Poxvirus Vectored Cytomegalovirus Vaccine to Prevent Cytomegalovirus Viremia in Transplant Recipients: A Phase 2, Randomized Clinical Trial.

Background: Triplex vaccine was developed to enhance cytomegalovirus (CMV)-specific T cells and prevent CMV reactivation early after hematopoietic stem cell transplant (HCT). Objective: To determine the safety and efficacy of Triplex. Design: First-in-patient, phase 2 trial. (ClinicalTrials.gov: NCT02506933). Setting: 3 U.S. HCT centers. Participants: 102 CMV-seropositive HCT recipients at high risk for CMV reactivation. Intervention: Intramuscular injections of Triplex or placebo were given on days 28 and 56 after HCT. Triplex is a recombinant attenuated poxvirus (modified vaccinia Ankara) expressing immunodominant CMV antigens. Measurements: The primary outcomes were CMV events (CMV DNA level ≥1250 IU/mL, CMV viremia requiring antiviral treatment, or end-organ disease), nonrelapse mortality, and severe (grade 3 or 4) graft-versus-host disease (GVHD), all evaluated through 100 days after HCT, and grade 3 or 4 adverse events (AEs) within 2 weeks after vaccination that were probably or definitely attributable to injection. Results: A total of 102 patients (51 per group) received the first vaccination, and 91 (89.2%) received both vaccinations (46 Triplex and 45 placebo). Reactivation of CMV occurred in 5 Triplex (9.8%) and 10 placebo (19.6%) recipients (hazard ratio, 0.46 [95% CI, 0.16 to 1.4]; P = 0.075). No Triplex recipient died of nonrelapse causes during the first 100 days or had serious AEs, and no grade 3 or 4 AEs related to vaccination were observed within 2 weeks after vaccination. Incidence of severe acute GVHD after injection was similar between groups (hazard ratio, 1.1 [CI, 0.53 to 2.4]; P = 0.23). Levels of long-lasting, pp65-specific T cells with effector memory phenotype were significantly higher in Triplex than placebo recipients. Limitation: The lower-than-expected incidence of CMV events in the placebo group reduced the power of the trial. Conclusion: No vaccine-associated safety concerns were identified. Triplex elicited and amplified CMV-specific immune responses, and fewer Triplex-vaccinated patients had CMV viremia. Primary Funding Source: National Cancer Institute and Helocyte.

The association of hospital volume with rectal cancer surgery outcomes.

PURPOSE: An association between hospital volume and postoperative mortality has been identified for several oncologic surgical procedures. Our objective was to analyze differences in surgical outcomes for patients with rectal cancer according to hospital volume in the state of California. METHODS: A cross-sectional study from 2000 to 2005 was performed using the state of California Office of Statewide Health Planning and Development database. Hospitals were categorized into low (≤30)-, medium (31-60)-, and high (>60)-volume groups based on the total number of rectal cancer operations performed during the study period. RESULTS: Overall, 7,187 rectal cancer operations were performed. Of the 321 hospitals in the study cohort, 72 % (n = 232), 20 % (n = 65), and 8 % (n = 24) were low-, medium-, and high-volume hospitals, respectively. Postoperative mortality was significantly lower- in high-volume hospitals (0.9 %) when compared to medium- (1.1 %) and low-volume hospitals (2.1 %; p < 0.001). High-volume hospitals also performed more sphincter-preserving procedures (64 %) when compared to medium- (55 %) and low-volume hospitals (51 %; p < 0.001). CONCLUSIONS: These data indicate that hospital volume correlates with improved outcomes in rectal cancer surgery. Rectal cancer patients may benefit from lower mortality and increased sphincter preservation in higher-volume centers.

Long-Term Follow-Up of Multiple Myeloma Patients Treated with Tandem Autologous Transplantation Following Melphalan and Upon Recovery, Total Marrow Irradiation.

Total body irradiation in combination with melphalan for multiple myeloma (MM) has been shown to be prohibitively toxic. To ameliorate toxicity, total marrow irradiation (TMI) has been administered as the sole ablative modality during the second cycle of tandem autologous stem cell transplantation (TASCT) for MM patients on a phase I-II trial. Patients with MM in response or with stable disease and ≤18 months from diagnosis received melphalan 200 mg/m2 and autologous stem cell transplantation (ASCT) (cycle 1) and then, after recovery, TMI and another ASCT (cycle 2), followed by maintenance with an immunomodulatory drug (ImiD) and dexamethasone for up to 12 months. TMI doses were escalated from 1000 cGy to 1800 cGy in 200-cGy increments. Fifty-four patients were to receive TASCT between 2004 and 2011; 8 patients received single ASCT because of patient or physician preference. The median time between melphalan and TMI was 65 days (range, 47 to 125 days). Thirty patients (55.6%) underwent TASCT at the maximum tolerated dose of 1600 cGy. The complete response and very good partial response rates were 48.1% and 22.2%, respectively, following ASCT and maintenance. The median follow-up among survivors was 12.3 years (range, 9.2 to 15.5+ years). Progression-free survival (PFS) and overall survival at 10 years were 20.4% (95% confidence interval [CI], 10.9% to 31.9%) and 38.8% (95% CI, 25.9% to 51.5%), respectively. Secondary neoplasms included (1 each) acute myelogenous leukemia, papillary thyroid and prostate carcinoma, and melanoma, and there was 1 case of ductal carcinoma in situ and 4 cases of nonmelanoma skin cancers. TMI as part of TASCT was well tolerated, and TASCT was associated with a 20.4% PFS plateau. The inclusion of TMI as a conditioning regiment for MM before ASCT warrants further study in the context of modern induction and maintenance therapies.

Laparoscopic gastrojejunostomy in patients with obstruction of the gastric outlet secondary to advanced malignancies.

Surgical palliation is an important therapeutic goal in patients with gastric outlet obstruction from cancer. The use of laparoscopic approaches for this condition has not been well studied. Our objective is to compare surgical outcomes of laparoscopic and open gastrojejunostomies in patients with gastric outlet obstruction secondary to advanced malignancies. We did a retrospective review of 20 patients who underwent a palliative gastrojejunostomy as their primary surgical procedure. There were 10 patients in the laparoscopic group and 10 patients in the open one. We identified no significant difference between groups in mean surgery time (116 vs 116 minutes) (P = 0.99), blood loss (23 vs 142 mL) (P = 0.19), or length of stay (8 vs 14 days) (P = 0.14). We also identified no difference in median time to tolerate a regular diet (7 vs 8 days) (P = 0.49) and median survival (11.2 vs 9.0 months) (P = 0.83). Delayed gastric emptying was the most common complication occurring in four patients. There is no detectable difference in surgical outcomes between laparoscopic and open gastrojejunostomies in the management of patients with obstruction of the gastric outlet secondary to cancer. Laparoscopic gastrojejunostomy is a safe and feasible operation in this setting.

A phase 1/2 trial of high-dose yttrium-90-ibritumomab tiuxetan in combination with high-dose etoposide and cyclophosphamide followed by autologous stem cell transplantation in patients with poor-risk or relapsed non-Hodgkin lymphoma.

We conducted a phase 1/2 trial of high-dose 90Y-ibritumomab tiuxetan in combination with high-dose etoposide (VP-16) 40 to 60 mg/kg (day -4) and cyclophosphamide 100 mg/kg (day -2) followed by autologous stem cell transplantation (ASCT) in 31 patients with CD20+ non-Hodgkin lymphoma (NHL). Patients underwent dosimetry (day -21) with 5 mCi (185 MBq) 111In-ibritumomab tiuxetan following 250 mg/m2 rituximab, followed a week later by 90Y-ibritumomab tiuxetan to deliver a target dose of 1000 cGy to highest normal organ. Bone marrow biopsy was done on day -7 to estimate radiation dose and stem cells were reinfused when the radiation dose was estimated to be less than 5 cGy. The median 90Y-ibritumomab tiuxetan dose was 71.6 mCi (2649.2 MBq; range, 36.6-105 mCi; range, 1354.2-3885 MBq). Histology included follicular lymphoma (n = 12), diffuse large B-cell (n = 14), and mantle cell (n = 5). The median number of prior chemo-therapy treatments was 2. The treatment was well tolerated. The median times to reach an absolute neutrophil count greater than 500/microL and platelet count more than 20,000/microL were 10 days and 12 days, respectively. There were 2 deaths and 5 relapses. At a median follow-up of 22 months, the 2-year estimated overall survival and relapse-free survival rates are 92% and 78%, respectively. We conclude that high-dose 90Y-ibritumomab tiuxetan can be combined safely with high-dose etoposide and cyclophosphamide without an increase in transplant-related toxicity or delayed engraftment.