BackgroundA phase II trial of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (DA-EPOCH-R) from the National Cancer Institute showed promising activity in untreated diffuse large B-cell lymphoma. The Cancer and Leukemia Group B conducted a study to determine if these results could be reproduced in a multi-institutional setting. Design and MethodsThe study included 69 patients with untreated diffuse large B-cell lymphoma at least 18 years of age and at least stage II. Radiaton therapy was not permitted on study. Median age was 58 years (range 23-83) and 40% had high-intermediate or high International Prognostic Index risk. Immunohistochemical biomarkers for cell of origin and proliferation were performed. ResultsWith a median follow up of 62 months, time to progression and overall survival were 81% and 84%, respectively, and time to progression was 87%, 92% and 54% for low/low-intermediate, high-intermediate and high International Prognostic Index risk groups, respectively, at 5-years and beyond. The time to progression and event-free survival of germinal center B-cell lymphoma were 100% and 94%, respectively, and non-germinal center B-cell GCB diffuse large Bcell lymphoma were 67% and 58%, respectively, at 62 months (germinal center vs. non-germinal center B cell P=0.008). DA-EPOCH-R was tolerated without significant grade 4 non-hematologic toxicities. ConclusionsThese results provide the first confirmation by a multi-institutional group that DA-EPOCH-R provides high durable remissions in diffuse large B-cell lymphoma and is effective in both germinal center and non-germinal center B-cell subtypes. The trial was registered at ClinicalTrials.Gov (NCT00032019).Key words: diffuse large B-cell lymphoma, DA-EPOCH-rituximab, untreated, outome, molecular. subtype. Haematologica 2012;97(5):758-765. doi:10.3324/haematol.2011 This is an open-access paper. Citation: Wilson WH, Jung S-H, Porcu P, Hurd D, Johnson J, Martin SE, Czuczman M, Lai R, Said J, Chadburn A, Jones D, Dunleavy K, Canellos G, Zelenetz AD, Cheson BD, and Hsi ED for the Cancer and Leukemia Group B. A Cancer and Leukemia Group B multi-center study of DA-EPOCH-rituximab in untreated diffuse large B-cell lymphoma with analysis of outcome by molecular A Cancer and Leukemia Group B multi-center study of DA-EPOCH-rituximab

Key Points Higher allelic burden at day 21 of post-HCT is associated with higher risk of relapse and mortality. Longitudinal tracking of AML patients receiving HCT is feasible and provides clinically relevant information.

In order to evaluate feasibility of Sn-containing ferrous scrap recycling by evaporation of Sn, a number of liquid-gas experiments were carried out using an electromagnetic levitation melting technique. Rate of decrease of Sn concentration in liquid steel droplets by evaporation in Ar-H 2 gas mixture was determined at 1873 K (1600°C). Evaporation rate of the Sn under various conditions (various flow rates of the gas mixture, initial S concentration, [pct Sn] 0 ) was examined using previously reported rate equations. Increasing flow rate increased the evaporation rate of Sn initially, but the rate became constant at higher flow rate, which indicates that the rate-controlling step is the chemical reaction at the liquid/gas interface. Increasing initial S concentration significantly increased the evaporation rate of Sn, which is in good agreement with previous understanding that Sn could be evaporated as SnS(g). It was found in the present study that neither a simple first-order reaction (rate proportional to [pct Sn]) nor a second-order reaction (rate proportional to [pct Sn] 9 [pct S]) could account for the Sn evaporation under a chemical-reaction-controlled regime. It is proposed in the present study that surface adsorption of S should be taken into account in order to interpret the evaporation rate of Sn in such a way that S blocks available sites for SnS evaporation on the liquid steel. The ideal Langmuir isotherm was applied in order to better represent evaporation rate constant k SnS as a function of [pct S] (0.06 < [pct S] 0 < 0.29). The obtained rate constant of a reaction Sn i + S i = SnS i (g), k R SnS , is 2.57 9 10 À8 m 4 mol À1 s À1 .

To understand the effect of C on Sn evaporation from liquid iron in the view of ferrous scrap recycling, the evaporation of Sn from various liquid Fe-C-S-Sn alloys was experimentally investigated. A series of gas-liquid reactions was carried out at 1873 K (1600°C) using an electromagnetic levitation melting technique, where mass transfers in gas phase and liquid phase did not significantly affect the reaction rate. It was found that CS 2 (g) is a major gas species evaporating from Fe-C-S alloy (initial S content [pct S] 0 : 0.028 to 0.502 mass pct), and Fe-C-SSn alloy ([pct S] 0 : 0.063 to 0.560 mass pct), thereby competing with SnS for S in the liquid alloy. A model equation for the evaporation rate of CS 2 (g) was established using the experimental data for the Fe-C-S alloys. The chemical reaction rate constant for the CS 2 (g) evaporation (k R CS2 ) was obtained as 4.24 9 10 -12 m 7 mol -2 s -1 , and the residual rate constant (k r CS2 ) was 4.24 9 10 -16 m 7 mol -2 s -1 , both at 1873 K (1600°C). Roll of C on the evaporation of Sn in Fe-C-Sn alloy was confirmed to be the increase of activity coefficient of Sn. By taking into account (1) the evaporation of Sn(g), SnS(g), and CS 2 (g), and (2) the increasing activity coefficient of Sn and S by C, a comprehensive model for the evaporation rate of Sn and S in the Fe-C-Sn-S alloy was developed. The calculation results by the developed model in the present study showed good agreement with the experimental results. Some applications of the current model are presented in the view of increasing the Sn removal rate.

Several studies have suggested the possibility of a prognostic relationship between Epstein–Barr virus (EBV) and diffuse large B‐cell lymphoma (DLBCL). The clinical outcome of EBV‐associated DLBCL is not clear, especially since the introduction of rituximab. We retrospectively analyzed 222 elderly patients (≥50 years) with DLBCL who received R‐CHOP chemotherapy and evaluated the state of EBV‐encoded RNA‐1 (EBER). Eighteen cases (8.1%) were EBER‐positive (+). After a median of six cycles of R‐CHOP chemotherapy, the response rate (≥partial response) was 72.2% (13/18) in the EBV (+) patients and 90.2% (184/204) in the EBV (−) DLBCL patients (P = 0.021). Four of 18 (22.2%) EBV (+) DLBCL patients received two or fewer cycles of R‐CHOP chemotherapy. R‐CHOP chemotherapy was also interrupted early more frequently compared with the EBV (−) group (2.5%) (P = 0.00). At a median follow‐up of 32.8 months, there was no significant difference in the overall survival between the groups (P = 0.627). The EBV (+) DLBCL patients with early interruption of R‐CHOP chemotherapy showed a trend toward a high EBV‐DNA titer (≥1,000 copies/mL) (P = 0.091). The results suggest that the EBV (+) tumoral status of elderly DLBCL patients who undergo R‐CHOP chemotherapy does not predict their survival but that their EBV status may contribute to the early interruption of R‐CHOP chemotherapy. Am. J. Hematol. 88:774–779, 2013. © 2013 Wiley Periodicals, Inc.