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New Philadelphia, PA, United States

Pulte D.,German Cancer Research Center | Pulte D.,Cardeza Foundation for Hematologic Research | Redaniel M.T.,University of Bristol | Brenner H.,German Cancer Research Center | And 2 more authors.
Leukemia and Lymphoma | Year: 2014

Survival for patients with multiple myeloma has increased during the first decade of the 21st century. However, it is unknown whether the improvements in survival have extended equally in all ethnic groups. Using data from the United States Surveillance, Epidemiology and End Results Program, we assessed trends in survival and disease-related mortality for patients with myeloma by ethnic group, including non-Hispanic whites (nHw), African-Americans (AA), Hispanics and people of Asian and Pacific Islander descent (API) from 1998-2001 to 2006-2009. Overall, age adjusted 5-year relative survival increased, from 35.6% in 1998-2001 to 44% in 2006-2009. The greatest improvements were observed for patients aged 15-49, for whom survival increased by + 16.8% units for nHw and + 14.4% units for AA, whereas improvement was less pronounced and not statistically significant in Hispanics and API. Excess mortality hazard ratios were 1.20 (95% confidence interval [CI]: 1.09-1.33) for AA and 1.25 (95% CI: 1.11-1.41) for Hispanics compared to nHw in 2006-2009. Although survival increased greatly for nHw with myeloma between 1998-2001 and 2006-2009, smaller increases were observed for people of other ethnic groups. Persistent excess mortality was seen for AA and Hispanic patients with myeloma. Ethnic inequalities persisted or even increased from earlier periods to 2006-2009. The results suggest that ethnic minorities may not have benefited from newer treatments to the same extent as nHw patients have. © 2014 Informa UK, Ltd.

Edelstein L.C.,Cardeza Foundation for Hematologic Research | Simon L.M.,Baylor College of Medicine | Lindsay C.R.,Cardeza Foundation for Hematologic Research | Kong X.,Cardeza Foundation for Hematologic Research | And 10 more authors.
Blood | Year: 2014

Human platelets express 2 thrombin receptors: protease-activated receptor (PAR)-1 and PAR4. Recently, we reported 3.7-fold increased PAR4-mediated aggregation kinetics in platelets from black subjects compared with white subjects. We now show that platelets from blacks (n570) express 14% more PAR4 protein than those from whites (n584), but this difference is not associated with platelet PAR4 function. Quantitative trait locus analysis identified 3commonsingle nucleotide polymorphisms in thePAR4gene (F2RL3) associated with PAR4-induced platelet aggregation. Among these single nucleotide polymorphisms, rs773902 determines whether residue 120 in transmembrane domain 2 is an alanine (Ala) or threonine (Thr). Compared with the Ala120 variant, Thr120 was more common in black subjects than in white subjects (63% vs 19%), was associated with higher PAR4-induced human platelet aggregation and Ca21 flux, and generated greater inositol 1,4,5-triphosphate in transfected cells. A second, less frequent F2RL3 variant, Phe296Val, was only observed in blacks and abolished the enhanced PAR4-induced platelet aggregation and 1,4,5-triphosphate generation associated with PAR4-Thr120. PAR4 genotype did not affect vorapaxar inhibition of platelet PAR1 function, but a strong pharmacogenetic effect was observed with the PAR4-specific antagonist YD-3 [1-benzyl-3(ethoxycarbonylphenyl)-indazole]. These findings may have an important pharmacogenetic effect on the development of new PAR antagonists. © 2014 by The American Society of Hematology.

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