Brentuximab vedotin in CD30+ primary cutaneous T-cell lymphomas: a review and analysis of existing data.

BACKGROUND: The utility of brentuximab vedotin (BV) in CD30+ systemic lymphomas is established, however evidence for treating primary cutaneous lymphoma remains limited. This study aimed to evaluate BV in treating CD30+ transformed mycosis fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (PC-ALCL). METHODS: A literature review was conducted, and we analyzed data from published trials and case reports obtained via search of Ovid-MEDLINE® and PubMed databases. The search yielded 372 reports, and 10 publications met inclusion criteria. Sixty-one patients with CD30+ transformed MF and seven with PC-ALCL were included. RESULTS: Mean age at BV initiation was 60.8 years (67 - PC-ALCL; 60.1 - MF), and 4.1 therapies were attempted prior to BV (3.1 - PC-ALCL; 4.2 - MF). The overall response rate was 67.7% (100% - PC-ALCL; 63.9% - MF), with 16.2% of patients experiencing complete response (100% - PC-ALCL; 6.6% - MF). Mean time to clinical response was 5.3 and 9.3 weeks for PC-ALCL and MF, respectively. Mean response duration for patients with PC-ALCL was 7.6 and 7.8 months for MF. Peripheral neuropathy (57.2%) and fatigue (35.6%) were the most commonly reported adverse effects. CONCLUSIONS: This analysis summates the current evidence regarding the use of BV in treating CD30+ MF and PC-ALCL. Preliminary results indicate that BV is effective for CD30+ CTCL, however additional studies with larger sample sizes are necessary. The study provides clinicians with the clinical context in which BV may be appropriate as well as information regarding therapeutic expectations and outcomes.

Myeloid-Derived Suppressor Cells in Psoriasis Are an Expanded Population Exhibiting Diverse T-Cell-Suppressor Mechanisms.

Psoriasis vulgaris is an inflammatory skin disease caused by hyperactivated T cells regulated by positive and negative mechanisms; although the former have been much studied, the latter have not. We studied the regulatory mechanism mediated by myeloid-derived suppressor cells (MDSCs) and showed that MDSCs expanded in melanoma patients express dendritic cell-associated heparan sulfate proteoglycan-dependent integrin ligand, a critical mediator of T-cell suppressor function. We examined expansion of DC-HIL(+) MDSCs in psoriasis and characterized their functional properties. Frequency of DC-HIL(+) monocytic MDSCs (CD14(+)HLA-DR(no/low)) in blood and skin was markedly increased in psoriatic patients versus healthy control subjects, but there was no statistically significant relationship with disease severity (based on Psoriasis Area and Severity Index score). Blood DC-HIL(+) MDSC levels in untreated patients were significantly higher than in treated patients. Compared with melanoma-derived MDSCs, psoriatic MDSCs exhibited significantly reduced suppressor function and were less dependent on DC-HIL, but they were capable of inhibiting proliferation and IFN-γ and IL-17 responses of autologous T cells. Psoriatic MDSCs were functionally diverse among patients in their ability to suppress allogeneic T cells and in the use of either IL-17/arginase I or IFN-γ/inducible nitric oxide synthase axis as suppressor mechanisms. Thus, DC-HIL(+) MDSCs are expanded in psoriasis patients, and their mechanistic heterogeneity and relative functional deficiency may contribute to the development of psoriasis.

The Northern California Chronic Care Network for Dementia.

The Northern California Chronic Care Network for Dementia brings together Northern California's major providers of managed care, community-based care, consumer education, and advocacy in new partnerships to improve the care of persons with dementia enrolled in managed care plans and their family caregivers. These partnerships are part of a national initiative entitled the Chronic Care Network for Alzheimer's Disease (CCN/AD) sponsored by the National Chronic Care Consortium and the Alzheimer's Association. This initiative selected eight promising provider-consumer partnerships across the country to implement and evaluate a new model of coordinated care for people with dementia and their families. This paper describes the Northern California network's partnerships and its intervention and challenges. The intervention is grounded in the key components of the CCN/AD model: "identification of patients with possible dementia, diagnostic assessment, care management and family caregiver information and support." These components, in turn, are translated into protocols and pathways designed to create timely, comprehensive, appropriate, and effective systems of care services that address the unique needs of dementia patients and their caregivers over the course of the disease.