IdeS (Imlifidase): A Novel Agent That Cleaves Human IgG and Permits Successful Kidney Transplantation Across High-strength Donor-specific Antibody.

OBJECTIVES: The presence of a donor-specific positive crossmatch has been considered to be a contraindication to kidney transplantation because of the risk of hyperacute rejection. Desensitization is the process of removing hazardous preformed donor-specific antibody (DSA) in order to safely proceed with transplant. Traditionally, this involves plasmapheresis and intravenous immune globulin treatments that occur over days to weeks, and has been feasible when there is a living donor and the date of the transplant is known, allowing time for pre-emptive treatments. For sensitized patients without a living donor, transplantation has been historically difficult. SUMMARY OF BACKGROUND DATA: IdeS (imlifidase) is an endopeptidase derived from Streptococcus pyogenes which has specificity for human IgG, and when infused intravenously results in rapid cleavage of IgG. METHODS: Here we present our single-center's experience with 7 highly sensitized (cPRA98-100%) kidney transplant candidates who had DSA resulting in positive crossmatches with their donors (5 deceased, 2 living) who received IdeS within 24 hours prior to transplant. RESULTS: All pre-IdeS crossmatches were positive and would have been prohibitive for transplantation. All crossmatches became negative post-IdeS and the patients underwent successful transplantation. Three patients had DSA rebound and antibody-mediated rejection, which responded to standard of care therapies. Three patients had delayed graft function, which ultimately resolved. No serious adverse events were associated with IdeS. All patients have functioning renal allografts at a median follow-up of 235 days. CONCLUSION: IdeS may represent a groundbreaking new method of desensitization for patients who otherwise might have no hope for receiving a lifesaving transplant.

Primary lymphoma of bone in adult patients.

BACKGROUND: The low incidence of primary lymphoma of bone (PLB) has led to discrepancies in classification as well as difficulty in prognostication. The authors of this report used the Surveillance, Epidemiology, and End Results (SEER) database to analyze a large, population-based cohort of adult patients with this disease. The database provides a standardized classification and documentation of outcomes and enables a meaningful evaluation of prognostic factors. METHODS: The SEER database was used to identify all patients who were diagnosed with PLB from 1973 through 2005. Survival was analyzed with the Kaplan-Meier method, and the influence of clinical parameters on survival was analyzed with the log-rank test. A Cox proportional hazards model was used for multivariate analysis. RESULTS: Fifteen hundred adult patients with PLB were analyzed. The 5-year and 10-year survival rates for adult patients were 58% and 45%, respectively. Multivariate analysis revealed that younger age and localized disease were independent predictors of survival. It is noteworthy that the incidence of disease, as determined by the annual percentage change, increased during the study period (P < .05). CONCLUSIONS: This analysis of a large cohort of adults with PLB indicated that the only identifiable prognostic indicators were localized disease and younger age. The authors concluded that future treatment for patients with PLB need to be based on strict staging criteria and adherence to successful published protocols using collaborative clinical trials.

Ewing sarcoma demonstrates racial disparities in incidence-related and sex-related differences in outcome: an analysis of 1631 cases from the SEER database, 1973-2005.

BACKGROUND: Previous reports of Ewing sarcoma cohorts suggested that there is a difference in incidence according to racial origin. However, to the authors' knowledge, this finding has never been tested in a population-based database, and the impact of race on clinical outcome and the significance of known risk factors stratified to racial groups have not been reported. METHODS: Patients who had Ewing sarcoma diagnosed between 1973 and 2005 were identified in the Surveillance, Epidemiology, and End Results database. Patient demographic and clinical characteristics; incidence; year of diagnosis; tumor location, tumor size, and disease stage at diagnosis; treatment(s); cause of death; and survival were extracted. Kaplan-Meier, log-rank, and Cox regressions were used to analyze the significance of prognostic factors. RESULTS: Race-specific incidence indicated that Caucasians have the highest incidence (0.155), followed by Asians/Pacific Islanders (0.082), and African Americans (0.017). The difference in incidence between Caucasians and African Americans was 9-fold and significant (P<.001). The incidence of Ewing sarcoma increased over the past 3 decades among Caucasians (P<.05). Survival was not impacted by race. Local disease stage, primary tumor location in the appendicular skeleton, and tumor size

Prognostic factors for survival in patients with epithelioid sarcoma: 441 cases from the SEER database.

UNLABELLED: Current stratification of prognosis in patients with epithelioid sarcoma (ES) is based largely on data reported by individual centers with a limited number of patients. We sought to identify the important prognostic parameters using the Surveillance, Epidemiology, and End Results (SEER) database. We identified 441 patients with ES in the database and extracted information regarding patient demographics and clinical characteristics. Kaplan-Meier, log-rank, and Cox regression were used for analysis. Disease-specific survival declined until 100 months after diagnosis after which survival was unrelated to epithelioid sarcoma. The overall incidence of ES during 2005 was 0.041 per 100,000. The reported incidence has increased since 1973, with an annual percentage change of 5.217%. On multivariate analysis, only age younger than 16 years, local stage of disease, or negative nodes and surgical resection of the tumor predicted better disease-specific survival. We observed no increase in survival by comparing decades of diagnosis since 1986. The SEER database shows only age younger than 16 years, negative nodes, or local stage of disease and operability of primary disease independently predict survival in patients with ES. LEVEL OF EVIDENCE: Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.