Maintenance rituximab or observation after frontline treatment with bendamustine-rituximab for follicular lymphoma.

Bendamustine (B) with rituximab (R) is a standard frontline treatment for medically fit follicular lymphoma (FL) patients. The safety and efficacy of maintenance rituximab (MR) after BR induction has not been formally compared to observation for FL, resulting in disparate practice patterns. Prospective trials have shown benefit of MR after R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or R-CVP (rituximab, cyclophosphamide, vincristine, prednisone), yet recent data from the GALLIUM study comparing outcomes of patients treated with chemotherapy with R or obinutuzumab (G) showed higher than anticipated fatal adverse events with BR/BG. In order to assess the efficacy and tolerability of MR after BR, we retrospectively collected data on 640 newly diagnosed patients treated with FL. We found that patients who achieved partial remission (PR) after ≥4 cycles of BR had improved duration of response (DOR) with MR vs. no maintenance, whereas those in complete remission did not. These findings were confirmed in a validation cohort. In the entire study population, the known fatal adverse event rate after BR was 2·5% and did not significantly differ in those receiving MR versus no maintenance. [Correction added on 14 January 2019, after online publication: The preceding sentence has been corrected in this current version.] Within the limitations inherent to retrospective analysis, these data suggest that FL patients with a PR to BR experience prolongation of remission with MR with an acceptable safety profile.

Clinicopathologic Findings in Patients With Initial Diagnosis of Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue (MALT) in Colorectal Mucosa.

OBJECTIVES: To evaluate clinicopathologic features, management, and behavior of colorectal extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT). METHODS: Clinical data, laboratory studies, and radiographic records were reviewed (2005-2018), and fluorescence in situ hybridization studies were performed. RESULTS: Eleven patients were identified, six of whom were discovered as an incidental finding on endoscopy. Morphologic and immunophenotypic features were similar to MALT lymphomas at other sites except that lymphoepithelial lesions were uncommon. Three of nine patients were positive for BIRC3/MALT1 fusions, two of whom had identical B-cell clones identified in subsequent gastric biopsy specimens. Eight of 10 patients had no clinically evaluable disease after observation (±antibiotics; n = 4) or radiation/chemotherapy (n = 4). CONCLUSIONS: Patients with incidental and localized colonic MALT lymphoma demonstrated an excellent prognosis with conservative management, although longer follow-up and data based on consistent staging and surveillance methods (including gastric evaluation) are necessary for informed management.

Modified VR-CAP, Alternating With Rituximab and High-dose Cytarabine: An Effective Pre-transplant Induction Regimen for Mantle Cell Lymphoma.

BACKGROUND: Initial treatment of mantle cell lymphoma (MCL) incorporating autologous stem cell transplantation affords long-term remissions, but relapses still occur. Optimal pretransplant therapy will afford high complete response rates and not impair stem cell collection. Incorporation of bortezomib represents a natural evolution of pretransplant therapy, given its proven first-line efficacy and minimal impact on stem cell collection. PATIENTS AND METHODS: At the University of Washington/Seattle Cancer Care Alliance and the Cleveland Clinic Foundation, we developed modified VR-CAP/R+ara-C (bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone, alternating with rituximab and high-dose cytarabine), for transplant-eligible patients with MCL. This regimen was administered as standard-of-care, pretransplant therapy to consecutive patients with MCL from April 2015 to the present. RESULTS: A total of 37 patients were treated with this regimen, including 18 at the University of Washington/Seattle Cancer Care Alliance and 19 at the Cleveland Clinic Foundation. Most patients had intermediate- or high-risk disease by both (mantle-cell lymphoma international prognostic index (MIPI)-B and MIPI-C category. Complete response to induction was achieved in 32 (86%) of 37 evaluable patients; 2 achieved partial response, and 3 had primary refractory disease. Stem cell collection was successful in 1 attempt in 30 of 32 patients. The median follow-up of survivors measured from start of treatment is 17.4 months. Five patients have progressed, and 4 have died (2 owing to lymphoma, 2 from toxicity). CONCLUSION: Modified VR-CAP/R+ara-C is feasible pretransplant therapy for patients with MCL and is associated with a high rate of complete response and eligibility for autologous stem cell transplantation.

Viscoelastic diamine surfactant for stable carbon dioxide/water foams over a wide range in salinity and temperature.

HYPOTHESIS: The viscosity and stability of CO2/water foams at elevated temperature can be increased significantly with highly viscoelastic aqueous lamellae. The slow thinning of these viscoelastic lamellae leads to greater foam stability upon slowing down Ostwald ripening and coalescence. In the aqueous phase, the viscoelasticity may be increased by increasing the surfactant tail length to form more entangled micelles even at high temperatures and salinity. EXPERIMENTS: Systematic measurements of the steady state shear viscosity of aqueous solutions of the diamine surfactant (C16-18N(CH3)C3N(CH3)2) were conducted at varying surfactant concentrations and salinity to determine the parameters for formation of entangled wormlike micelles. The apparent viscosity and stability of CO2/water foams were compared for systems with viscoelastic entangled micellar aqueous phases relative to those with much less viscous spherical micelles. FINDINGS: We demonstrated for the first time stable CO2/water foams at temperatures up to 120 °C and CO2 volumetric fractions up to 0.98 with a single diamine surfactant, C16-18N(CH3)C3N(CH3)2. The foam stability was increased by increasing the packing parameter of the surfactant with a long tail and methyl substitution on the amine to form entangled viscoelastic wormlike micelles in the aqueous phase. The foam was more viscous and stable compared to foams with spherical micelles in the aqueous lamellae as seen with C12-14N(EO)2 and C16-18N(EO)C3N(EO)2.

Pegylated GCSF Can Be Used With First-Line da-EPOCH-R Without Compromising Dose Intensity, Safety, or Efficacy.

INTRODUCTION: Infusional da-EPOCH-R (dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab) is a dose-intensified regimen with a potential role in treating high-risk subtypes of aggressive B-cell non-Hodgkin lymphoma (B-NHL). Studies of da-EPOCH-R use daily injections of granulocyte colony-stimulating factor (GCSF) to tailor chemotherapy dosing, and whether 1-time administration of pegylated GCSF (peg-GCSF) is as efficacious has not been addressed. PATIENTS AND METHODS: We reviewed aggressive B-NHL patients treated at our center with first-line da-EPOCH-R for clinician choice of growth factor, and analyzed dose level achieved, rate of unplanned hospitalizations, and patient outcomes. RESULTS: Among 73 patients, 44 received peg-GCSF. Overall, 11 patients (15%) patients achieved dose level 4. Baseline characteristics between peg-GCSF and GCSF groups were similar. The proportion of patients who achieved dose level 4 was comparable in the peg-GCSF group (5 of 44 [11%]) and daily GCSF (6 of 29 [21%]; P = .24). The rate of unplanned hospitalizations, and event-free and overall survival, were also similar between groups. CONCLUSION: We suggest routine use of peg-GCSF is an acceptable alternative to daily GCSF, for patients in whom da-EPOCH-R is selected as first-line treatment for aggressive B-NHL.

Phase behavior and interfacial properties of a switchable ethoxylated amine surfactant at high temperature and effects on CO2-in-water foams.

The interfacial properties for surfactants at the supercritical CO2-water (C-W) interface at temperatures above 80°C have very rarely been reported given limitations in surfactant solubility and chemical stability. These limitations, along with the weak solvent strength of CO2, make it challenging to design surfactants that adsorb at the C-W interface, despite the interest in CO2-in-water (C/W) foams (also referred to as macroemulsions). Herein, we examine the thermodynamic, interfacial and rheological properties of the surfactant C12-14N(EO)2 in systems containing brine and/or supercritical CO2 at elevated temperatures and pressures. Because the surfactant is switchable from the nonionic state to the protonated cationic state as the pH is lowered over a wide range in temperature, it is readily soluble in brine in the cationic state below pH 5.5, even up to 120°C, and also in supercritical CO2 in the nonionic state. As a consequence of the affinity for both phases, the surfactant adsorption at the CO2-water interface was high, with an area of 207Å(2)/molecule. Remarkably, the surfactant lowered the interfacial tension (IFT) down to ∼5mN/m at 120°C and 3400 psia (23MPa), despite the low CO2 density of 0.48g/ml, indicating sufficient solvation of the surfactant tails. The phase behavior and interfacial properties of the surfactant in the cationic form were favorable for the formation and stabilization of bulk C/W foam at high temperature and high salinity. Additionally, in a 1.2 Darcy glass bead pack at 120°C, a very high foam apparent viscosity of 146 cP was observed at low interstitial velocities given the low degree of shear thinning. For a calcium carbonate pack, C/W foam was formed upon addition of Ca(2+) and Mg(2+) in the feed brine to keep the pH below 4, by the common ion effect, in order to sufficiently protonate the surfactant. The ability to form C/W foams at high temperatures is of interest for a variety of applications in chemical synthesis, separations, materials science, and subsurface energy production.