Introduction Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA-EPOCH) was developed in an effort to overcome inadequate drug concentrations and to compensate for increased drug clearance. The goal of this study was to examine risk factors and outcomes in patients with aggressive non-Hodgkin lymphoma (aNHL) treated with DA-EPOCH. Patients and Methods We report 136 patients with previously untreated aNHL treated with infusional DA-EPOCH chemotherapy +/- rituximab from 2005-2013. Overall survival was estimated by Kaplan Meier methods. Univariate and multivariate logistic regression was used to determine factors associated with experiencing death, progression, or relapse at two years. Results The overall response rate was 82%. Relapse-free survival at 1, 3, and 5 years was 68%, 63%, and 52% with 95% CIs [0.59,0.85], [0.54,0.70], and [0.31,0.70], respectively. Patients with T-cell aNHL had increased risk of death, progression or relapse [OR:3.5, 95% CI: 1.4, 8.8] compared to those with B-cell aNHL. In multivariate analysis, current smoking, disease in the bone marrow and number of cycles completed were independent predictors of death or relapse. Conclusion Our data suggests EPOCH+/-R is active in both B and T-cell aNHL. Toxicity did not significantly delay treatment or negatively impact outcomes. Dose adjustment by hematopoietic nadir had no impact on outcomes. The impact of smoking during chemotherapy should be further evaluated.

Considerable research has been conducted on the effects of inter-institutional transfers, but far less consideration has been given to intra-institutional transfers and extended housing in off-habitat holding. On May 15, 2018, The Oregon Zoo’s orangutans (n = 3) were moved from the Red Ape Reserve (RAR) to the Veterinary Medical Center (VMC) indoor holding areas and remained there until December 22, 2020, resulting in over two years of housing in a facility not specifically designed for orangutans. This study aimed to quantify potential changes in fecal glucocorticoid metabolites (fGM) typically associated with increased adrenal activity as a result of transfers, as well as potential differences in fGM concentrations associated with housing in the two different types of locations. We collected fecal samples from all orangutans during three time periods: the initial housing at RAR (RAR1), the time spent at VMC holding (VMC), and the return to RAR (RAR2). Samples were analyzed using enzyme-immunoassay (EIA) analyses and compared using two-way ANOVA tests with Games–Howell post-hoc evaluations. The results of our analyses showed the following: (1) significant differences in fGM concentrations based on location in two orangutans, with the highest fGM concentration occurring in fecal samples collected at the VMC; and (2) a lack of significant fGM peaks following multiple intra-institutional transfers for all three orangutans. Though requiring further corroboration through future studies, we speculated that pre-transfer behavior training and intensive, continued care by familiar animal care staff may have helped to mitigate the stress responses commonly associated with transfers and major changes in housing. Furthermore, this study highlights the individualistic nature of the stress response, as illustrated by the substantial variation in fGM concentrations across different housing regimens in the three orangutans.

There are limited treatment modalities after high-grade gliomas recurrence. MGMT depletion modulated by dose-dense temozolomide (ddTMZ) remains a debated therapy for initial TMZ responders. Patients were selected retrospectively from our practice with diagnosis of high-grade gliomas (WHO grade III or IV), and were followed since the start of ddTMZ until death or change of therapy. Twenty-one patients were reviewed, with a median age of 47 (25-61) years and a median of 5.8 (1.5-38.8) cycles of ddTMZ. The majority were males (71.4%). Sixty-six percent received 21 on/28 off ddTMZ schedule, 28.6% daily, and 1 patient received a 7 days on/7 days off schedule. IDH mutation status was available for 18 (85.7%) patients, with 7 (33.3%) IDH mutant and 11 (52.5%) IDH wild type. MGMT methylation was assessed in 6 (28.6%) of the patients, being MGMT methylated in 3 (14.3%) patients, and non-methylated in 3 (14.3%) patients. The majority of patients (57.1%) were receiving ddTMZ in addition to other forms of therapy, including either bevacizumab (38.1%) or tumor-treating fields (TTFields) (19.1%). Overall ddTMZ was well tolerated, with few adverse events reported. The estimated median overall survival after ddTMZ start was 11 months. Median progression-free survival (PFS) was 6 months. Outcomes did not vary between patients receiving ddTMZ alone or those using TTFields or bevacizumab as concomitant therapy, but there was a trend to longer survival with the use of concomitant TTFields. Our results demonstrate benefit of ddTMZ after previous treatment with standard TMZ dosing with no apparent increase in treatment-related toxicities. In summary, ddTMZ should be considered in TMZ responsive patients and warrants further investigation.

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