BackgroundThe Women’s Interagency HIV Study was established in 1993 to study the natural history of HIV disease among women in the United States. It currently has enrolled 2,895 women testing positive for HIV infection and 972 women without HIV infection recruited from 6 national metropolitan locations. The clinical database information collected for each HIV-positive individual included CD4 cell counts, viral load, and antiviral treatment to evaluate HIV prognosis and related conditions in women.ObjectiveTo provide a baseline for fluconazole treatment prospects in women who test positive for HIV infection. As part of the ongoing Women’s Interagency HIV Study project, we investigated the fluconazole susceptibility of Candida spp. isolated from women with HIV in comparison to volunteer women without HIV. The implication of antifungal treatment on fluconazole susceptibility was evaluated by reviewing antifungal medication use for the past 2 years in each participant. In addition, genotyping of Candida spp. at oral and vaginal sites was monitored for 4 months in 9 patients.MethodsIn a cohort of 59 women with HIV and 24 women without HIV, colonization by Candida albicans and non-albicans species of the oral and vaginal sites was first determined. Fluconazole susceptibility was surveyed in vitro according to Clinical and Laboratory Standards Institute protocol. Antifungal drug treatment history was investigated for each patient to correspond with fluconazole susceptibility. Finally, series of isolates from several patients were followed for resistance and susceptibility. Their lineage was verified by genotyping multilocus sequence typing (MLST).ResultsA total of 280 Candida strains were recovered from oral and vaginal swabs of women with and without HIV infection. We found that patients with HIV were colonized with Candida spp. more frequently than women without HIV. The percent of isolates that were susceptibility dose dependent or resistant to fluconazole was higher in Candida glabrata compared with C. albicans isolates, but higher for C. albicans than other published data. Resistance was noted to be more common in vaginal sites. Fluconazole resistance in either species was not associated with relative CD4 cell counts or viral load. However an association with systemic application of fluconazole and resistance was noted.ConclusionsSystemic antifungal therapy, including a vaginal topical regimen in women with HIV infection correlated with reduced fluconazole susceptibility of oral and vaginal isolates. Genotype profiling has disclosed that a majority of isolates from the same individual are clustered together, suggesting the likelihood of an original strain with some microevolution. We observed a change from a susceptibility dose dependent to a resistant phenotype of isolates in 2 women with HIV infection, even though no treatments were received during the 4-month study and the prior 2 years.
Advanced cutaneous T cell lymphomas (CTCL) including mycosis fungoides (MF) and Sézary syndrome (SS) are often difficult to manage once they become resistant to initial systemic treatment. Current systemic treatments usually provide a limited duration of disease control, leaving this an area in desperate need of new treatment options for better long-term control. These conditions often affect the older population where transplantation may not be a feasible option. Recent studies evaluated a novel CCR4 humanized monoclonal antibody, mogamulizumab, in relapsed/refractory MF and SS, which show a meaningful progression free survival (PFS) benefit. In August 2018, mogamulizumab was approved by the FDA for the treatment of patients with relapsed/refractory MF/SS who have failed at least one treatment. Approval was based on the Phase III MAVORIC study comparing mogamulizumab to vorinostat, an FDA approved drug for this indication, in 372 patients. In this trial, mogamulizumab was found to have a superior PFS with a median of 7.7 months compared to 3.1 months in the vorinostat arm, with a hazard ratio of 0.53, p<0.001. Mogamulizumab was well tolerated with the most common AE being infusion-related reactions (32%), drug rash (20%), diarrhea (23%), and fatigue (22%). We reviewed the literature leading to the development and approval of mogamulizumab and suggest which patients may benefit the most from this treatment.
Mutations in the
FLT3
gene are associated with poor prognosis in patients with AML, even after consolidation with allogeneic hematopoietic cell transplantation (alloHCT) in first remission. Treatment failure in
FLT3
-mutated AML is largely driven by excessive risk of relapse compared to other genetic subtypes, including in patients post-alloHCT. As a result, there is substantial interest in studying posttransplant maintenance therapy in
FLT3
-mutated AML as an approach to optimize disease control and improve long-term outcomes. Clinical trials utilizing posttransplant FLT3 inhibitors, such as sorafenib and midostaurin, have shown feasibility, safety, and encouraging posttransplant outcomes, and there are ongoing studies using newer-generation tyrosine-kinase inhibitors as posttransplant maintenance therapy. Here, we review the toxicities and efficacy of FLT3 inhibitors as posttransplant maintenance, recommendations on the use of FLT3 inhibitors by international consensus guidelines, and highlight key remaining questions.
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