RESUMEN
Current safety data affirms enzalutamide does not cause clinically significant liver dysfunction that warrant therapy cessation. Therefore, clinicians should not withhold potentially successful therapy merely for suspected hepatotoxicity or PnC.
RESUMEN
Infusing natural killer (NK) cells following transplantation may allow less infections and relapse with little risk of acute graft-versus-host disease (aGVHD). We delivered 51 total NK cell-enriched donor lymphocyte infusions (DLIs) to 30 patients following a 3-6/6 HLA matched T cell-depleted nonmyeloablative allogeneic transplant. The primary endpoint of this study was feasibility and safety. Eight weeks following transplantation, donor NK cell-enriched DLIs were processed using a CD56(+) selecting column with up to 3 fresh infusions allowed. Toxicity, relapse, and survival were monitored. T cell phenotype, NK cell functional recovery, and KIR typing were assessed for association with outcomes. Fourteen matched and 16 mismatched transplanted patients received a total of 51 NK cell-enriched DLIs. Selection resulted in 96% (standard deviation [SD] 8%) purity and 83% (SD 21%) yield in the matched setting and 97% (SD 3%) purity and 77% (SD 24%) yield in the mismatched setting. The median number of CD3(-) CD56(+) NK cells infused was 10.6 (SD 7.91) x 10(6) cells/kg and 9.21 (SD 5.6) x 10(6) cells/kg, respectively. The median number of contaminating CD3(+)CD56(-) T cells infused was .53 (1.1) x 10(6) and .27 (.78) x 10(6) in the matched and mismatched setting, respectively. Only 1 patient each in the matched (n = 14) or mismatched (n = 16) setting experienced severe aGVHD with little other toxicity attributable to the infusions. Long-term responders with multiple NK cell-enriched infusions and improved T cell phenotypic recovery had improved duration of responses (p = .0045) and overall survival (OS) (P = .0058). A 1-step, high-yield process is feasible, and results in high doses of NK cells infused with little toxicity. NK cell-enriched DLIs result in improved immune recovery and outcomes for some. Future studies must assess whether the improved outcomes are the direct result of the high doses and improved NK cell function or other aspects of immune recovery.
Asunto(s)
Antígenos HLA/inmunología , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/trasplante , Trasplante de Células Madre/métodos , Adulto , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Transfusión de Linfocitos/métodos , Linfocitos/inmunología , Donantes de Tejidos , Acondicionamiento Pretrasplante/métodos , Trasplante HomólogoRESUMEN
A substantial increase in the number of elderly people in the populations of developed nations in the coming years has been projected. Persons 65 years and older are at significantly higher risk of developing cancer when compared to younger individuals. There is a resulting increase in cancer incidence as well as mortality in this advanced age group. It is important to know how changes in physiological reserve and functional status in elderly patients, polypharmacy issues, comorbidities, and other age-related problems can affect cancer prognosis and management. Elderly patients are not adequately represented in clinical trials, thus creating a relative lack of information related to specific issues about elderly cancer patients and their care. Nevertheless, there is a substantial amount of guidance available, and in this review we will address selected issues of importance when considering the approach to the older cancer patient.
