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Although the role of high dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT) in the treatment of aggressive lymphoma has been established in several large prospective studies, its effectiveness in patients with peripheral T cell lymphoma (PTCL) has not been defined. We aimed to evaluate the efficacy of HDT and ASCT and prognostic factors for survival in patients with PTCL. We retrospectively analyzed the results of 40 PTCL patients treated with HDT and ASCT at Asan Medical Center between January 1995 and December 2005. Twenty patients had PTCL-U (peripheral T cell lymphoma, unspecified), 10 had extranodal natural killer/T cell lymphoma, 5 had anaplastic large cell lymphoma, 3 had angioimmunoblastic T cell lymphoma, 1 had hepatosplenic γσ T cell lymphoma, and 1 had disseminated mycosis fungoides. Disease status at transplant was complete response (CR)1 in 3 patients, CR2 or greater in 8, partial remission in 25, and refractory in 4. At a median follow-up of 16 months (range, 5 to 135 months) for surviving patients, the median overall survival (OS) was 11.5 months and the 1-year probability of survival was 46.1%. The median event free survival (EFS) was 3.6 months (95% confidence interval, 2.5 to 4.8 months). Ten patients (25%) remain alive without evidence of disease. The median OS of 11 patients with CR at ASCT was not reached; of these, 7 patients (63.6%) were alive with CR. In multivariate analysis, CR at ASCT was a prognostic factor for EFS ( P = 0.025) and OS ( P = 0.027) and normal lactate dehydrogenase (LDH) at ASCT was a prognostic factor for improved OS ( P = 0.025). Chemosensitive patients with PTCL who achieved CR before ASCT seem to benefit from HDT and ASCT. Pretransplant values of LDH had potential to predict the survival. [ABSTRACT FROM AUTHOR]

Endothelial progenitor cells (EPCs) participate in neovascularization and are consistent with postnatal vasculogenesis. In vitro, they differentiate into endothelial cells (ECs). Prior reports have suggested that circulating human AC133+ cells have the capacity to differentiate into ECs as progenitor cells. However, recent studies have demonstrated that circulating CD34−CD14+ cells also have EPC-like properties in vitro and in vivo. We tested whether AC133−CD14+ cells from human umbilical cord blood (HUCB) have the potential to differentiate into ECs. The AC133−CD14+ cells were isolated from HUCB by magnetic bead selection and cultured on fibronectin-coated six-well trays in M199 medium supplemented with fetal bovine serum (FBS), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and insulin growth factor (IGF-1). The AC133−CD14+ cells adhered slightly within 1 day of culture and subsequently underwent a distinct process of morphological transformation to spindle-shaped cells that sprouted from the edge of the cell clusters. After 14 days, the cells formed cord- and tubular-like structures. The AC133−CD14+ cells showed a strong increase in the endothelial marker P1H12 over time, whereas CD14 decreased, and CD45 did not change, respectively. In addition, the cells expressed endothelial markers von Willebrand’s factor (vWF), platelet/endothelial cell adhesion molecule-1 (PECAM-1), vascular endothelial growth factor receptor-1 (VEGFR-1)/Flt-1, VEGFR-2/Flk-1, eNOS, and VE-cadherin, but did not express Tie-2 after 7 days of culture. The present data indicate that AC133−CD14+ cells from HUCB are able to develop endothelial phenotype with expression of endothelial-specific surface markers and even form cord- and tubular-like structures in vitro as progenitor cells. [ABSTRACT FROM AUTHOR]

18F-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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 β-microglobulin, albumin, creatinine, and ASCT were also independent prognostic factors for OS. Further investigation is required to establish the mechanisms underlying APB in MM. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Although a few studies have evaluated the utility of F-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. [ABSTRACT FROM AUTHOR]

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 β-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 β-microglobulin in primary gastric DLBCL might be able to discriminate the patients' prognosis who are treated with R-CHOP chemotherapy. [ABSTRACT FROM AUTHOR]