Carlos M. de Castro
Duke University
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Publication
Featured researches published by Carlos M. de Castro.
British Journal of Haematology | 2013
Peter Hillmen; Petra Muus; Alexander Röth; Modupe Elebute; Antonio M. Risitano; Hubert Schrezenmeier; Jeff Szer; Paul Browne; Jaroslaw P. Maciejewski; Jörg Schubert; Alvaro Urbano-Ispizua; Carlos M. de Castro; Gérard Socié; Robert A. Brodsky
Paroxysmal nocturnal haemoglobinuria (PNH) is characterized by chronic, uncontrolled complement activation resulting in elevated intravascular haemolysis and morbidities, including fatigue, dyspnoea, abdominal pain, pulmonary hypertension, thrombotic events (TEs) and chronic kidney disease (CKD). The long‐term safety and efficacy of eculizumab, a humanized monoclonal antibody that inhibits terminal complement activation, was investigated in 195 patients over 66 months. Four patient deaths were reported, all unrelated to treatment, resulting in a 3‐year survival estimate of 97·6%. All patients showed a reduction in lactate dehydrogenase levels, which was sustained over the course of treatment (median reduction of 86·9% at 36 months), reflecting inhibition of chronic haemolysis. TEs decreased by 81·8%, with 96·4% of patients remaining free of TEs. Patients also showed a time‐dependent improvement in renal function: 93·1% of patients exhibited improvement or stabilization in CKD score at 36 months. Transfusion independence increased by 90·0% from baseline, with the number of red blood cell units transfused decreasing by 54·7%. Eculizumab was well tolerated, with no evidence of cumulative toxicity and a decreasing occurrence of adverse events over time. Eculizumab has a substantial impact on the symptoms and complications of PNH and results a significant improvement in patient survival.
Blood | 2011
Dale J. Christensen; Youwei Chen; Jessica Oddo; Karen M. Matta; Jessica Neil; Evan D. Davis; Alicia D. Volkheimer; Mark C. Lanasa; Daphne R. Friedman; Barbara K. Goodman; Jon P. Gockerman; Louis F. Diehl; Carlos M. de Castro; Joseph O. Moore; Michael P. Vitek; J. Brice Weinberg
B-cell chronic lymphocytic leukemia (CLL), an incurable leukemia, is characterized by defective apoptosis. We found that the SET oncoprotein, a potent inhibitor of the protein phosphatase 2A (PP2A) tumor suppressor, is overexpressed in primary CLL cells and B-cell non-Hodgkin lymphoma (NHL) cell line cells. In CLL, increased levels of SET correlated significantly with disease severity (shorter time to treatment and overall survival). We developed SET antagonist peptides that bound SET, increased cellular PP2A activity, decreased Mcl-1 expression, and displayed selective cytotoxicity for CLL and NHL cells in vitro. In addition, shRNA for SET was cytotoxic for NHL cells in vitro. The SET antagonist peptide COG449 inhibited growth of NHL tumor xenografts in mice. These data demonstrate that SET is a new treatment target in B-cell malignancies and that SET antagonists represent novel agents for treatment of CLL and NHL.
Current Medical Research and Opinion | 2009
Jennifer R. Frytak; Henry J. Henk; Carlos M. de Castro; Rachel Halpern; Michael Nelson
ABSTRACT Objective: To examine the economic burden of myelodysplastic syndromes (MDS) and the incremental cost of transfusion dependence. Research design and methods: Adults with evidence of MDS were identified between 05/01/2000 and 09/30/2003 from a longitudinal, retrospective claims database for a large, geographically diverse US health plan and their medical histories were followed for at least 6 months. Patients were classified as transfusion-dependent (MDS-TD) or transfusion-independent (MDS-TI). Main outcome measures: Variables were categorized as demographic, health status, utilization, or cost. Utilization (inpatient hospitalizations, outpatient facility visits, emergency department visits, and physician office visits) is reported as the mean and median numbers of each specified encounter per subject. Costs were measured as the sum of patient and plan liability. All variables were analyzed descriptively, and appropriate statistical tests were used to compare the MDS-TD and MDS-TI cohorts. Pharmacy, medical, and total health care costs, adjusted for demographics and comorbidity, were estimated using gamma regression with a log link. Results: The MDS-TI cohort consisted of 2864 patients, and the MDS-TD cohort comprised 336 patients. Mean age for the entire study sample was 70.2 years. The MDS-TI cohort tended to receive most of its medical care at physicians’ offices, whereas the MDS-TD cohort received nearly as much medical care at outpatient facilities (e.g., infusion clinics, hospital outpatient clinics) as it did in physicians’ offices. The MDS-TD cohort had significantly higher mean annual costs: pharmacy,
Clinical Lymphoma, Myeloma & Leukemia | 2010
Anjali S. Advani; Mazyar Shadman; Francis Ali-Osman; Andrew Barker; Lisa Rybicki; Matt Kalaycio; Mikkael A. Sekeres; Carlos M. de Castro; Louis F. Diehl; Joseph O. Moore; Anne W. Beaven; Ed Copelan; Ronald Sobecks; Parisa Talea; David A. Rizzieri
4457 vs.
Cancer Investigation | 2013
Lauren Held; David A. Rizzieri; Gwynn D. Long; Jon P. Gockerman; Louis F. Diehl; Carlos M. de Castro; Joseph O. Moore; Mitchell E. Horwitz; Nelson J. Chao; Cristina Gasparetto
2926; medical,
American Journal of Hematology | 2015
Patrick T. Griffin; Rami S. Komrokji; Carlos M. de Castro; David A. Rizzieri; Magda Melchert; Alan F. List; Jeffrey E. Lancet
50,663 vs.
Biology of Blood and Marrow Transplantation | 2010
Cristina Gasparetto; Jon P. Gockerman; Louis F. Diehl; Carlos M. de Castro; Joseph O. Moore; Gwynn D. Long; Mitchell E. Horwitz; George P. Keogh; John P. Chute; Keith M. Sullivan; Rachel Neuwirth; Patricia H. Davis; Linda Sutton; Russell D. Anderson; Nelson J. Chao; David A. Rizzieri
17,469; total,
Cancer | 2009
David L. Grinblatt; Daohai Yu; Vera Hars; James W. Vardiman; Bayard L. Powell; Sreenivasa Nattam; Lewis R. Silverman; Carlos M. de Castro; Richard Stone; Clara D. Bloomfield; Richard A. Larson
51,066 vs.
Clinical Lymphoma, Myeloma & Leukemia | 2018
Benjamin Heyman; David A. Rizzieri; David J. Adams; Carlos M. de Castro; Louis F. Diehl; Zhiguo Li; Joseph O. Moore; Anne W. Beaven
19,811 (p < 0.001 for all comparisons). Thus, transfusion dependence was associated with an incremental cost of
Blood | 2008
Robert A. Brodsky; Neal S. Young; Elisabetta Antonioli; Antonio M. Risitano; Hubert Schrezenmeier; Jörg Schubert; Anna Gaya; Luke Coyle; Carlos M. de Castro; Chieh Lin Fu; Jaroslaw P. Maciejewski; Monica Bessler; Henk André Kroon; Russell P. Rother; Peter Hillmen
31,255 per patient per year. Some limitations inherent to using claims data and diagnosis codes for research apply to this study. Conclusions: This study demonstrated that an important consequence of transfusion dependence for MDS patients was markedly greater use of, and consequently higher costs associated with, inpatient and outpatient services. Continued research and efforts to develop biologic and pharmaceutical therapies may help more patients achieve transfusion independence, thereby reducing the financial burden of MDS.