post-ASCT PET (P = 0.003 and P = 0.044, respectively). Excluding four patients in whom further confirmation was not available due to early mortality, in 22 lesions showing discrepancy between two image modalities, 12 lesions were true positive (N = 4) or true negative (N = 8) for PET and ten lesions were false positive (N = 7) or false negative (N = 3). The accuracy for the discrepant lesions was 54.5% (12 of 22), the overall accuracy for the detected lesions was 76.7% (33 of 43), and the overall accuracy for patients was 89.2% (33 of 37). Post-ASCT PET was useful in response assessment after ASCT, and the positive post-ASCT PET result was associated with worse prognosis than the negative post-ASCT PET in patients with T-NHLs.

Purpose: We conducted a prospective observational study for premenopausal women receiving adjuvant adriamycin and cyclophosphamide-containing regimens to define the pattern of chemotherapy-induced amenorrhea (CIA), the menopause-specific quality of life (MENQOL), and the hormone profiles., Methods: From October 2003 to July 2007, 387 patients with breast cancer who underwent curative surgery were prospectively included. Patient self-assessment by MENQOL questionnaires and blood samples for hormone assays were taken before chemotherapy, and 1, 6, and 12 months after chemotherapy was completed., Results: Patients were categorized into three groups according to their duration and reversibility of amenorrhea, with 312 eligible patients split into long-term CIA (n = 180, 57.7 %), temporary CIA (n = 113, 36.2 %), and menstrual irregularity (n = 19, 6.1 %) groups. Risk factors for long-term CIA were identified as age ≥40 years (p < 0.001), the addition of taxane (p = 0.01), and tamoxifen use (p = 0.03). MENQOL was worst immediately after the completion of adjuvant chemotherapy, and this was not fully recovered even 12 months after chemotherapy had finished. Age ≥40 years and tamoxifen exposure were inversely associated with MENQOL. In long-term CIA patients, the level of follicle-stimulating hormone increased after chemotherapy; this level, however, was reduced in patients who received tamoxifen, but remained high and stable in those who did not (p < 0.001 at 6 months; p < 0.001 at 12 months)., Conclusion: This study showed that most premenopausal breast cancer patients who received adjuvant chemotherapy experienced clinically significant CIA, followed by impaired MENQOL. Our findings may be relevant in the decision-making processes for premenopausal women with breast cancer.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive hematologic malignancy originating from the precursor of the plasmacytoid dendritic cell. It is very rare and has only recently been recognized as a distinct entity. In this study, we report our experience of BPDCN to review the clinical, pathological features and treatment outcomes. A database at the Asan Medical Center was screened for all patients with BPDCN treated between 2000 and 2010. Seven patients were confirmed as BPDCN and included in this analysis. The median age of the patients was 40 years (range, 18-62 years), and four patients were male. Sites of disease involvement included the skin (n = 4), lymph node (n = 4), and peripheral blood/bone marrow (n = 2). Tumor cells were positive for CD4 (n = 5), CD56 (n = 6), and CD123 (n = 7). Six patients received multi-agent chemotherapy as first-line treatment, while one patient was given radiotherapy. The median progression-free survival was 8.6 months (range, 2.6-28.9 months) and overall survival was 15.1 months (range, 4.4-60.0 months) with a median follow-up period of 13.8 months (range, 1.9-29.9 months). Notably, all four patients with cutaneous involvement survived, whereas those without skin involvement succumbed to death, even though two of them were given salvage chemotherapy. In this study, patients with BPDCN showed various clinical, histological, and immunophenotypical features. Our experience warrants further examination of the prognostic significance of skin involvement in BPDCN.

R-CHOP chemotherapy composed of rituximab, cyclophosphamide, adriamycin, vincristine, and prednisolone which might increase the risk of Pneumocystis pneumonia in patients with non-Hodgkin lymphoma. We estimated the point prevalence of Pneumocystis pneumonia in non-Hodgkin lymphoma patients according to the number of R-CHOP cycles and investigated whether cytoreduction by chemotherapy is associated with Pneumocystis pneumonia development. We retrospectively established a cohort of patients who received R-CHOP for non-Hodgkin lymphoma in our institution. Using this cohort, we estimated the incidence rate and point prevalence of definite and probable Pneumocystis pneumonia. To assess factors associated with Pneumocystis pneumonia development several clinical variables, including absolute neutrophil and lymphocyte count at the time of non-Hodgkin lymphoma diagnosis and when the last R-CHOP cycle was administered, were compared between patients with and without Pneumocystis pneumonia. Of 713 patients in the cohort, 14 and 18 patients were diagnosed with definite and probable Pneumocystis pneumonia, respectively. The overall incidence of definite and definite plus probable PCP in NHL patients receiving R-CHOP were 2.0 % (14/713; 95 % CI, 1.1-3.3 %) and 4.5 % (32/713; 95 % CI, 3.2-6.4 %), respectively. This corresponded to 3.8 (95 % CI, 2.2-6.4) and 8.4 (95 % CI, 5.9-11.9) per 1000 persons. Many cases of Pneumocystis pneumonia (22/32, 68.7 %) developed after administration of the fourth R-CHOP cycle. However, there was no statistical difference in Pneumocystis pneumonia prevalence between patients receiving four or more cycles of R-CHOP and fewer than. Higher absolute neutrophil count (4,742/mm(3) vs. 2,627/mm(3); p < 0.01) was associated with Pneumocystis pneumonia development at the last R-CHOP cycle, while absolute lymphocyte count at the time of NHL diagnosis was not. Contrary to expectations, Pneumocystis pneumonia is not a frequent complication of R-CHOP treatment for non-Hodgkin lymphoma. Cytoreduction of R-CHOP might not be a risk factor of Pneumocystis pneumonia development. Universal prophylaxis against Pneumocystis pneumonia during R-CHOP treatment could not be strongly recommended.

Extranodal involvement is common in patients with Burkitt lymphoma (BL). We evaluated the pattern of extranodal involvement and its impact on clinical outcomes in a single center cohort of adult Korean patients with sporadic BL. We retrospectively identified 64 patients with BL in the registry of non-Hodgkin lymphoma of the Asan Medical Center between 1996 and 2009. We assessed their clinical features and distribution of extranodal sites and analyzed clinical outcomes, including complete response rate after chemotherapy, overall survival, and progression-free survival, relative to baseline characteristics and involved extranodal sites. Extranodal involvement was found in 57 patients (89 %), with 34 (53.1 %) having two or more extranodal sites. The stomach (26.6 %) was the most common site, followed by the small and large intestines (25 %), bone marrow (23.4 %), genitourinary tract (21.9 %), and bones (18.8 %). Two patients (3.1 %) showed central nervous system (CNS) involvement. Complete response rates to chemotherapy were not related to sites of extranodal involvement. Two-year overall survival rates were lower in patients with bone marrow (33.3 vs. 74.6 %, p = 0.010) and CNS (0.0 vs. 66.6 %, p = 0.048) involvement than in patients with involvement at other extranodal sites. The stomach, genitourinary tract, and bones were the most commonly involved extranodal sites in Korean BL patients, but site had no prognostic significance.

The combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) plus rituximab is the standard treatment for patients with primary gastric diffuse large B cell lymphoma (DLBCL). However, a few trials comparing CHOP plus rituximab (R-CHOP) with CHOP have been conducted in primary gastric DLBCL. Among 93 consecutive patients receiving CHOP or R-CHOP as a first-line chemotherapy at our institution, 38 patients received CHOP and 55 patients received R-CHOP. With a median follow-up time of 48 months, the complete response (CR) rate, event-free survival (EFS), and overall survival (OS) did not differ between two treatment groups (P = 1.000, P = 0.744, and P = 0.213, respectively). The CR rates were 93.9% for patients receiving CHOP and 92.5% for patients receiving R-CHOP. The 3-year EFS rates were 86.0% for patients receiving CHOP and 81.7% for patients receiving R-CHOP; the 3-year OS rates were 94.7 and 84.7%, respectively. In a multivariate analysis, The CR rate was affected by the number of extranodal involvements (P = 0.011). The EFS and OS rates were affected by the Lugano stage (P = 0.067 and P = 0.008, respectively). High serum level of β₂-microglobulin was associated with worse EFS and OS in patients receiving R-CHOP (P = 0.018 and P = 0.015, respectively). In conclusion, the addition of rituximab was not found to have an impact on patients' outcomes with primary gastric DLBCL. The β₂-microglobulin in primary gastric DLBCL might be able to discriminate the patients' prognosis who are treated with R-CHOP chemotherapy.

Epstein-Barr virus (EBV) is considered a prognostic marker in Hodgkin lymphoma (HL) patients, but previous studies have yielded mixed findings because of the confounding effects of factors including age. We examined the prognostic impact of EBV status on 159 patients with HL. The median age at diagnosis was 32 years (range, 4-77 years). The median follow-up time was 5.83 years (range, 0.33-19.69 years). Tumor cell EBV status was positive in 34.5 %. EBV-positive HL was associated with age of ≥ 25 years, male gender, B symptoms, advanced stage, high-risk IPS, nonnodular sclerosis subtype, and treatment with chemotherapy only (P < 0.05). The 5-year disease-specific survival (DSS) rates were 94.1 and 76.4 % for the EBV-negative and EBV-positive HL, respectively, (P < 0.001). On univariate analysis, event-free survival, DSS, and overall survival (OS) were significantly associated with age 40 years or older, B symptoms, and high-risk international prognostic score (≥ 4). On multivariate analysis, EBV positivity was found to be a significant prognostic factor for DSS, particularly in adults 25 years or older. Subgroup analysis showed significant association of EBV-positive HL with poorer DSS and OS in adults 25 years or older with advanced stage disease. In the present series of HL patients, the presence of EBV in tumor cells is associated with adverse prognostic factors. EBV-positive HL is significantly associated with poorer DSS in all age groups.

Background: Inter-individual variability of pharmacokinetics may account for unpredictable toxicities of docetaxel., Methods: From March 2007 to June 2008, female patients with operable lymph node-positive breast cancer receiving docetaxel-containing adjuvant chemotherapy were included in this study. The 4 cycles of planned dose of docetaxel (100 mg/m(2)) was performed as adjuvant chemotherapy, following 4 cycles of adriamycin and cyclophosphamide. We evaluated toxicity profile of docetaxel and single nucleotide polymorphisms (SNPs) of CYP3A5 gene, ABCB1 gene, ABCC2 gene and SCLO1B3 gene. Toxicities during treatment of docetaxel were evaluated and defined according to the NCI CTCAE version 3.0., Results: Pharmacogenetic analysis was performed in 218 Korean women who had received the uniformly planned chemotherapy. With regard to ABCB1 3435 C>T, ABCB1 3435 T/T had significantly higher risks of neutropenia (P = 0.015). Meanwhile, allele frequencies for CYP3A5 6986 G and ABCB1 3435 T revealed a trend for neutropenia (P = 0.107 and 0.068). We could not find any other association between genotypes and other toxicities., Discussion: Although ABCB1 3435 T/T was significantly associated with docetaxel-related neutropenia in our study population, polymorphism of pharmacogenetic genes related to docetaxel metabolism did not appear to be evidently associated with docetaxel-related adverse events.

Purpose: This phase II study evaluated the feasibility and efficacy of one cycle of induction chemotherapy, followed by concurrent chemoradiotherapy (CRT) featuring capecitabine/cisplatin, followed in turn by surgery, in the treatment of patients with resectable esophageal squamous cell carcinoma., Methods: Between March 2003 and April 2005, 54 patients with stage II or III esophageal cancer were treated with induction chemotherapy (cisplatin 60 mg/m(2) on day 1; capecitabine 1,000 mg/m(2) bid on days 1-14) followed by concurrent radiotherapy (46 Gy in 23 fractions) and chemotherapy (cisplatin 30 mg/m(2) on days 1, 8, 15, and 22; capecitabine 800 mg/m(2) bid 5 days/week). Surgery was performed within 8 weeks of the end of radiotherapy., Results: Median age of the patients was 64.5 years (range, 45-74 years). After CRT, 52 patients (96%) showed a clinical response, including 26 (48%) who exhibited a complete response (CR). Surgery was performed on 41 patients (76%), with 20 (37%) achieving pathologic CR and 3 (6%) dying of postoperative pneumonia. At a median follow-up time of 74.2 months (range, 64.3-84.8 months), 16 patients (30%) had experienced tumor recurrence and 36 (67%) had died. Of the 41 patients who underwent esophagectomy, 5 (12%) had exclusively locoregional disease and 7 (17%) had distant metastasis, whereas no one had both. The 5-year progression-free and overall survival rates were 30.2% (95% confidence interval [CI], 18.0-42.4%) and 37.0% (95% CI, 24.1-50.0%), respectively., Conclusions: A trimodal approach, consisting of a single cycle of induction chemotherapy, CRT containing capecitabine and cisplatin, and surgery, was feasible and effective in patients with resectable esophageal squamous cell carcinoma.

Ethnic and regional differences in the epidemiology and pathological aspects of Hodgkin's lymphoma (HL) between Western and Asian patients may be associated with differences in clinical features and prognosis. We retrospectively analyzed the clinical and histopathological characteristics, therapeutic outcomes, and prognostic factors of 539 HL patients treated at 16 centers in Korea. We found that the incidence of histological subtypes of HL in Korea was similar to that in Western and other Asian countries. However, the incidence peaked between 16 and 30 years of age, unlike the bimodal age distribution seen in Western countries. In patients with stage I-IIA non-bulky disease, the complete response (CR) rate was similar between combined modality therapy and chemotherapy alone (93% vs. 84%, P = 0.44), and there was no difference in relapse-free survival (RFS) and overall survival (OS). Patients with stage I-II disease plus unfavorable factors and those with advanced-stage disease treated with combination chemotherapy regimens had an overall CR rate of 77%, with no difference between doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and non-ABVD regimens (77.2% vs. 76.8%, P = 0.95). Among those patients who achieved final CR, there was no significant difference in RFS or OS between those who achieved interim CR and PR. Only the presence of B symptoms was independently predictive of a shorter RFS. Age > 45 years, Eastern Cooperative Oncology Group 2-4, and B symptoms were independent risk factors for death. Although the incidence of HL was lower in Korea than in Western countries, the distribution of morphological subtypes, treatment outcomes, and patient prognosis were similar.

Positron emission tomography (PET) has been found useful in monitoring response to treatment of malignant lymphoma. We investigated the ability of interim PET to monitor response to standard dose R-CHOP chemotherapy in chemotherapy-naïve patients with diffuse large B-cell lymphoma (DLBCL). Between March 2004 and April 2009, 155 DLBCL patients treated with R-CHOP and available for interim and post-treatment PET/CT were identified and included in this analysis. Response, progression-free survival (PFS), and overall survival (OS) were compared between interim PET/CT-negative and positive group, and among three patient groups which were categorized based on their interim and post-treatment PET/CT: those with early metabolic complete response (mCR), delayed mCR, and never mCR. Interim PET/CT-negative patients (n=100) showed superior CR rates to interim PET/CT-positive patients (n=55; 93% vs 62%, P<0.001). However, there was no difference in PFS (P=0.07) and OS (P=0.24) between interim PET/CT-negative and positive group. We categorized patients into three groups, with 100 (64%) in the early mCR group, 35 (23%) in the delayed mCR group, and 20 (13%) in the never mCR group. Early mCR and delayed mCR group did not differ significantly in PFS (P=0.84) or OS (P=0.20). However, the survival outcome in the never mCR group was significantly inferior to the combined early and delayed mCR group. The result from this study suggests that interim PET/CT might be an inappropriate tool for designing risk-adaptive therapy in chemotherapy-naïve DLBCL patients treated with R-CHOP. Prospective trials should be performed to clearly determine the role of interim PET/CT.