Important Considerations in the Diagnosis and Management of Post-transplant Lymphoproliferative Disorder.

PURPOSE OF REVIEW: A relative lack of molecular and clinical studies compared to other lymphoid cancers has historically made it difficult to determine optimal management approaches in post-transplant lymphoproliferative disorder (PTLD). We sought to better define the "state of the science" in PTLD by examining recent advances in risk assessment, genomic profiling, and trials of PTLD-directed therapy. RECENT FINDINGS: Several major clinical trials highlight risk-stratified sequential therapy incorporating rituximab with or without chemotherapy as a rational treatment strategy in patients with CD20+ PTLD who do not respond to reduction of immunosuppression alone. Epstein Barr virus (EBV)-targeted cytotoxic lymphocytes are a promising approach in patients with relapsed/refractory EBV+ PTLD, but dedicated clinical trials should determine how autologous chimeric antigen receptor T cell therapy (CAR-T) may be safely administered to PTLD patients. Sequencing studies underscore the important effect of EBV infection on PTLD pathogenesis, but comprehensive genomic and tumor microenvironment profiling are needed to identify biomarkers that predict response to treatment in this clinically heterogeneous disease.

Secondary Central Nervous System Lymphoma: Updates in Treatment and Prophylaxis Strategies.

OPINION STATEMENT: Referring to any central nervous system (CNS) involvement with preceding or concurrent systemic disease, secondary CNS lymphoma (SCNSL) lacks a clear standard of care and historically carries a very poor prognosis. Aggressive histologies predominate, most notably diffuse large B cell lymphoma (DLBCL), with higher relative frequency in Burkitt lymphoma but lower absolute incidence. Therapeutic strategies commonly feature intensive CNS-penetrant chemotherapy, including methotrexate, cytarabine, and others. Combination regimens, novel targeted agents, and cellular therapy considerations are reviewed, noting that patients with SCNSL are often excluded from clinical trials and dedicated SCNSL studies are historically limited. Given these challenges, there has been renewed attention on CNS prophylaxis as well as strategies for early CNS detection. Prophylaxis is standard of care in Burkitt lymphoma, whereas its role in DLBCL and related histologies is increasingly unclear.

A Systematic Review of Intravaginal Diazepam for the Treatment of Pelvic Floor Hypertonic Disorder.

This systematic review evaluates the efficacy of intravaginal diazepam in treating chronic pelvic pain and sexual dysfunction associated with high-tone pelvic floor dysfunction. A literature search was conducted in Medline and Web of Science, including articles from the database's inception to July 2019. The search identified 126 articles, and 5 articles met study inclusion criteria: 2 observational reviews and 3 small randomized, controlled trials (RCTs) evaluating intravaginal diazepam for high-tone pelvic floor dysfunction. The 2 observational studies identified subjective reports of improvement in sexual function for a majority of women, 96% and 71%, in each study. However, there were no statistical differences between Female Sexual Function Index (FSFI) and Visual Analog Scale (VAS) scores for pain identified. One RCT found no significant changes between groups in median FSFI or VAS scores, and a second RCT found no significant changes between groups in 100-mm VAS scores. The third RCT demonstrated that compared with placebo, treatment with transcutaneous electrical nerve stimulation and intravaginal diazepam for women with vestibulodynia and high-tone pelvic floor dysfunction yielded significant differences in reduction of dyspareunia (P ≤ .05), ability to relax pelvic floor muscles after contraction (P ≤.05), and current perception threshold values at a 5-Hz stimulation related to C fibers (P < .05), but no significant changes in 10-cm VAS scores. Intravaginal diazepam may be helpful in women with a specific diagnosis of high-tone pelvic floor dysfunction, but more and larger studies are needed to confirm these potential effects.

Safety and efficacy of extended dosing intervals of denosumab in patients with solid cancers and bone metastases: a retrospective study.

AIM: More than half of patients with breast, lung, or prostate cancer who have bone metastases have evidence of skeletal-related events (SREs). Denosumab is a fully human monoclonal antibody that binds to and neutralizes receptor activator of nuclear factor kappa-B ligand (RANKL) on osteoblasts and their precursors. The United States Food and Drug Administration (FDA)-approved dose of denosumab is 120 mg every 4 weeks; however, other schedules have been used in practice for patient convenience. Evidence for the safety and efficacy of alternative dosing intervals is lacking. PATIENT & METHODS: Adult patients with solid cancers and bone metastases who received at least two doses of denosumab 120 mg were reviewed. Patients were grouped based on an average denosumab dosing interval of <5 weeks (short-interval) versus 5-11 weeks (medium-interval) versus ⩾12 weeks (long-interval). The primary outcome was the time to first SRE while on denosumab between the short- and medium-interval groups. The secondary outcomes were overall survival (OS), efficacy comparisons between the other groups, and safety events. RESULTS: There was no significant difference in median time to first SRE between the short- and medium-interval denosumab groups [33.2 versus 28.4 months, hazard ratio (HR): 1.13, 95% confidence interval (CI): 0.66-1.92, p = 0.91] or the medium- and long-interval dosing groups (28.4 versus 32.2 months, HR: 1.15, 95% CI: 0.66-2.01, p = 0.62). Median OS was not found to differ significantly between any of the groups. There were significantly more hospitalizations in the short-interval dosing group than the other groups (55.2% versus 33.8% versus 30.4%, p < 0.001). CONCLUSION: Extending denosumab dosing intervals does not appear to negatively impact time to first SRE and is associated with fewer hospitalizations in real-world patients with solid cancers and bone metastases.