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Waldenström's macroglobulinemia (WM) is a B-cell proliferative malignancy characterized by immunoglobulin M monoclonal gammopathy and bone marrow infiltration by lymphoplasmacytic cells. Clinical features and cytogenetics of WM in Asia including Republic of Korea remain unclear. Moreover, no study has reported treatment outcomes in patients with WM treated with novel agent combined with conventional chemotherapy. This study investigated clinical features and assessed treatment outcomes with novel agent and conventional chemotherapy in Republic of Korea. Data from all (n = 71) patients with newly diagnosed WM at 17 hospitals who received chemotherapy between January 2005 and December 2012 were collected retrospectively. The median age of patients was 66 years (range: 37-92 years) and male to female ratio was 5 : 1. Patients treated with novel agent combined chemotherapy displayed higher overall response rate (ORR) compared to conventional chemotherapy alone (92.9% versus 52.6%, P = 0.006). The 5-year overall survival rate was 62.6% (95% confidence interval: 34.73-111.07). Use of novel agents produced higher ORR but survival benefit was not apparent due to the small number of patients and short follow-up duration. Further studies are needed to confirm the efficacy of novel agents in patients with WM.

Purpose: This multicenter, open-label, phase II trial evaluated the efficacy and safety of bortezomib combined with dexamethasone for the treatment of relapsed/refractory cutaneous T-cell lymphoma (CTCL) in previously treated patients across 14 institutions in South Korea. Materials and Methods: Between September 2017 and July 2020, 29 patients with histologically confirmed CTCL received treatment, consisting of eight 4-week cycles of induction therapy followed by maintenance therapy, contingent upon response, for up to one year. The primary endpoint was the proportion of patients achieving an objective global response. Results: Thirteen of the 29 patients (44.8%) achieved an objective global response, including two complete responses. The median progression-free survival (PFS) was 5.8 months, with responders showing a median PFS of 14.0 months. Treatment-emergent adverse events were generally mild, with a low incidence of peripheral neuropathy and hematologic toxicities. Despite the trend toward shorter PFS in patients with higher mutation burdens, genomic profiling before and after treatment showed no significant emergence of new mutations indicative of disease progression. Conclusion: This study supports the use of bortezomib and dexamethasone as a viable and safe treatment option for previously treated CTCL, demonstrating substantial efficacy and manageability in adverse effects. Further research with a larger cohort is suggested to validate these findings and explore the prognostic value of mutation profiles. [ABSTRACT FROM AUTHOR]

4 ‡ Parotid gland (from stage IE to IVE), stomach (from stage IE to IVE, confirmed on EGD), thigh muscle (from stage IE to IVE), iliac/inguinal lymph nodes (stage IIE to IVE). 5 § The bone marrow involvement of mucosa-associated lymphoid tissue (MALT) lymphoma was not detectable by PET or CT scans. Keywords: ocular adnexal lymphoma; extranodal marginal zone lymphoma; MALToma; positron emission tomography; bone marrow biopsy; esophagogastroduodenoscopy EN ocular adnexal lymphoma extranodal marginal zone lymphoma MALToma positron emission tomography bone marrow biopsy esophagogastroduodenoscopy 848 851 4 05/17/21 20210515 NES 210515 Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) accounts for 30-90% of ocular adnexal lymphoma, and a majority of ocular adnexal MALT lymphoma (OAML) is stage 1 disease.1 The role of extensive staging procedures, including positron emission tomography-computed tomography (PET-CT), esophagogastroduodenoscopy (EGD), and bone marrow biopsy, has not been thoroughly investigated for OAML due to its rarity. Half of stage IIE patients ( I n i = 4/8) and two-thirds of stage IV patients ( I n i = 6/9) received rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP). [Extracted from the article]

Summary: The mucosa‐associated lymphoid tissue (MALT) International Prognostic Index (IPI) was recently proposed as a prognostic index for patients with MALT lymphoma. We aimed to investigate the prognostic value of the serum β2‐microglobulin level in the context of MALT‐IPI, and we proposed a new prognostic index. Survival outcomes were analysed with regard to β2‐microglobulin level, MALT‐IPI, and the new prognostic index in MALT lymphoma patients (n = 571). The validity of the new prognostic index was assessed using an independent cohort (n = 216). Patients with high β2‐microglobulin levels had significantly worse progression‐free survival (PFS) and overall survival (OS) outcomes. A high β2‐microglobulin level was independently associated with poor PFS and OS. β2‐microglobulin levels further stratified patients in the MALT‐IPI intermediate‐risk group in terms of PFS and OS. A new prognostic index based on the MALT‐IPI and the β2‐microglobulin level, MALT‐IPI‐B, was proposed. The MALT‐IPI‐B was able to stratify patients into subgroups having distinct PFS and OS outcomes in both the training and validation cohorts. MALT‐IPI‐B enabled the identification of patients with poor survival outcomes who were classified into the intermediate‐risk group by the MALT‐IPI. In conclusion, this new β2‐microglobulin‐based prognostic index may have the specific advantage of identifying high‐risk patients who may require systemic treatment. [ABSTRACT FROM AUTHOR]

BCL2 translocation is the genetic hallmark of follicular lymphoma (FL). Besides BCL2 translocation, copy number (CN) gains and translocations of BCL6, MYC, and IRF4 have also been detected in FL, but there is little information regarding their prognostic significance. This retrospective study used fluorescence in situ hybridization (FISH) to analyze BCL2, BCL6, MYC, and IRF4 translocations and CN gains in 105 FL cases. Genetic translocations were detected for BCL2 (n = 64; 72.7%), BCL6 (n = 14; 15.9%), and MYC (n = 2; 2.3%); no case showed IRF4 translocation. Overall, 23 (26.1%), 30 (34.1%), 12 (13.8%), and 10 (11.0%) cases showed CN gains in BCL2, BCL6, MYC, and IRF4, respectively. BCL6 CN gain was a prognostic factor for worse overall survival, demonstrating a trend toward significance in multivariate analysis (HR =8.769, p = 0.056). BCL6 CN gain in FL might be associated with aggressive biologic behavior. [ABSTRACT FROM AUTHOR]

Background: Extranodal natural killer T cell lymphoma (ENKTL) is a rare subtype of non-Hodgkin lymphoma with invariable infection of lymphoma cells with Epstein-Barr virus (EBV), and the presence of EBV-DNA in the blood is a well-known prognosticator. However, there is no consensus on which blood compartment is more optimal for predicting survival outcomes. Methods: We analyzed 60 patients who were newly diagnosed with ENKTL from a prospectively collected database. EBV-DNA was measured in the whole-blood (WB) and plasma at the time of diagnosis and after treatment completion. Results: EBV-DNA was detected in pre-treatment WB and plasma in 37 (61.7%) and 23 (38.3%) patients, respectively. The presence of pre-treatment plasma EBV-DNA was significantly associated with advanced stage while presence of WB EBV-DNA did not. Positivity of pre-treatment plasma-EBV, but not WB EBV-DNA, was independently associated with poor PFS (HR, 4.22;95% CI, 1.79–9.97; P =0.001) and OS (HR, 8.38; 95% CI, 3.03–23.19; P <0.001) in the multivariate analysis. After treatment completion, positivity of plasma-EBV was independently associated with poor PFS (HR, 9.41; 95% CI, 2.27–39.02; P =0.002) and OS (HR, 32.38; 95% CI, 3.25–322.56; P =0.003), whereas no significant association was observed between WB-EBV status and survival outcomes. Conclusions: Our results suggest that EBV-DNA in the plasma has better prognostic values than WB in patients with ENKTL. [ABSTRACT FROM AUTHOR]

The risk stratification of diffuse large B-cell lymphoma (DLBCL) is crucial. The International Prognostic Index, the most commonly used and the traditional risk stratification system, is composed of fixed and artificially dichotomized attributes. We aimed to develop a novel prognostic model that allows the incorporation of up-to-date attributes comprehensively without information loss. We analyzed 204 patients with primary DLBCL who were uniformly treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) from 2007 to 2012 at Asan Medical Center. Using the multivariable fractional polynomial (MFP) method and bootstrap resampling, we selected the variables of significance and the best fitted functional form in fractional polynomials. Age, serum β2-microglobulin, serum lactate dehydrogenase, and BCL2 expression were selected as significant variables in predicting overall survival (OS), while age was excluded in predicting 2-years event-free survival. The prognostic score calculated by the MFP model effectively classifies patients into four risk groups with 5-years OS of 89.91% (low risk), 81.21% (low-intermediate risk), 66.40% (high-intermediate risk), and 37.89% (high risk). We suggest a new prognostic model that is simple and flexible. By using the MFP method, we can incorporate various clinicopathologic factors into a risk stratification system without arbitrary dichotomization. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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/m2 on days 1 to 4, i.v. methylprednisolone 500 mg on days 1 to 5, i.v. cytarabine 2 g/m2 on day 5, and i.v. oxaliplatin 130 mg/m2 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. [ABSTRACT FROM AUTHOR]

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-II1&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 (IIE-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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV) is a significant contributor to the development of classical Hodgkin's lymphoma (cHL). Recent studies have documented associations between angiogenesis and EBV-associated malignancies. No study has yet examined the associations among, and prognostic implications of, EBV infection, vascular endothelial growth factor (VEGF) expression, and microvessel density (MVD) in cHL patients. Diagnostic tissues from 135 cHL patients treated with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) were retrospectively evaluated by in situ hybridization of EBV-encoded small RNA (EBER) and immunohistochemical staining for VEGF and CD31 (a measure of MVD). EBER and VEGF expression were positively correlated (P = 0.038). The mean MVD value of EBER-positive tumors was significantly higher than that of EBER-negative tumors (P = 0.034). The mean MVD of tumors positive for both EBER and VEGF was significantly higher than that of tumors negative for both markers (P = 0.008). EBER-positive patients had a lower 5-year overall survival (OS) rate than EBER-negative patients (P = 0.046). A high MVD was also associated with a poorer OS (P = 0.01); multivariate analysis showed that this was a significant and independent prognostic factor (P = 0.026). We found positive correlations between EBER and VEGF levels, and the MVD, indicating that EBV plays an important role in tumor angiogenesis. Targeting of both angiogenesis and EBV may be important when treating cHL patients who are EBER-positive and/or have a high MVD. [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]

Background: The clinical outcome of extranodal natural killer T-cell lymphoma (ENKTL) has improved substantially as a result of new treatment strategies with non-anthracycline-based chemotherapies and upfront use of concurrent chemoradiotherapy or radiotherapy. A new prognostic model based on the outcomes obtained with these contemporary treatments was warranted.Methods: We did a retrospective study of patients with newly diagnosed ENKTL without any previous treatment history for the disease who were given non-anthracycline-based chemotherapies with or without upfront concurrent chemoradiotherapy or radiotherapy with curative intent. A prognostic model to predict overall survival and progression-free survival on the basis of pretreatment clinical and laboratory characteristics was developed by filling a multivariable model on the basis of the dataset with complete data for the selected risk factors for an unbiased prediction model. The final model was applied to the patients who had complete data for the selected risk factors. We did a validation analysis of the prognostic model in an independent cohort.Findings: We did multivariate analyses of 527 patients who were included from 38 hospitals in 11 countries in the training cohort. Analyses showed that age greater than 60 years, stage III or IV disease, distant lymph-node involvement, and non-nasal type disease were significantly associated with overall survival and progression-free survival. We used these data as the basis for the prognostic index of natural killer lymphoma (PINK), in which patients are stratified into low-risk (no risk factors), intermediate-risk (one risk factor), or high-risk (two or more risk factors) groups, which were associated with 3-year overall survival of 81% (95% CI 75-86), 62% (55-70), and 25% (20-34), respectively. In the 328 patients with data for Epstein-Barr virus DNA, a detectable viral DNA titre was an independent prognostic factor for overall survival. When these data were added to PINK as the basis for another prognostic index (PINK-E)-which had similar low-risk (zero or one risk factor), intermediate-risk (two risk factors), and high-risk (three or more risk factors) categories-significant associations with overall survival were noted (81% [95% CI 75-87%], 55% (44-66), and 28% (18-40%), respectively). These results were validated and confirmed in an independent cohort, although the PINK-E model was only significantly associated with the high-risk group compared with the low-risk group.Interpretation: PINK and PINK-E are new prognostic models that can be used to develop risk-adapted treatment approaches for patients with ENKTL being treated in the contemporary era of non-anthracycline-based therapy.Funding: Samsung Biomedical Research Institute. [ABSTRACT FROM AUTHOR]

Although serum beta-2 microglobulin (B2M) has been suggested as a prognostic factor for mantle cell lymphoma (MCL), additional data are necessary to confirm its role. Between November 2005 and July 2014, a total of 52 patients with MCL were identified from the database of Asan Medical Center, Seoul, Korea. Pretreatment serum B2M information was available in 50 patients (96%). Overall survival (OS) was compared according to the serum B2M level with a cut-off value of 2.5 mg/L. The median MCL international prognostic index (MIPI) score was 5.84 (range 4.72-7.80), and the median biologic MIPI (MIPI-b) score was 6.27 (4.93-8.47). Pretreatment serum B2M was elevated in 30 patients (60%) and was significantly related to advanced stage (p = 0.02) and high MIPI (p = 0.03) and MIPI-b (p = 0.03) scores. With median follow-up duration of 29.8 months (range 0.8-87.0 months), the median OS was 56.2 months [95% confidence interval (CI) 36.6-75.9 months] in all patients, and serum B2M was significantly associated with OS (p = 0.001). In multivariate analyses adjusted for MIPI or MIPI-b scores and rituximab, elevated serum B2M was significantly associated with poor OS (when adjusting MIPI, hazard ratio = 26.4, 95% CI 2.9-241.3, p = 0.004; when adjusting MIPI-b, hazard ratio = 20.1, 95% CI 2.4-170.1, p = 0.006). Thus, pretreatment serum B2M may be an independent and significant prognostic factor in patients with MCL. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: Mantle cell lymphoma (MCL) has a heterogeneous clinical course. Although most cases show a poor prognosis, a minority has an indolent course. It is difficult to identify indolent MCL cases prospectively. T-cell leukemia/lymphoma protein 1 (TCL1) is expressed by several B-cell lymphomas, including MCL. This study examined the expression of TCL1 and its prognostic relevance for MCL. Methods: Clinical data for 162 patients with MCL were collected. Of these, 144 cases with available tissues for tissue microarray construction and immunostaining were included in the analysis. TCL1 staining was quantified using the Nuclear Quant application with Pannoramic™ Viewer v. 1.14. High TCL1 expression was defined as moderate to strong nuclear and/or cytoplasmic staining in 40% or more of the cells. Results: High TCL1 expression was observed in 39 of 144 samples (27.1%). Patients with low TCL1 expression were more likely to present with blastoid/pleomorphic morphology (P = 0.010). Low TCL1 expression was associated with significantly shorter overall survival (OS, P = 0.006). Multivariate analysis identified low TCL1 expression (P = 0.003), high-risk MIPI (P = 0.027), and anemia (P = 0.018) as adverse prognostic factors. Conclusions: Our study suggests that TCL1 expression profile may have a role in the prediction of overall outcome in patient with MCL and call for prospective studies. [ABSTRACT FROM AUTHOR]

Even though local stage (Ann Arbor stage I/II) marginal zone lymphoma (MZL) is well controlled with local treatment-based therapy, no data exist on the role of additional chemotherapy after local treatment for stage I/II MZL. Patients with biopsy-confirmed Ann Arbor stage I/II MZL (n = 210) were included for analysis in this study. Of these, 180 patients (85.7 %) were stage I and 30 (14.3 %) were stage II. Most patients (n = 182, 86.7 %) were treated with a local modality including radiation therapy or surgery and 28 (13.3 %) received additional systemic chemotherapy after local treatment. The overall response rate was 98.3 % (95 % CI 96-100 %), with 187 complete responses and 20 partial responses. In the local treatment group, the mean progression-free survival (PFS) was 147.4 months (95 % CI 126.7-168.1 months) and the overall survival (OS) was 188.2 months (95 % CI 178.8-197.7 months). In the additional chemotherapy group, the mean PFS was 103.4 months (95 % CI 84.9-121.9 months) and the OS was 137.3 months (95 % CI 127.9-146.7 months). There was no difference between the two groups in OS (p = 0.836) and PFS (p = 0.695). Local stage MZL has a good clinical course and is well controlled with a local treatment modality without additional chemotherapy. [ABSTRACT FROM AUTHOR]

Recent studies suggest that absolute lymphocyte count, absolute monocyte count and their ratio [lymphocyte/monocyte ratio (LMR)] at diagnosis may predict survival in classical Hodgkin lymphoma (cHL). Here, we investigated the prognostic significance of LMR in cHL patients in relation to age of patients. Subjects included 351 cHL patients (age range from 4 to 84 years, median age 34 years, sex ratio 1.58) who had been followed-up for a median period of 59 months (range, 0.1-245 months). The estimated 5-year overall survival (OS) rate was 86.8%. Subgroup analysis was performed according to patients' age; non-elderly group (<60 years of age) versus elderly group (≥60 years of age). There was no significant difference in the level of absolute lymphocyte count, absolute monocyte count or LMR between the age groups. Using receiver operating characteristic curve analysis, the optimal cut-off value of LMR for the entire cohort was determined at 2.8, whereas the optimal cut-off for the elderly group was 2.2. In the non-elderly group (<60 years old), patients with LMR <2.8 had significantly lower OS or lymphoma-specific survival compared with those with LMR ≥2.8 (p < 0.001, both). In contrast, neither the LMR value of 2.8 or 2.2 predicted survival in the elderly group. In multivariate analysis, LMR remained a significant prognostic factor for OS (p = 0.049). The results of our analysis suggest that low LMR is associated with poor OS in patients of <60 years old. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine the prognostic significance of insulin-like growth factor-1 receptor ( IGF-1R) expression alone and in relation to the expression of the MET- receptor and the MET-homologous receptor RON, in classical Hodgkin's lymphoma ( cHL). Tumour samples from patients with cHL ( n = 202; median age 37.5 years) were analysed retrospectively for IGF-R1, MET or RON expression by immunohistochemistry using tissue microarrays. The median follow-up time was 3.7 years (range, 0.1-20 years). Twenty-nine patients (14.3%) expressed IGF-1R protein in Hodgkin/Reed-Sternberg ( HRS) cells, which was associated with a better overall survival ( OS) ( P = 0.036). IGF-1R expression was closely associated with MET receptor expression and low level of lactate dehydrogenase. In patients with cHL receiving doxorubicin, bleomycin, vinblastine and dacarbazine, those expressing IGF-1R showed a trend towards better OS and event-free survival than IGF-1R-negative patients ( P = 0.129 and P = 0.115 respectively), but statistical significance was not reached. This study suggests that IGF-1R expression could be associated with better clinical outcome in cHL but is significantly associated with the expression of MET receptor. [ABSTRACT FROM AUTHOR]

Although serum β2-microglobulin (B2M) has been suggested as a prognostic factor for several hematologic malignancies, it has not been comprehensively investigated in non-gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Between January 2000 and May 2013, a total of 174 patients with non-gastric MALT lymphoma were identified from a prospectively developed database. Baseline serum B2M was elevated in 17 (10%) patients. In univariate analysis, serum B2M ≥ 2.5 mg/L was significantly associated with progression-free survival (PFS, p < 0.001) and overall survival (OS, p < 0.001). Multivariate analysis identified serum B2M as an independent prognostic factor in PFS (hazard ratio [HR] = 3.5, 95% confidence interval [CI]: 1.2-10.0; p = 0.02) and OS (HR = 26.9, 95% CI: 2.7-269.7; p = 0.005), after adjustment for IPI and treatment modalities. Baseline serum B2M is an independent prognostic factor in patients with non-gastric MALT lymphoma. [ABSTRACT FROM AUTHOR]

Mantle cell lymphoma (MCL) is characterized by a variable clinical course in which patients can experience indolent disease or frequent relapses despite a good initial response to conventional therapy. Risk stratification of MCL is most frequently performed using the MCL International Prognostic Index (MIPI). Recent studies indicate that the peripheral blood absolute monocyte count (AMC) and tumour-associated macrophages may reflect the state of the tumour microenvironment in lymphomas. The significance of AMC and tumour-associated macrophages in the clinical course of MCL is unknown. The prognostic impact of the AMC, of CD68 expression and of CD163 expression was retrospectively examined in 103 MCL samples using the receiver operating characteristic curved. Patients with an AMC ≥ 375 cells/μL at diagnosis were more likely to present with advanced-stage disease ( p = 0.026), leukocytosis ( p < 0.001), lymphocytosis ( p = 0.01) and granulocytosis ( p = 0.003). On univariate analysis, a high AMC (≥375 cells/μL) correlated with poorer overall survival (OS) ( p = 0.01). Neither CD68 nor CD163 expression was significantly associated with either OS or event-free survival. Multivariate analysis showed that a high AMC was a prognostic factor for OS, independent of the MIPI [hazards ratio (HR), 1.811; 95% confidence interval, 1.018-3.223; p = 0.043]. This study demonstrates that the AMC at the time of diagnosis is an independent prognostic factor for OS in MCL, which suggests the possibility that AMC may be used in addition to the MIPI to predict outcome in patients with MCL. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objectives A recent study suggested a prognostic role for the peripheral blood absolute lymphocyte/monocyte ratio ( LMR) at diagnosis of diffuse large B-cell lymphoma ( DLBCL). Here, we investigated the significance of LMR in DLBCL patients in relation to advanced age. Methods We examined the prognostic impact of LMR in 603 DLBCL treated with rituximab plus CHOP, using the receiver operating characteristic curve analysis for optimal cut-off values, and performed a subgroup analysis according to age. Results In elderly groups (age ≥ 70), absolute monocyte count was significantly increased, whereas LMR was significantly decreased compared to younger groups. Patients under 70 yr of age with LMR <3.04 had significantly lower overall survival ( OS) and progression-free survival ( PFS) compared to those with LMR ≥3.04 ( P < 0.001 for both). However, in elderly patients (age ≥ 70), there was no significant difference in OS between patients' LMR levels using the 3.04 cut-off value ( P = 0.059). Therefore, a new LMR cut-off value of 2.36 was selected in elderly patients, having observed that elderly patients with LMR <2.36 had significantly lower OS compared to those with LMR ≥2.36 ( P = 0.021). In multivariate analysis, LMR remained a significant prognostic factor for OS ( P = 0.004) or PFS ( P < 0.001). Conclusions We suggest the use of a different cut-off value of LMR in elderly patients to distinguish high-risk from low-risk groups. [ABSTRACT FROM AUTHOR]

Background: Recent studies have reported the prognostic value of tissue-associated magrophages (TAMs) in classical Hodgkin lymphoma (cHL). In addition, TAMs are implicated in the tumor angiogenesis. In this study, we examined the prognostic relevance of TAMs in relation to vascular endothelial growth factor (VEGF) expression and angiogenesis in uniformly treated cases of cHL. Methods: Diagnostic tissue from 116 patients with ABVD-treated cHL was evaluated retrospectively by immunohistochemical analysis for CD68, CD163 and VEGF expression and for CD31 expression as a measure of microvessel density (MVD). Results: High CD163 expression (≥35% of cellularity) correlated with VEGF expression (Pearson’s Chi-square test, P = 0.008) and MVD (Spearman correlation coefficient 0.310, P<0.001). High CD163 expression was associated with inferior event-free survival (EFS, P = 0.005) and overall survival (OS, P<0.001) in univariate analysis. In multivariate analysis, high CD163 expression was strongly associated with inferior EFS (P = 0.043) and OS (P = 0.008). Patients with high MVD had a lower OS than those with low MVD, but the difference was not significant (P = 0.071, respectively). While high expression of CD68 was also associated with inferior EFS (P = 0.007), it showed no correlation with VEGF or MVD. Conclusions: Our data confirms that CD163 expression provides independent prognostic information in cHL. The correlation of CD163 with VEGF expression and MVD suggests the role of CD163-positive cells in tumor angiogenesis of cHL. [ABSTRACT FROM AUTHOR]

Conclusions: p16 immunohistochemistry (IHC) status correlated with less exposure to smoking and/or alcohol in Korean patients with locally advanced tonsillar squamous cell carcinoma (TSCC), and was an independent prognostic factor for survival. Objective: TSCC is more likely to be human papillomavirus (HPV)-positive than other head and neck squamous cell carcinoma (HNSCC) subtypes. The objective of this study was to ascertain the HPV status of TSCC in Korean patients and to determine its relationship with clinical parameters and prognosis. Methods: The locally advanced TSCCs of 79 patients who were treated between 2000 and 2008 were tested by p16 IHC and HPV in situ hybridization (ISH) with a tissue microarray. Results: Sixty-three patients (80%) were positive for p16 IHC, while 54 (68%) were positive by HPV ISH. p16 IHC status correlated significantly with lower exposure to smoking and alcohol ( p < 0.05) but did not correlate with T and N stage classification, histological differentiation, age, or gender. The p16-positive group had a significantly higher 5-year overall survival rate in comparison with the p16-negative group (78% vs 63%, hazard ratio (HR) = 0.347, 95% CI = 0.14, 95% C p = 0.025). p16 IHC was a favorable independent prognostic factor for overall survival, even after adjustment for age and T stage (HR = 0.283, 95% CI = 0.103, 95% p = 0.015). [ABSTRACT FROM AUTHOR]

Objective The clinical features of extranodal natural killer ( NK)/ T-cell lymphoma ( ENKL) that originates in extranasal sites are less well defined than those of ENKL that originates in nasal sites. Therefore, we compared the clinical characteristics and prognoses of patients with nasal ENKL and patients with extranasal ENKL. Methods We retrospectively analyzed 117 consecutive patients with ENKL that included 89 (76.1%) with nasal and 28 (23.9%) with extranasal disease. Results Extranasal ENKL was associated with more adverse clinical features than nasal ENKL, which included the presence of B symptoms, stage III/ IV disease, ≥2 extranodal sites, and involvement of regional lymph nodes and bone marrow. After a median follow-up of 33.1 months (range, 0.7-152.2 months), the median overall survival ( OS) of patients with extranasal and nasal NK/ T-cell lymphoma was 8.6 and 86.5 months, respectively. Multivariate analysis revealed that extranasal NK/ T-cell lymphoma was a significant factor that affects OS. When patients with extranasal ENKL were classified into low-risk and high-risk categories according to the Korean Prognostic Index ( KPI) and International Prognostic Index ( IPI), these indices categorized the two groups with significantly different survival outcomes ( P = 0.025 and 0.035, respectively). Conclusions Patients with extranasal ENKL have worse clinical outcomes than those with nasal ENKL. The KPI and IPI appear useful for the prognosis of patients with extranasal ENKL. [ABSTRACT FROM AUTHOR]

Background: Limited progress had been made in prognostic stratification of patients with Hodgkin lymphoma (HL) until recent studies suggested that the number of CD68-expressing macrophages is prognostic in classical HL. However, its significance in Asian patients with HL has not been explored yet perhaps because of its low incidence in Asia. Methods: In this work, we performed immunohistochemical analysis of CD163, as well as CD68, in 144 Korean patients with HL treated between November 1990 and December 2009 in a single center. The relative percentages of CD68+ and CD163+ cells with respect to the overall cellularity (CD68 index and CD163 index, respectively) were correlated with clinical outcomes. Results: Both high CD68 and CD163 indices (>20%) were associated with a rise in treatment-related deaths and poorer event-free survival ( P = 0.009 and P = 0.0023, respectively), disease-specific survival ( P = 0.011 and P = 0.001), and overall survival ( P = 0.023 and P = 0.001). In particular, a high CD163 index was related to lower complete response (CR) rate ( P = 0.022) and shorter duration of CR ( P = 0.030). Conclusions: High index of either CD68 or CD163 (>20%) is significantly correlated with poor prognosis in Korean patients with HL. CD163, a specific marker of macrophages, seems to be another prognostic factor for classical HL. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Limited data exist on up-front autologous stem cell transplantation (ASCT) in extranodal natural killer/T cell lymphoma (ENKTL). Sixty-two patients (43 men and 19 women) with newly diagnosed ENKTL who underwent up-front ASCT after primary therapy were identified. Poor-risk characteristics included advanced stage (50%), high-intermediate to high-risk International Prognostic Index (25.8%), and group 3 to 4 of NK/T Cell Lymphoma Prognostic Index (NKPI, 67.7%). Pretransplant responses included complete remission in 61.3% and partial remission in 38.7% of patients, and final post-transplantation response included complete remission in 78.3%. Early progression occurred in 12.9%. At a median follow-up of 43.3 months (range, 3.7 to 114.6), 3-year progression-free survival (PFS) was 52.4% and 3-year overall survival (OS) was 60.0%. Patients with limited disease had significantly better 3-year PFS (64.5% versus 40.1%, P = .017) and OS (67.6% versus 52.3%, P = .048) than those with advanced disease. Multivariate analysis showed NKPI and pretransplant response were independent prognostic factors influencing survival, particularly NKPI in limited disease and pretransplant response in advanced disease. Radiotherapy was an independent factor for reduced progression and survival in patients with limited disease, but anthracycline-based chemotherapy was a poor prognostic factor for progression in patients with advanced disease. Up-front ASCT is an active treatment in ENKTL patients responding to primary therapy. [ABSTRACT FROM AUTHOR]