Ipilimumab for Patients with Relapse after Allogeneic Transplantation

BACKGROUND: Loss of donor-mediated immune antitumor activity after allogeneic hematopoietic stem-cell transplantation (HSCT) permits relapse of hematologic cancers. We hypothesized that immune checkpoint blockade established by targeting cytotoxic T-lymphocyte–associated protein 4 with ipilimumab could restore antitumor reactivity through a graft-versus-tumor effect. METHODS: We conducted a phase 1/1b multicenter, investigator-initiated study to determine the safety and efficacy of ipilimumab in patients with relapsed hematologic cancer after allogeneic HSCT. Patients received induction therapy with ipilimumab at a dose of 3 or 10 mg per kilogram of body weight every 3 weeks for a total of 4 doses, with additional doses every 12 weeks for up to 60 weeks in patients who had a clinical benefit. RESULTS: A total of 28 patients were enrolled. Immune-related adverse events, including one death, were observed in 6 patients (21%), and graft-versus-host disease (GVHD) that precluded further administration of ipilimumab was observed in 4 patients (14%). No responses that met formal response criteria occurred in patients who received a dose of 3 mg per kilogram. Among 22 patients who received a dose of 10 mg per kilogram, 5 (23%) had a complete response, 2 (9%) had a partial response, and 6 (27%) had decreased tumor burden. Complete responses occurred in 4 patients with extramedullary acute myeloid leukemia and 1 patient with the myelodysplastic syndrome developing into acute myeloid leukemia. Four patients had a durable response for more than 1 year. Responses were associated with in situ infiltration of cytotoxic CD8+ T cells, decreased activation of regulatory T cells, and expansion of subpopulations of effector T cells in the blood. CONCLUSIONS: Our early-phase data showed that administration of ipilimumab was feasible in patients with recurrent hematologic cancers after allogeneic HSCT, although immune-mediated toxic effects and GVHD occurred. Durable responses were observed in association with several histologic subtypes of these cancers, including extramedullary acute myeloid leukemia. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01822509.

Tooth Color as a Predictor of Oral Health‐Related Quality of Life in Young Adults

PURPOSE: Smiling plays an important role in social interaction. The purpose of this research was to explore the extent to which objective parameters of color of one's own teeth affected the social and emotional dimensions of young adults' lives. MATERIALS AND METHODS: The sample included 134 subjects- students of the University of Rijeka, Croatia (65% female) aged 19 to 28 years (median 21). All subjects had six intact maxillary anterior teeth without restorations or severe malocclusions and healthy gingiva with no signs of inflammation. Tooth color was assessed intraorally using a spectrophotometer. Lightness, chroma, and translucency of the right maxillary central incisors (the reference teeth) were calculated and used for analysis. Subjects reported dimensions of their oral health-related quality of life (OHRQoL) using the Oral Health Impact Profile (OHIP), Orofacial Esthetic Scale (OES), and the Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ). Linear relationships between elements of tooth color and OHRQoL were explored using Pearson correlations. Multiple linear regression, while controlling for the influence of age and gender, was also calculated. ANOVA with a Tukey post hoc test was employed to test whether nonlinear relationships existed between OHRQoL and categories of color elements. RESULTS: Dental self-confidence, esthetic concerns, orofacial appearance, social impact and psychological impact were not related to lightness, chroma, or translucency of the subjects' teeth. Neither linear nor nonlinear relationships were detected between those aspects. Satisfaction with smile esthetics was only related to translucency where subjects with moderate translucency were least likely to be satisfied (p = 0.033). Women tended to report greater psychosocial impacts than men (p < 0.05), regardless of their tooth color. CONCLUSION: According to the results of this study objective, measurable, quantitative parameters of tooth color did not accurately predict psychosocial dimensions of OHRQoL in dentate young adults