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1. CLIN-NEURO-COGNITIVE

Author

J. L. Scotland, I. R. Whittle, I. J. Deary, E. K. De Witte, P. Marien, R. Jalali, V. Kothawade, T. Gupta, S. Goswami, J. Swamidas, C. A. Racine, J. M. Lupo, A. Molinaro, A. Parks, S. M. Chang, M. S. Berger, N. Butowski, C. Linville, R. Hampson, S. Deadwyler, A. Peiffer, K. B. Peters, S. Woodring, J. E. Herndon, F. McSherry, J. J. Vredenburgh, A. Desjardins, H. S. Friedman, J. S. Wefel, S. Shook, P. D. Brown, N. N. Laack, A. Choucair, J. H. Suh, D. Roberge, V. Kavadi, M. P. Mehta, D. Watkins-Bruner, C. Weiss, C. Nettekoven, V. Neuschmelting, A. Eisenbeis, A. Rehme, C. Grefkes, R. Goldbrunner, A. M. Peiffer, D. Case, E. G. Shaw, S. Rapp, S. Ambert-Pompey, N. D. Doolittle, C. Lacy, R. Fu, R. W. Butler, C. Varallyay, E. A. Neuwelt, A. Jakary, and S. J. Nelson

Subjects
Cancer Research, medicine.medical_specialty, business.industry, Trail Making Test, Controlled Oral Word Association Test, Cognition, National Adult Reading Test, Abstracts, Cognitive epidemiology, Oncology, Cohort, Physical therapy, Medicine, Verbal fluency test, Neurology (clinical), business, Neurocognitive
Abstract

CLIN-NEURO-COGNITIVE NC-02. ASSESSING NEURO-COGNITIVE STATUS IN NEWLY PRESENTING PATIENTS WITH SUPRATENTORIAL INTRACRANIAL TUMOURS. Jennifer L. Scotland1, Ian R. Whittle1, and Ian J. Deary2; University of Edinburgh, Edinburgh, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, Dept. of Psychology, University of Edinburgh, Edinburgh, United Kingdom INTRODUCTION: Neurocognitive endpoints are increasingly included in clinical trials in neuro-oncological settings (Meyers & Brown, 2006). There is a need to identify short, repeatable measures of cognition that are sensitive to impairment in this group. Previous authors have proposed such batteries. METHODS: Newly presenting patients with a radiological diagnosis of any intracranial tumour (n 1⁄4 118) were assessed, prior to any surgical intervention, on a number of standardised cognitive and other measures as part of a larger study (Scotland et al., 2012). Their performance was compared with that of patients admitted for elective spinal surgery (n 1⁄4 85) and a healthy control group (n 1⁄4 80). RESULTS: Analysis of covariance compared the performance of the three groups. Age, sex, and National Adult Reading Test score (used to assess premorbid function) were the covariates. Patients with intracranial tumours performed significantly worse on the majority of the tests. The intracranial tumour cohort had significantly lower scores than did the spinal surgery and healthy control groups on the following measures: immediate and delayed memory (Rey Auditory Verbal Learning Test, RAVLT; p , 0.001); Trail Making Test Part B (p , 0.001); digit-symbol coding (p , 0.001); and verbal fluency (Controlled Oral Word Association Test, COWAT; p 1⁄4 0.002 and p , 0.001, respectively). There was a moderate-to-large effect size in the participant group for all tests. DISCUSSION/CONCLUSIONS: The RAVLT, Trail Making Test Part B, and COWAT are sensitive measures of cognitive impairment in patients with brain tumours and support Meyers & Brown’s (2006) proposal for the inclusion of these tests in clinical trials that have neurocognitive endpoints. The verbal fluency test, in particular, has a number of potential advantages for use in neuro-oncological settings, given that it can be completed by patients with focal motor deficits and is available in alternate forms to reduce practice effects. NC-03. A STANDARD NEUROLINGUISTIC APPROACH TO

Published
2012
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2. Neuro-cognitive

Author

S. H. O'Neil, J. Azoff, C. Buranahirun, G. Dhall, A. Panigrahy, M. Borchert, S. Khatua, L. Ji, R. Sposto, J. Finlay, X. Gong, P. Schwartz, M. Linskey, D. A. Bota, J. S. Wefel, S. Y. Patwardhan, C. Strange, F. Emily, A. Celine, K. Penelope, C. Anne-Sophie, D. M. Rolando, P. Michael, D. D. Correa, W. Shi, L. Abrey, L. DeAngelis, H. Thaler, E. J. Habets, R. Walchenbach, A. Kloet, H. Zwinkels, M. Klein, C. J. Vecht, M. J. Taphoorn, N. Ambachtsheer, D. van Nieuwenhuizen, J. J. Heimans, J. C. Reijneveld, S. M. Peerdeman, C. Lagemaat, K. B. Peters, D. A. Reardon, J. J. Vredenburgh, A. Desjardins, H. S. Friedman, P. H. Driever, E. Koustenis, G. Henze, L. De Sonneville, S. M. Rueckriegel, K. Mok, D. Klein, R. Del Maestro, K. Petrecca, A. Olivier, B. D. Schanker, W. T. Curry, K. Edelstein, B. J. Spiegler, S. Fung, T. Panzarella, D. C. Hodgson, D. J. Mabbott, N. Laperriere, U. Tabori, E. Bouffet, and W. P. Mason

Subjects
Cancer Research, Oncology, Neurology (clinical)
Published
2010
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3. Ongoing Clinical Trials

Author

J. L. Clarke, M. M. Ennis, K. R. Lamborn, M. D. Prados, V. K. Puduvalli, M. Penas-Prado, M. R. Gilbert, M. D. Groves, K. R. Hess, V. A. Levin, J. de Groot, H. Colman, C. A. Conrad, M. E. Loghin, K. Hunter, W. K. Yung, C. Chen, D. Damek, A. Liu, L. E. Gaspar, A. Waziri, K. Lillehei, B. Kavanagh, J. L. Finlay, K. Haley, G. Dhall, S. Gardner, J. Allen, A. Cornelius, R. Olshefski, J. Garvin, K. Pradhan, M. Etzl, S. Goldman, M. Atlas, S. Thompson, A. Hirt, J. Hukin, M. Comito, S. Bertolone, J. Torkildson, M. Joyce, C. Moertel, J. Letterio, G. Kennedy, A. Walter, L. Ji, R. Sposto, K. Dorris, L. Wagner, T. Hummel, R. Drissi, L. Miles, J. Leach, L. Chow, R. Turner, M. N. Gragert, D. Pruitt, M. Sutton, J. Breneman, K. Crone, M. Fouladi, B. B. Friday, J. Buckner, S. K. Anderson, C. Giannini, J. Kugler, M. Mazurczac, P. Flynn, H. Gross, E. Pajon, K. Jaeckle, E. Galanis, M. A. Badruddoja, M. A. Pazzi, B. Stea, P. Lefferts, N. Contreras, M. Bishop, J. Seeger, R. Carmody, N. Rance, M. Marsella, K. Schroeder, A. Sanan, L. J. Swinnen, C. Rankin, E. J. Rushing, L. F. Hutchins, D. M. Damek, G. R. Barger, A. D. Norden, G. Lesser, S. N. Hammond, J. Drappatz, C. E. Fadul, T. T. Batchelor, E. C. Quant, R. Beroukhim, A. Ciampa, L. Doherty, D. LaFrankie, S. Ruland, C. Bochacki, P. Phan, E. Faroh, B. McNamara, K. David, M. R. Rosenfeld, P. Y. Wen, S. Phuphanich, D. Reardon, E. T. Wong, S. R. Plotkin, A. Mintz, J. J. Raizer, T. J. Kaley, K. H. Smith, M. C. Chamberlain, C. Graham, M. Mrugala, S. Johnston, T. N. Kreisl, P. Smith, F. Iwamoto, J. Sul, J. A. Butman, H. A. Fine, M. Westphal, O. Heese, M. Warmuth-Metz, T. Pietsch, U. Schlegel, J.-C. Tonn, J. Schramm, G. Schackert, A. Melms, H. M. Mehdorn, V. Seifert, K. Geletneky, D. Reuter, F. Bach, M. Khasraw, L. E. Abrey, A. B. Lassman, A. Hormigo, C. Nolan, I. T. Gavrilovic, I. K. Mellinghoff, A. S. Reiner, L. DeAngelis, A. M. Omuro, S. R. Burzynski, R. A. Weaver, T. J. Janicki, G. S. Burzynski, B. Szymkowski, S. S. Acelar, L. L. Mechtler, P. C. O'Connor, H.-A. Kroon, T. Vora, P. Kurkure, B. Arora, T. Gupta, V. Dhamankar, S. Banavali, A. Moiyadi, S. Epari, N. Merchant, R. Jalali, S. Moller, K. Grunnet, S. Hansen, H. Schultz, M. Holmberg, M. M. Sorensen, H. S. Poulsen, U. Lassen, D. A. Reardon, J. J. Vredenburgh, A. Desjardins, D. E. Janney, K. Peters, J. Sampson, S. Gururangan, H. S. Friedman, S. Jeyapalan, M. Constantinou, D. Evans, H. Elinzano, B. O'Connor, M. Y. Puthawala, M. Goldman, A. Oyelese, D. Cielo, T. Dipetrillo, H. Safran, M. Anan, M. Seyed Sadr, J. Alshami, C. Sabau, E. Seyed Sadr, V. Siu, M.-C. Guiot, A. Samani, R. Del Maestro, U. Bogdahn, G. Stockhammer, A. K. Mahapatra, N. K. Venkataramana, V. E. Oliushine, V. E. Parfenov, I. E. Poverennova, P. Hau, P. Jachimczak, H. Heinrichs, K.-H. Schlingensiepen, S. Shibui, T. Kayama, T. Wakabayashi, R. Nishikawa, M. de Groot, E. Aronica, C. J. Vecht, S. T. Toering, J. J. Heimans, J. C. Reijneveld, T. Batchelor, P. Mulholland, B. Neyns, L. B. Nabors, M. Campone, A. Wick, W. Mason, T. Mikkelsen, L. S. Ashby, J. F. DeGroot, H. R. Gattamaneni, L. M. Cher, M. A. Rosenthal, F. Payer, J. Xu, Q. Liu, M. van den Bent, B. Nabors, K. Fink, M. Chan, J. Trusheim, S. Raval, C. Hicking, J. Henslee-Downey, M. Picard, D. Schiff, S. Karimi, L. M. DeAngelis, C. P. Nolan, A. Omuro, I. Gavrilovic, A. Norden, B. W. Purow, F. S. Lieberman, S. Hariharan, J. G. Perez-Larraya, J. Honnorat, O. Chinot, I. Catry-Thomas, L. Taillandier, J. S. Guillamo, C. Campello, A. Monjour, M. L. Tanguy, J. Y. Delattre, D. N. Franz, D. A. Krueger, M. M. Care, K. Holland-Bouley, K. Agricola, C. Tudor, P. Mangeshkar, A. W. Byars, T. Sahmoud, M. Alonso-Basanta, R. A. Lustig, J. F. Dorsey, R. K. Lai, L. D. Recht, N. Paleologos, M. Groves, S. Meech, T. Davis, D. Pavlov, M. A. Marshall, M. Slot, S. M. Peerdeman, P. D. Beauchesne, G. Faure, G. Noel, T. Schmitt, C. Kerr, E. Jadaud, L. Martin, C. Carnin, K. B. Peters, J. E. Herndon, J. P. Kirkpatrick, L. Nayak, K. S. Panageas, and L. M. Deangelis

Subjects
Clinical trial, Cancer Research, medicine.medical_specialty, Oncology, business.industry, medicine, Alternative medicine, Medical encyclopedia, Neurology (clinical), Health information, Intensive care medicine, business
Published
2010
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4. Radiation Therapy

Author

A. Charkravarti, M. Wang, I. Robins, A. Guha, W. Curren, D. Brachman, C. Schultz, A. Choucair, M. Dolled-Filhart, J. Christiansen, M. Gustavson, A. Molinaro, P. Mischel, T. Lautenschlaeger, A. Dicker, M. Mehta, C. A. Phillips, S. Dhulibala, D. Hallahan, J. Jaboin, F. S. Cardinale, P. Dickey, I. Goodrich, J. Gorelick, R. Sinha, V. M. Dest, C. Chen, C. Olsen, W. Franklin, B. Kleinschmidt-DeMasters, B. D. Kavanagh, K. Lillehei, A. Waziri, D. Damek, L. E. Gaspar, M. C. Stauder, N. N. Laack, M. J. Link, B. E. Pollock, P. J. Schomberg, J. F. Fraser, S. C. Pannullo, J. Moliterno, W. Cobb, P. E. Stieg, S. Vinchon-Petit, D. Jarnet, S. Michalak, A. Lewis, J.-P. Benoit, P. Menei, G. Desmarais, B. Paquette, R. Bujold, D. Mathieu, D. Fortin, K. C. Cuneo, J. J. Vredenburgh, J. H. Sampson, D. A. Reardon, A. Desjardins, K. L. Peters, J. P. Kirkpatrick, P. N. Patel, R. Vyas, U. Suryanarayan, D. Bhavsar, C. Hayhurst, E. Monsalves, M. Van Prooijen, C. Menard, G. Zadeh, C. Chung, K. Burrell, P. Lindsey, S. H. Burri, A. L. Asher, R. B. Kelly, P. Boltes, R. W. Fraser, F. A. Dilmanian, A. Rusek, N. R. Desnoyers, J. Y. Park, B. Dane, I. Dioszegi, S. D. Hurley, M. K. O'Banion, D. Tomasi, R. Wang, A. G. Meek, L. Sleire, J. Wang, J. Heggdal, P.-H. Pedersen, P. O. Enger, D. A. Clump, R. Srinivas, R. E. Wegner, D. E. Heron, S. A. Burton, A. H. Mintz, S. P. Howard, H. I. Robins, W. A. Tome, A. J. Paravati, P. A. Gardner, C. Snyderman, C. Ozhasoglu, A. Quinn, K. Seelman, J. H. Chang, Y. G. Park, M. J. Mehta, R. K. Vyas, D. C. Bhavsar, J. N. Guarnaschelli, L. Imwalle, J. Ying, C. McPherson, R. Warnick, J. Breneman, S. S. Khwaja, N. M. Wetjen, P. D. Brown, M. Siedow, U. Nestler, J. Perry, A. Huebner, A. Chakravarti, J. Glass, D. Andrews, M. Werner-Wasik, J. Evans, R. Lawrence, N. Martinez, G. Anuradha, M. David, M. Sara, L. Mark, B. Ricardo, J. Jeff, H. Juan, D. Kozono, P. Zinn, K. Ng, E. Melian, V. Prabhu, A. Sethi, K. Barton, D. Anderson, R. C. Rockne, M. Mrugala, J. Rockhill, and K. R. Swanson

Subjects
Cancer Research, Oncology, Neurology (clinical)
Published
2010
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5. Quality of Life

Author

M. R. Lucas, T. S. Armstrong, A. Acquaye, D. Balachandran, A. Mahajan, D.-H. Kang, E. Vera-Bolanos, M. R. Gilbert, M. P. Lovely, M. Page, K. Mogensen, J. Arzbaecher, C. Amidei, K. Lupica, M. E. Maher, P. Sherwood, S. Kagan, E. M. Sizoo, H. R. W. Pasman, J. C. Reijneveld, J. J. Heimans, L. Deliens, M. J. Taphoorn, R. Sheth, B. T. Bagan, M. N. Baig, C. Karas, D. I. Jacobs, S. A. Grimm, A. Rademaker, L. Rice, J. P. Chandler, K. Muro, M. Marymount, I. B. Helenowski, L. I. Wagner, C. L. Bennett, J. J. Raizer, A. Evans, G. Dhall, J. Finlay, K. Wong, G. McComb, R. Soffietti, R. P. Mueller, U. Abacioglu, S. Villa, F. Fauchon, B. Baumert, L. Fariselli, G. Tridello, M. Kocher, A. Bottomley, C. Pendleton, H. Adams, G. I. Jallo, B. S. Carson, E. Ahn, A. Quinones-Hinojosa, A. A. Acquaye, B. N. Bekele, J. Chandler, V. Nestor, K. Fink, M. Nashed, M. Linskey, D. A. Bota, W. Hoeben, K. Hilverda, T. J. Postma, J. Buter, J. Lenting, E. H. Collette, M. Klein, D. van Nieuwenhuizen, L. Bosscher, E. Szymanska, S. M. Peerdeman, T. Erdmann, S. N. Lawrence Recht, T. Armstrong, I. Gning, C. Cleeland, T. R. Mendoza, N. Jouniaux-Delbez, J. Y. Delattre, S. T. du Montcel, N. Butowski, R. Parvataneni, A. Nicole, K. Lamborn, M. Polley, J. Clarke, S. Chang, M. Prados, A. Liepa, P. Shi, D. Thornton, C. A. Kahlenberg, C. E. Fadul, R. Scott, D. W. Roberts, V. Thadani, K. Bujarski, E. C. Lallana, B. C. Jobst, J. G. Walker, D. Schultz, K. Grisdale, M. D. Groves, K. B. Peters, D. A. Reardon, J. J. Vredenburgh, A. Desjardins, H. S. Friedman, D. H. Allen, B. Carlson, V. Neelon, K. Giovanello, J. Carlson, R. Raynor, R. Lall, S. Ha, M. Marymont, S. Grimm, J. Raizer, and S. T. Keir

Subjects
Wait and scan, Meningioma, Health related quality of life, Cancer Research, Pediatrics, medicine.medical_specialty, Oncology, business.industry, medicine, Neurology (clinical), business, medicine.disease
Published
2010
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6. CLIN-NEURO/MEDICAL ONCOLOGY

Author

F. Girardi, C. Braun, Dennis C. Shrieve, Wei Chen, D. Kita, M. F. Fanelli, David Schiff, Sunyoung Ahn, Elizabeth Vera-Bolanos, J. Carrasquillo, S. Singer, James G. Herman, C. Bosa, Julia Selfridge, V. Tohidi, B.-A. Millar, M. Benavides, M. I. D. L. Fuente, Phioanh L. Nghiemphu, Kristin R. Swanson, John P. Kirkpatrick, Jonathan P.S. Knisely, Jörg C. Tonn, Kenneth Aldape, J. C. Streeter, R. Ruda, Seung Hong Choi, R. Curry, J. Yu, Ryo Nishikawa, E. Garoufalis, A. H. Friedman, Kurt A. Jaeckle, W. Zhang, Maryam Fouladi, Y. Odia, Arthur P. Chou, S. Sahebjam, E. Pentsova, Luis Souhami, Y. Yuan, F. N. Santos, C. Mesia, H. Friedman, Jennifer Linn, J. E. Adair, Yong Hwy Kim, Athanasios P. Kyritsis, Zvi Ram, M. G. Muhonen, Tracy T. Batchelor, Alissa A. Thomas, Stuart A. Grossman, M. Nasseri, Pedro Pérez Segura, S. Lacey, S. D. Bell, Helen A. Shih, E. Bit-Ivan, Timothy A. Chan, H. Pentsova, H. Wilson, Fumiko Shimizu, M. Forbes, L. Randolph, S. Kim, Amit Bhatt, Sabina Eigenbrod, T. Seigal, P. Dall'Occa, F. McSherry, R. M. Green, Michael D. Prados, Camilo E. Fadul, A. Guevarra, J.-Y. Han, Guido Reifenberger, E. Franceschi, D. Sageser, Jennie Taylor, Kevin Petrecca, M. K. Nicholas, Teresa Ribalta, Morris D. Groves, J.-Y. Blay, B. C. Beard, C. F. La, A. A. da Costa, K. Murillo-Medina, W. Pfisterer, R. Chu, Nan Lin, M. Ermani, A. J. Neuwelt, Samuel T. Chao, T. Ranjan, W. Taki, Hendrik Janssen, R. Agati, A. Mahta, T. N. Kreisl, E. Perez, J. Fuster, B. D. Fu, David M. Peereboom, N. Gresa-Arribas, Georg Widhalm, M. D'Apuzzo, J. Steinbach, Tom Mikkelsen, Michael Platten, R. Poggi, Sandra Ictech, I. Craven, A. Raghunathan, John B. Fiveash, N. L. Jansen, Rupert Egensperger, B. Badie, S. Medrano, Chul-Kee Park, K. Wong, Tae Min Kim, M. Bartolotti, M. Alejandro, T. Rosser, H.-P. Kiem, Marie-Christine Guiot, S. Gonzalez, J. Ljubimova, T. Furuta, J. Herndon, J. Finlay, Vivian Tabar, M. Hadjivassiliou, Christine Marosi, D. Hammoud, K. Black, S. K. Anderson, F. Bach, Gregory N. Fuller, N. Kased, S. Shpigel, Gianluca Marucci, Michael A. Vogelbaum, S. Bluml, J. Joo, M. D. Groves, X. Ye, Adam L. Cohen, J. A. Butman, M. D. Prados, X. Perez-Martin, R. Sharma, G. Colon-Otero, Richard M. Green, Paul D. Brown, Cornelia Sax, Robert J. Weil, J. Connelly, S. Burri, M. R. Welch, Marc K. Rosenblum, Minesh P. Mehta, Shlomit Yust-Katz, J. Canellas, Ulrich Bogdahn, S. Liker, P. U. Kumthekar, F. Gilles, M. Brock, Aaron T. Wild, A. Guerrero-Maldonado, Janet M. Bruner, A. Balmanoukian, E. Kitzweger, B. Schuknecht, Ayman I. Omar, J. Sampson, R. F. Del Maestro, W. Hruby, Niklas Thon, S. Zhao, F. Aboul-Enein, L. M. Alderson, J. McClain, J. Rudnick, J. Dorr, Vinay K. Puduvalli, Sonia Partap, Y. Hayashi, A. Kessinger, N. A. Shonka, T. Minamoto, D. Z. Lee, L. G. Berriel, T. Xie, J. Shih, J. S. Bubalo, Oscar Lin, J. E. Herndon, Michael Glantz, A. Gupta, H. Sabit, H. Heinrichs, Hans A. Kretzschmar, A. Asher, T. M. Bhavsar, A. Coan, V. A. Levin, M. Landeros, A. K. Choucair, D. Garbossa, G. Stockhammer, Jian Campian, C. J. Vecht, C. Ausch, Linda M. Liau, H. I. Farhat, M. Richards, H. I. Robins, R. Chaudhary, Agnieszka Korfel, Marta Penas-Prado, A. Jensen, I. Lolli, Amar J. Gajjar, K. Papsdorf, L. DeAngelis, Kathryn Beal, L. Phishniak, J. Joyce, Arnab Chakravarti, J. J. Vredenburgh, C. Dealis, A. F. Campos-Gines, Peter Hau, J.-I. Hamada, R. A. Gilbert, T. J. Kaley, Eric T. Wong, Ian F. Pollack, T. Gajewski, A. C. Levy, L. R. Bressler, X. Chen, C. Bernadette, O. Etxaniz, N. Antony, Birgit Flechl, D. Levacic, Byung Se Choi, J. I. Stenner, F. Pinto, Sandra K. Johnston, M. M. Mrugala, David Roberge, M. Wang, P. J. Anderson, H. A. Fine, M. J. Glantz, Alfred Yung, L. Alderson, M. Chamberlain, R. Naor, Jaume Capellades, Se-Hoon Lee, D. G. Brackman, Nathalie Jansen, T. Synold, Terri S. Armstrong, J. Pichler, X.-T. Kong, T. Cloughesy, P. Frankel, R. Valdez-Vazquez, Mathias Kunz, J. Dalmau, A. Baldock, Stewart Goldman, K. Rizzo, M. Nakada, Christoph Meisner, Ryan Merrell, C. Bomprezzi, Tomokazu Aoki, M. R. Gilbert, Jason K. Rockhill, Benjamin Ellezam, C. Sebastian, O. Arrieta, N. Wu, M. Magistrello, T. Patel, Adelheid Wöhrer, M. Sabel, F. Bokstein, V. Gomez-Molinar, S. Yovino, A. Kheder, Gaspar Reynes, R. Packer, M. Ronellenfitsch, Sasan Karimi, David Piccioni, J. M. Stachnik, C. Sebesta, Ryan Shanley, L. T. Chinen, H.-S. Gwak, E. A. Woyshner, D. Reuter, S. Bekker, K. Hunter, B. Haghighi, G. Poepperl, M. C. Chamberlain, W. Massey, M. A. Hamza, R. Cavaliere, Sichen Li, Daniela A. Bota, S. Spiegl-Kreinecker, G. Tatzreiter, Sigmund Hsu, M. Westphal, T. Pietsch, P. D. Barnes, C. Arango, G. Cervantes-Sanchez, C. Grommes, W. Brick, Vera Graute, M. P. Gabay, L. Bertero, Friedrich W. Kreth, F. M. Iwamoto, D. T. Blumenthal, M. Matsutani, K. B. Peters, S. F. Shakur, E. Flanagan, H. T. Kim, M. Simon, Michael Ackerl, Nadia N. Laack, J. Portnow, R. Ruckser, T. F. Cloughesy, H. Wayne Slone, A. A. Erazo-Valle-Solis, Karin Dieckmann, J. Baerhing, R. Soffietti, N. Laperriere, M. J. Gil, R. Fisher, Thierry Muanza, Reema R. Mody, W. Kim, L. Droms, Fabio M. Iwamoto, J. Grimm, Robert B. Jenkins, M. R. Aizenberg, E. Lipp, M. J. Taphoorn, V. Garcia-Navarro, J. H. Suh, Peter Bartenstein, E. Bourekas, Brett Theeler, W. G. Watkin, R. M. Tyson, Mira Zurayk, D. Alexandru, N. Uchiyam, J. Gilreath, A. J. Ramiro, R. Rockne, R. Naruse, M. Krieger, A. Kloet, Petr Kavan, E. Jaffe, D. A. Reardon, Jochen Herms, A. Willson, H. Zwinkels, M. Faedi, A. Moreno-Aspitia, J. Vredenburgh, Herbert H. Engelhard, C. Bridge, Paul W. Sperduto, H. Yoo, P. Friedman, N. Letarte, Tetsuya Ueba, Lisa M. DeAngelis, C. Nolan, Michael Weller, H. Colman, Jürgen Lutz, H. Ian Robins, J. McGregor, Pankaj Jalan, Joseph Landolfi, M. Di Battista, Bogdana Suchorska, Manuela Caroli, G. Nikkhah, A. Leibetseder, K. Aboody, V. Liu, Albert Lai, Yoshiki Arakawa, Kazuhiko Nozaki, G. Dhall, Kenneth R. Hess, Oscar Gallego, A. Naomi, A. Pace, T. M. Nguyen, K. Kawakami, K. DeBraganca, A. A. Brandes, V. K. Puduvalli, Lakshmi Nayak, Charles A. Conrad, Laurie E. Gaspar, P. J. Flynn, S. Ruiz-Gonzalez, Carmen Balana, J. Lange, T. Kaley, Vijay Pandav, J. Herrada, Eugenia Verger, S. Honigschnabel, M. Chen, C. A. Bridge, Yu Jung Kim, Mary Jo T. Necesito-Reyes, Bettina Hentschel, Victor A. Levin, J. Hu, K. Hoang-Xuan, Chae-Yong Kim, W. Sherman, L. Armbruster, T. Yun, C. Carapella, E. L. Diamond, A. Mahapatra, Warren P. Mason, X. Luo, R. C. Rockne, S. G. Crasto, L. Bailey, K. Sanghee, Matthias Preusser, R. Mathew, Jaclyn Wu, D. White, Susumu Miyamoto, A. Omuro, A. Desjardins, P.H. Gutin, J. S. Lee, Andrew D. Trister, Maxwell Lewis Neal, W. Zaky, A. L. Sumrall, C. M. Sperduto, A. L. Baldock, S. Phuphanich, J. Sul, S. H. Shin, E. A. Neuwelt, Heinrich Elinzano, C. Huang, H. S. Friedman, Laura Guyman, Sean Grimm, C. Sanchez, H. Newton, G. Oberhauser, Chunyue Yin, Wolfgang Wick, Caterina Giannini, Veronica Chiang, C. LaFougere, P. Metellus, A. Krauthammer, M. Kinoshita, J. Sheehan, Miguel J. Gil, E. Trevisan, J. Raizer, Shin-Ichi Miyatake, A. Olch, Jin Wook Kim, John L. Villano, Patricia Sneed, Brian P. O'Neill, A. Sahgal, Il Han Kim, A. Brickhouse, K. Herath, C. Zoccoli, M. J. van den Bent, T. Tsukahara, M. Heaney, B. Hassanzadeh, J. Quan, David R. Macdonald, Percy Ivy, D. Liue, John H. Suh, K. Miyashita, T. J. Fraum, W. A. Yung, I. Melguizo-Gavilanes, Maciej M. Mrugala, Matthew J. Matasar, and P. Garciarena

Subjects
Cancer Research, medicine.medical_specialty, Abstracts, Oncology, business.industry, medicine, Medical physics, Neurology (clinical), business
Published
2012

7. CLIN-SYMPTOM MANAGEMENT/QUALITY OF LIFE

Author

E. J. Habets, M. J. Taphoorn, S. Nederend, M. Klein, D. Delgadillo, K. Hoang-Xuan, A. Bottomley, A. Allgeier, T. Seute, A. M. Gijtenbeek, J. De Gans, R. H. Enting, C. C. Tijssen, M. J. Van den Bent, J. C. Reijneveld, H. Xu, K. Halbert, R. Bliss, J. Trusheim, M. A. Hunt, A. Bunevicius, S. Tamasauskas, A. Tamasauskas, V. Deltuva, K. M. Field, N. Guyatt, M. Fleet, M. A. Rosenthal, K. J. Drummond, H. Oliver, M. Tobias, V. Eva, S. Matthias, S. Johannes, S. Oliver, T. J. Christian, K. Dietmar, S. Gabriele, R. Thomas, G. Nikkhah, S. Uwe, L. Markus, W. Michael, W. Manfred, R. E. Strowd, K. Swett, M. Harmon, A. Pop-Vicas, M. Chan, S. B. Tatter, T. L. Ellis, M. Blevins, K. High, G. J. Lesser, A. Benouaich-Amiel, L. Taillandier, L. Vercueil, L. Valton, W. Szurhaj, A. Idbaih, J.-Y. Delattre, H. Loiseau, I. Klein, V. Block, C. Ramirez, F. Laigle-Donadey, E. Le Rhun, C. Harrison, A. Van Horn, C. Sapienza, C. Schlimper, H. Schlag, F. Weber, A. A. Acquaye, M. R. Gilbert, T. S. Armstrong, E. Vera-Bolanos, T. Walbert, V.-B. Elizabeth, M. Gilbert, M. L. Affronti, S. Woodring, K. Allen, J. E. Herndon, F. McSherry, K. B. Peters, H. S. Friedman, A. Desjardins, W. Freeman, S. Cheshire, C. Cone, K. H. Kalinowski, J.-Y. Kim, H. H. Lay, V. Poillucci, C. Southerland, J. Tetterton, J. Kirkpatrick, J. J. Vredenburgh, K. Edelstein, L. Coate, W. P. Mason, N. C. Jewitt, C. Massey, G. M. Devins, L. Lin, H.-H. Chiang, J. E. Cahill, C. M. Amidei, M. Lovely, M. D. Page, K. Mogensen, J. Arzbaecher, K. Lupica, M. E. Maher, H. T. Duong, D. F. Kelly, I. Gning, J. S. Wefel, T. R. Mendoza, C. S. Cleeland, B. Guthikonda, J. D. Thakur, A. Banerjee, C. Shorter, A. Sonig, I. S. Khan, G. L. Gardner, A. Nanda, K. Reddy, L. Gaspar, B. Kavanagh, A. Waziri, C. Chen, F. Boele, W. Hoeben, K. Hilverda, J. Lenting, A.-L. Calis, E. Sizoo, E. Collette, J. Heimans, T. Postma, M. Taphoorn, and J. Reijneveld

Subjects
Cancer Research, medicine.medical_specialty, Abstracts, Quality of life (healthcare), Oncology, Symptom management, business.industry, Medicine, Neurology (clinical), business, Intensive care medicine
Published
2012

8. CT of the liver in patients with metastatic breast carcinoma treated by chemotherapy: findings simulating cirrhosis

Author

J. J. Vredenburgh, Kay Washington, Erik K. Paulson, S. T. Young, Mark E. Baker, and D J Gulliver

Subjects
Adult, Liver Cirrhosis, medicine.medical_specialty, Pathology, Cirrhosis, medicine.medical_treatment, Mammary gland, Breast Neoplasms, Metastasis, Diagnosis, Differential, Radiologic sign, Humans, Medicine, Radiology, Nuclear Medicine and imaging, Aged, Retrospective Studies, Chemotherapy, Hyperplasia, business.industry, Liver Neoplasms, General Medicine, Middle Aged, medicine.disease, medicine.anatomical_structure, Liver, Female, Radiology, Differential diagnosis, Tomography, X-Ray Computed, business, Breast carcinoma
Abstract

Although the hepatotoxic effects of systemic chemotherapy are well known, CT findings in the liver after systemic chemotherapy have received little attention in the literature. In some patients with breast carcinoma metastatic to the liver who have received chemotherapy, a morphologic pattern develops similar to that associated with cirrhosis. This pattern is characterized by a lobular hepatic contour, segmental volume loss, and enlargement of the caudate lobe. The purpose of this study was to describe the CT appearance of this pseudocirrhosis and to correlate it with pathologic findings.We reviewed 65 CT examinations of 22 patients with stage IV breast carcinoma with hepatic metastases, who were receiving systemic chemotherapy and for whom abdominal CT scans showed pseudocirrhosis. Nineteen of 22 patients had follow-up CT scans at intervals ranging from 1 to 15 months. Criteria for the diagnosis of pseudocirrhosis included a lobular hepatic contour, segmental volume loss, and enlargement of the caudate lobe. CT findings were correlated with pathologic findings in seven patients.In all patients, CT scans showed retraction of the capsular surface of the liver (15 diffuse, seven focal) with a lobular margin, a finding also seen in advanced cirrhosis. The retraction occurred at the site of subjacent metastases. Findings evolved over 1-3 months. Six of seven patients had pathologic findings suggestive of nodular regenerative hyperplasia. No patients had pathologic evidence of cirrhosis.In patients undergoing systemic chemotherapy for breast cancer metastatic to the liver, a pattern may develop that mimics the CT appearance of hepatic cirrhosis. Pathologic findings suggest nodular regenerative hyperplasia as a possible cause.

Published
1994
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9. MEDICAL AND NEURO-ONCOLOGY

Author

G. K. Prithviraj, S. R. Sommers, R. L. Jump, B. Halmos, L. B. Chambless, S. L. Parker, L. Hassam-Malani, M. J. McGirt, R. C. Thompson, K. Hunter, M. C. Chamberlain, E. M. Le, E. L. T. Lee, Z. S. Sadighi, M. L. Pearlman, J. M. Slopis, T. S. Vats, S. Khatua, N. C. DeVito, M. Yu, R. Chen, E. Pan, T. Cloughesy, J. Raizer, J. Drappatz, M. Gerena-Lewis, J. Rogerio, S. Yacoub, A. Desjardin, M. D. Groves, J. DeGroot, M. Loghin, C. A. Conrad, K. Hess, J. Ni, S. Ictech, W. A. Yung, A. B. Porter, A. C. Dueck, N. J. Karlin, J. Olson, J. Silber, A. S. Reiner, K. S. Panageas, F. M. Iwamoto, T. F. Cloughesy, K. D. Aldape, A. L. Rivera, A. F. Eichler, D. N. Louis, N. A. Paleologos, B. J. Fisher, L. S. Ashby, J. G. Cairncross, G. B. Roldan, P. Y. Wen, K. L. Ligon, D. Shiff, H. I. Robins, B. G. Rocque, W. P. Mason, S. A. Weaver, R. M. Green, F. G. Kamar, L. E. Abrey, L. M. DeAngelis, S. C. Jhanwar, M. K. Rosenblum, A. B. Lassman, D. Cachia, L. Alderson, R. Moser, T. Smith, S. Yunus, K. Saito, A. Mukasa, Y. Narita, Y. Tabei, N. Shinoura, S. Shibui, N. Saito, B. Flechl, M. Ackerl, C. Sax, K. Dieckmann, R. Crevenna, G. Widhalm, M. Preusser, C. Marosi, C. Ay, D. Dunkler, I. Pabinger, C. Zielinski, M. Belongia, S. Jogal, K.-H. Schlingensiepen, U. Bogdahn, G. Stockhammer, A. K. Mahapatra, N. K. Venkataramana, V. Oliushine, V. Parfenov, I. Poverennova, P. Hau, P. Jachimczak, H. Heinrichs, A. G. Mammoser, N. A. Shonka, J. F. de Groot, I. Shibahara, Y. Sonoda, T. Kumabe, R. Saito, M. Kanamori, Y. Yamashita, M. Watanabe, C. Ishioka, T. Tominaga, A. Silvani, P. Gaviani, E. Lamperti, A. Botturi, F. DiMeco, G. Broggi, L. Fariselli, C. L. Solero, A. Salmaggi, E. A. Woyshner, F. Shu, Y. S. Oh, S. Iganej, G. Singh, S. L. Vemuri, B. J. Theeler, B. Ellezam, M. R. Gilbert, T. Aoki, H. Kobayashi, S. Takano, R. Nishikawa, M. Nagane, Y. Muragaki, K. Sugiyama, J. Kuratsu, M. Matsutani, L. A. Langford, V. K. Puduvalli, D. Shen, Z.-p. Chen, J.-p. Zhang, D. Bedekar, S. Rand, J. Connelly, M. Malkin, E. Paulson, W. Mueller, K. Schmainda, O. Gallego, M. Benavides, P. P. Segura, C. Balana, M. Gil, A. Berrocal, G. Reynes, J. L. Garcia, P. Murata, S. Bague, M. J. Quintana, V. G. Vasishta, K. Kobayashi, M. Tanaka, K. Tsuchiya, Y. Shiokawa, A. A. Bavle, K. Ayyanar, M. P. Prado, K. R. Hess, V. Liu, J. de Groot, M. E. Loghin, H. Colman, V. A. Levin, W. K. Alfred Yung, J. R. Hackney, C. A. Palmer, J. M. Markert, J. Cure, K. O. Riley, H. Fathallah-Shaykh, L. B. Nabors, M. G. Saria, C. Corle, J. Hu, J. Rudnick, S. Phuphanich, M. M. Mrugala, L. K. Lee, B. D. Fu, D. A. Bota, R. Y. Kim, T. Brown, H. Feely, A. Hu, J. W. Lee, B. Carter, S. Kesari, X.-T. Kong, S. Sparagana, E. Belousova, S. Jozwiak, B. Korf, M. Frost, R. Kuperman, M. Kohrman, O. Witt, J. Wu, R. Flamini, A. Jansen, P. Curtalolo, E. Thiele, V. Whittemore, P. De Vries, J. Ford, G. Shah, H. Cauwel, P. Edrich, T. Sahmoud, D. Franz, M. Khasraw, C. Brown, D. M. Ashley, M. A. Rosenthal, X. Jiang, Y. g. Mou, Z. p. Chen, M. Oh, E. kim, J. Chang, T. A. Juratli, M. Kirsch, G. Schackert, D. Krex, M. Wang, R. Stupp, M. Hegi, K. A. Jaeckle, T. S. Armstrong, J. S. Wefel, M. Won, D. T. Blumenthal, A. Mahajan, C. J. Schultz, S. C. Erridge, P. D. Brown, A. Chakravarti, W. J. Curran, M. P. Mehta, K. F. Hofland, S. Hansen, M. Sorensen, H. Schultz, A. Muhic, S. Engelholm, A. Ask, C. Kristiansen, C. Thomsen, H. S. Poulsen, U. N. Lassen, O. Zalatimo, C. Weston, C. Zoccoli, M. Glantz, S. Rahmanuddin, M. S. Shiroishi, S. Y. Cen, J. Jones, T. Chen, P. Pagnini, J. Go, A. Lerner, J. Gomez, M. Law, Z. Ram, E. T. Wong, P. H. Gutin, M. S. Bobola, M. Alnoor, D. L. Silbergeld, R. C. Rostomily, J. R. Silber, N. Martha, S. Jacqueline, G. Thaddaus, P. Daniel, M. Hans, M. Armin, T. Eugen, S. Gunther, M. Hutterer, H.-M. Tseng, C. M. Zoccoli, A. Patel, K. Rizzo, J. M. Sheehan, A. L. Sumrall, J. J. Vredenburgh, A. Desjardins, D. A. Reardon, H. S. Friiedman, K. B. Peters, L. P. Taylor, M. Stewart, N. A. Blondin, J. M. Baehring, T. Foote, N. Laack, J. Call, M. G. Hamilton, S. Walling, M. Eliasziw, J. Easaw, N. V. Shirsat, R. Kundar, A. Gokhale, A. Goel, A. A. Moiyadi, J. Wang, E. Mutlu, A. Oyan, T. Yan, O. Tsinkalovsky, H. K. Jacobsen, K. M. Talasila, L. Sleire, K. Pettersen, H. Miletic, S. Andersen, S. Mitra, I. Weissman, X. Li, K.-H. Kalland, P. O. Enger, J. Sepulveda, C. Belda, R. Sitt, L. Phishniak, F. Bokstein, M. Philippe, C. Carole, M. d. P. Andre, B. Marylin, C. Olivier, O. L'Houcine, F.-B. Dominique, N.-M. Isabelle, F. Frederic, F. Stephane, D. Henry, M. A. Errico, L. J. Kunschner, R. Soffietti, E. Trevisan, R. Ruda, L. Bertero, C. Bosa, M. G. Fabrini, I. Lolli, R. Jalali, P. K. Julka, A. K. Anand, D. Bhavsar, N. Singhal, R. Naik, S. John, B. S. Mathew, I. Thaipisuttikul, J. Graber, M. Shirinian, A. M. Fontebasso, K. Jacob, N. Gerges, A. Montpetit, A. Nantel, S. Albrecht, N. Jabado, K. Shah, K. Di, M. Linskey, N. Thon, S. Eigenbrod, S. Kreth, J. Lutz, J.-C. Tonn, H. Kretzschmar, A. Peraud, F.-W. Kreth, A. D. Muggeri, J. P. Alderuccio, B. D. Diez, P. Jiang, Y. Chao, M. Gallagher, R. Kim, S. Pastorino, V. Fogal, J. D. Rudnick, C. Bresee, A. Rogatko, S. Sakowsky, M. Franco, S. Lim, A. Lopez, L. Yu, K. Ryback, V. Tsang, M. Lill, A. Steinberg, R. Sheth, S. Grimm, I. Helenowski, A. Rademaker, F. P. Nunes, V. Merker, D. Jennings, P. Caruso, A. Muzikansky, A. Stemmer-Rachamimov, S. Plotkin, A. C. Spalding, T. W. Vitaz, D. A. Sun, S. Parsons, M. R. Welch, A. Omuro, K. Beal, D. Correa, T. Chan, L. DeAngelis, I. Gavrilovic, C. Nolan, A. Hormigo, T. Kaley, I. Mellinghoff, C. Grommes, K. Panageas, A. Reiner, R. Barradas, L. Abrey, P. Gutin, S. Y. Lee, B. Slagle-Webb, M. J. Glantz, J. R. Connor, C. A. Schlimper, H. Schlag, G. Stoffels, F. Weber, D. A. Krueger, M. M. Care, K. Holland, K. Agricola, C. Tudor, A. Byars, D. N. Franz, L. Rice, J. Chandler, R. Levy, K. Muro, L. Nayak, A. D. Norden, T. J. Kaley, A. A. Thomas, C. E. Fadul, L. P. Meyer, E. C. Lallana, M. Gilbert, K. Aldape, J. De Groot, C. Conrad, V. Levin, M. Groves, P. Chris, V. Puduvalli, S. Nagpal, A. Feroze, L. Recht, H. G. Rangarajan, M. W. Kieran, R. M. Scott, S. M. Lew, S. Y. Firat, A. D. Segura, S. A. Jogal, P. U. Kumthekar, S. A. Grimm, M. Avram, J. Patel, V. Kaklamani, K. McCarthy, M. Cianfrocca, W. Gradishar, M. Mulcahy, J. Von Roenn, E. Galanis, S. K. Anderson, J. M. Lafky, T. J. Kaufmann, J. H. Uhm, C. Giannini, S. K. Kumar, D. W. Northfelt, P. J. Flynn, J. C. Buckner, A. I. Omar, D. Schiff, A. Delios, A. Jakubowski, I. Melguizo-Gavilanes, W. Qiao, X. Wang, N. Hashemi-Sadraei, H. Bawa, G. Rahmathulla, M. Patel, P. Elson, G. Stevens, D. Peereboom, M. Vogelbaum, R. Weil, G. Barnett, M. S. Ahluwalia, E. C. Alvord, R. C. Rockne, J. K. Rockhill, R. Rostomily, A. Lai, J. Wardlaw, A. M. Spence, K. R. Swanson, G. Zadeh, H. Alahmadi, J. Wilson, F. Gentili, J. J. Beumer, J. Wright, N. Takebe, R. Gaur, M. Werner-Wasik, A. J. Gupta, A. Campos-Gines, K. Le, C. Arango, M. Richards, M. Landeros, H. Juan, J. H. Chang, J. S. Kim, J. H. Cho, C. O. Seo, A. L. Baldock, R. Rockne, P. Canoll, D. Born, K. Yagle, D. Alexandru, D. Bota, M. E. Linskey, S. Nabeel, S. N. Raval, J. Rosenow, M. Bredel, P. Z. New, S. R. Plotkin, J. G. Supko, W. T. Curry, A. S. Chi, E. R. Gerstner, T. T. Batchelor, N. Hashemi, S. T. Chao, R. J. Weil, J. H. Suh, M. A. Vogelbaum, G. H. Stevens, G. H. Barnett, D. Corwin, C. Holdsworth, R. Stewart, K. Swanson, J. J. Graber, A. R. Anderson, S. Jeyapalan, M. Goldman, J. Boxerman, J. Donahue, H. Elinzano, D. Evans, B. O'Connor, M. Y. Puthawala, A. Oyelese, D. Cielo, M. Blitstein, M. Dargush, A. Santaniello, M. Constantinou, T. DiPetrillo, H. Safran, C. Halpin, F. G. Barker, E. A. Maher, S. Ganji, R. DeBerardinis, K. Hatanpaa, D. Rakheja, X.-L. Yang, T. Mashimo, J. Raisanen, C. Madden, B. Mickey, C. Malloy, R. Bachoo, C. Choi, T. Ranjan, N. Yono, S. J. Han, M. Sun, M. S. Berger, M. Aghi, N. Gupta, and A. T. Parsa

Subjects
Cancer Research, medicine.medical_specialty, Abstracts, Oncology, business.industry, Neuro oncology, medicine, Medical physics, Neurology (clinical), business
Published
2011

10. The significance of tumor contamination in the bone marrow from high-risk primary breast cancer patients treated with high-dose chemotherapy and hematopoietic support

Author

J J, Vredenburgh, O, Silva, G, Broadwater, D, Berry, K, DeSombre, C, Tyer, W P, Petros, W P, Peters, and R C, Bast

Subjects
Adult, Dose-Response Relationship, Drug, Hematopoietic Stem Cell Transplantation, Breast Neoplasms, Pilot Projects, Middle Aged, Prognosis, Disease-Free Survival, Bone Marrow, Risk Factors, Lymphatic Metastasis, Antineoplastic Combined Chemotherapy Protocols, Humans, Female
Abstract

We studied the incidence and significance of tumor cell contamination of the bone marrow or peripheral blood progenitor cells of patients who had high risk primary breast cancer involving 10 or more axillary lymph nodes and who received high dose cyclophosphamide, cisplatin, and carmustine with hematopoietic support as consolidation following standard dose adjuvant chemotherapy. The autologous hematopoietic cell products were evaluated in 85 eligible patients. Eighty-three samples were available from the time of bone marrow harvest, and peripheral blood progenitor cells were evaluated from 57 of the 65 patients who additionally received these products. The screening technique utilized a panel of four anti-breast cancer monoclonal antibodies and an immunohistochemical technique. Thirty (36%) of the 83 evaluable patients had tumor cell contamination of the bone marrow. Only 2 (4%) of the 57 patients had tumor cell contamination of the peripheral blood progenitor cells. Tumor cell contamination of the bone marrow was associated with shorter disease-free survival and overall survival. In addition, the higher the number of tumor cells identified, the shorter disease-free and overall survival. There was no relationship between the tumor cell contamination of the bone marrow and the site of relapse. The combination of the log of the number of tumor cells +1 and number of positive lymph nodes predicted both disease-free and overall survival. Tumor cell contamination of the bone marrow from the harvest is associated with shorter disease-free and overall survival for patients who were treated with standard dose chemotherapy followed by consolidation with high dose alkylating agents and hematopoietic support. It is unclear what role the contaminating tumor cells have in relapse, and they may just be a high-risk marker. A comparison with other prognostic factors and characteristics of the tumor may determine the significance of the tumor contamination of the bone marrow.

Published
1997

11. The pharmacologic effects of recombinant, human colony-stimulating factors and their modulation by theophylline

Author

W P, Petros, G L, Rosner, J, Rabinowitz, C J, Gilbert, D, Coniglio, J J, Vredenburgh, M, Ross, and W P, Peters

Subjects
Adult, Metabolic Clearance Rate, Hematopoietic Stem Cell Transplantation, Granulocyte-Macrophage Colony-Stimulating Factor, Breast Neoplasms, Middle Aged, Aminophylline, Combined Modality Therapy, Recombinant Proteins, Area Under Curve, Antineoplastic Combined Chemotherapy Protocols, Granulocyte Colony-Stimulating Factor, Cytokines, Humans, Female, Prospective Studies, Half-Life
Abstract

To investigate the effect of colony-stimulating factors (CSFs) on drug metabolism using theophylline as a substrate (phase I), and to evaluate the influence of theophylline on endogenous serum cytokine concentrations (phase II).Open-label, prospective study.The bone marrow transplant unit of a tertiary university teaching hospital.Thirty-seven women with breast cancer (28 phase I, 9 phase II).Patients received aminophylline 0.58 mg/kg either as a 30-minute intravenous infusion before receiving recombinant CSFs or after several days of CSF therapy, just before high-dose chemotherapy (phase I) or as a continuous intravenous infusion after bone marrow transplantation (phase II).Clearance of theophylline was significantly higher after CSF administration (0.76 vs 0.99 ml/min/kg, p = 0.019). Continuous infusion of aminophylline resulted in elevations of serum macrophage-CSF and interleukin 6.Administration of CSFs before autologous bone marrow transplantation for priming progenitor cells may alter drug metabolism. Studies should be conducted to evaluate the potential effects of CSFs on the disposition of chemotherapeutic agents.

Published
1996

12. Ocular toxicity following high dose chemotherapy and autologous transplant

Author

P, Rubin, C, Hulette, J A, Khawly, M, Elkordy, A, Hussein, J J, Vredenburgh, G J, Jaffe, and W P, Peters

Subjects
Transplantation Conditioning, Paraneoplastic Syndromes, Hematopoietic Stem Cell Transplantation, Breast Neoplasms, Optic Nerve, Middle Aged, Combined Modality Therapy, Diagnosis, Differential, Fatal Outcome, Mastectomy, Modified Radical, Methotrexate, Doxorubicin, Ischemia, Antineoplastic Combined Chemotherapy Protocols, Humans, Female, Fluorouracil, Cisplatin, Visual Fields, Respiratory Insufficiency, Scotoma, Cyclophosphamide, Bone Marrow Transplantation, Demyelinating Diseases
Abstract

A 49-year-old woman received an autologous transplant for breast cancer. Six weeks later she noticed visual disturbance of the left eye which correlated with a visual field abnormality. There was a milder degree of visual disturbance in the right eye. Treatment with high-dose steroids partially stabilized the problem, which was felt to be an ischemic optic neuropathy. She ultimately died of respiratory failure. Pathology of the optic nerves revealed demyelination. Visual disturbances following high-dose chemotherapy are uncommon; the pathology to date has not been elucidated. Steroid therapy may be useful.

Published
1996

13. Thrombotic microangiopathy as a complication of high-dose chemotherapy for breast cancer

Author

D C, Fisher, G B, Sherrill, A, Hussein, P, Rubin, J J, Vredenburgh, M, Elkordy, M, Ross, W, Petros, and W P, Peters

Subjects
Lung Diseases, Anemia, Hemolytic, Time Factors, Platelet Count, Danazol, Hematopoietic Stem Cell Transplantation, Breast Neoplasms, Plasmapheresis, Combined Modality Therapy, Survival Analysis, Transplantation, Autologous, Risk Factors, Vincristine, Antineoplastic Combined Chemotherapy Protocols, Humans, Female, Blood Platelet Disorders, Retrospective Studies
Abstract

Five hundred and eighty-one patients with stage II-IV breast cancer were treated at Duke University Medical Center with high-dose chemotherapy, followed by hematopoietic support. All patients received a conditioning regimen of cyclophosphamide, cisplatin and carmustine. Of these patients, 15 (2.6%) developed symptoms similar to the hemolytic-uremic syndrome with evidence of thrombotic microangiopathy (TMA). The time of onset ranged from 75 days to 281 days post-transplant, with a median of 143 days. Hemolytic anemia and thrombocytopenia, without alternative cause, were required for diagnosis. All patients were treated with steroid therapy. In addition, 12 patients were treated primarily with plasmapheresis, and received a median of 46 treatments. Additional therapy included staphylococcal protein A column apheresis (eight patients), vincristine (three patients) and danazol (one patient). The mortality rate was 11 of 15 patients (73%). These patients had a median survival of 41 days from diagnosis of TMA (range 2-76 days). The four survivors are alive at 76, 186, 1837 and 2387 days from diagnosis of TMA. Three of these patients received twice daily plasmapheresis and protein A column apheresis therapy. One patient recovered without specific therapy. TMA is an infrequent complication of high-dose chemotherapy, but is associated with a high mortality. It frequently follows significant pulmonary drug toxicity. Survival may be improved with early diagnosis and aggressive plasmapheresis therapy.

Published
1996

14. Breast cancer cells are effectively purged from peripheral blood progenitor cells with an immunomagnetic technique

Author

C L, Tyer, J J, Vredenburgh, M, Heimer, W P, Peters, and R C, Bast

Subjects
Immunomagnetic Separation, Tumor Cells, Cultured, Antibodies, Monoclonal, Humans, Breast Neoplasms, Female, Hematopoietic Stem Cells
Abstract

Peripheral blood progenitor cells (PBPCs) are being used increasingly to provide hematopoietic support after intensive chemotherapy. However, many investigators have detected tumor cells contaminating PBPC collections. Methods that eliminate the tumor cells and spare the normal hematopoietic progenitor cells may improve the number of long-term, disease-free survivors after intensive chemotherapy. We developed an effective method using anti-breast cancer murine monoclonal antibodies (MoAbs) and immunomagnetic beads to eliminate a low percentage of breast cancer cells from PBPCs. We identified optimal anti-breast cancer MoAbs that react with membrane glycoproteins and conditions for selective removal of tumor cells. Using three anti-breast cancer MoAbs (260F9, 317G5, and 520C9) at 0.8 microgram/ml, a cell concentration of 2 x 10(8) cells/ml and a bead:total cell ratio of 0.75 beads:1 cell, we eliminated 3.3-4.8 (mean, 4.1) logs of tumor cells consistently from a model system with 1% breast cancer cells and 99% normal PBPCs. Similar levels of tumor cell elimination were obtained with three breast cancer cell lines. Colony-forming units were not affected adversely, with a mean recovery of 200% compared with the control. A clinical trial has begun that uses immunomagnetically purged, autologous bone marrow and PBPCs to support patients with metastatic breast cancer receiving high-dose chemotherapy.

Published
1996

15. Detection of tumor cells in the bone marrow of stage IV breast cancer patients receiving high-dose chemotherapy: the role of induction chemotherapy

Author

J J, Vredenburgh, W P, Peters, G, Rosner, K, DeSombre, W W, Johnston, A, Kamel, K, Wu, and R C, Bast

Subjects
Cohort Studies, Neoplasm, Residual, Bone Marrow, Antineoplastic Combined Chemotherapy Protocols, Humans, Breast Neoplasms, Female, Flow Cytometry, Combined Modality Therapy, Survival Analysis, Transplantation, Autologous, Bone Marrow Transplantation, Neoplasm Staging
Abstract

High-dose chemotherapy and hematopoietic support can produce long-term, disease-free remissions in selected patients with metastatic breast cancer. Occult bone marrow involvement may contribute to late relapse. We used five anti-breast cancer monoclonal antibodies and flow cytometry with cytological analysis of sorted immunostained cells to detect tumor cells in the bone marrow in two cohorts of patients. The first (Upfront) cohort was treated with a single course of high-dose chemotherapy and autologous bone marrow support (ABMS) without induction chemotherapy. The second (AFM) cohort received induction chemotherapy with doxorubicin, 5-fluorouracil and methotrexate prior to high-dose chemotherapy and ABMS. Of the 15 Upfront patients, seven (47%) had immunostained cells in the harvested bone marrow by flow cytometry and 8/15 (53%) had positive cytologies. Of the 49 AFM patients studied, nine (18%) had immunostained cells in the bone marrow, and only 1/49 (2%) had positive cytologies. Induction chemotherapy significantly decreased bone marrow contamination as detected by flow cytometry and cytology in patients with breast cancer. The detection of immunostained cells in the bone marrow did not predict for relapse or overall survival.

Published
1995

16. The impact of conventional plus high dose chemotherapy with autologous bone marrow transplantation on hematologic toxicity during subsequent local-regional radiotherapy for breast cancer

Author

L B, Marks, G L, Rosner, L R, Prosnitz, M, Ross, J J, Vredenburgh, and W P, Peters

Subjects
Adult, Aged, 80 and over, Platelet Count, Breast Neoplasms, Radiotherapy Dosage, Leukopenia, Adenocarcinoma, Middle Aged, Hematopoietic Stem Cells, Combined Modality Therapy, Thrombocytopenia, Transplantation, Autologous, Blood Cell Count, Leukocyte Count, Hematocrit, Chemotherapy, Adjuvant, Lymphatic Metastasis, Antineoplastic Combined Chemotherapy Protocols, Humans, Lymph Node Excision, Female, Mastectomy, Aged, Bone Marrow Transplantation
Abstract

Forty patients with Stage II-III breast cancer with 10 or more positive axillary nodes were treated with mastectomy followed by four cycles of standard dose CAF (cytoxan, Adriamycin, 5-FU), followed by high dose cytoxan, cisplatin, carmustine (HDCT) with autologous bone marrow transplant support (ABMT), and local-regional radiotherapy (LR XRT). During LR XRT, the hematologic toxicity experienced by these patients appeared more severe than that usually seen in patients not heavily pretreated with chemotherapy. Radiation therapy was interrupted in four patients (10%) because of thrombocytopenia and leukopenia. This observation prompted a comparison of the hematologic changes seen in this group with those seen in patients not treated previously with chemotherapy.A detailed analysis of changes in hematologic parameters during LR XRT was performed in 33 evaluable patients who received CAF-HDCT/ABMT and compared with a "control" group of 17 women who did not receive prior chemotherapy.The mean pretreatment leukocyte, platelet, and hematocrit counts were lower in the CAF-HDCT/ABMT group than in the control group, with the differences indicating statistical significance for the latter two (P = 0.17, P0.001, and P = 0.001, respectively). None of the control patients required a treatment interruption because of hematologic toxicity, whereas four of the CAF-HDCT/ABMT patients did. Among the CAF-HDCT/ABMT patients, a leukocyte count nadir of less than 2.0, a platelet nadir of less than 50,000, and a hematocrit nadir of less than 25 occurred in 12%, 19%, and 9%, respectively. The corresponding rates of control patients were 6%, 0%, and 0%, respectively. Relative to their pretreatment levels, however, both groups experienced similar declines in platelet and leukocyte counts.The higher rate of hematologic toxicity observed in the patients who previously received conventional chemotherapy plus HDCT/ABMT appears to have been due primarily to lower preradiotherapy blood counts.

Published
1994

17. The use of intensive clinic support to permit outpatient autologous bone marrow transplantation for breast cancer

Author

W P, Peters, M, Ross, J J, Vredenburgh, A, Hussein, P, Rubin, K, Dukelow, C, Cavanaugh, R, Beauvais, and S, Kasprzak

Subjects
Adult, Cost-Benefit Analysis, Hematopoietic Stem Cell Transplantation, Breast Neoplasms, Middle Aged, Combined Modality Therapy, Hospital Charges, Transplantation, Autologous, Antineoplastic Combined Chemotherapy Protocols, Ambulatory Care, Humans, Female, Bone Marrow Transplantation, Neoplasm Staging
Abstract

Recent studies have explored feasibility and cost considerations of administering high-dose chemotherapy with hematopoietic support in the outpatient setting. Between October 1991 and April 1993, we studied 110 women with primary metastatic breast cancer undergoing high-dose chemotherapy with hematopoietic support. Ninety-two patients were managed in an outpatient clinic after high-dose chemotherapy and autologous bone marrow transplantation and peripheral blood progenitor cells. The remaining 18 patients received the same high-dose treatment and hematopoietic support in the hospital and were discharged to a nearby hotel each night; these patients were the pilot group for this effort and also served as a control group. High-dose chemotherapy consisted of cyclophosphamide/cisplatin/carmustine. Chemotherapy was well tolerated, allowing 95% of 65 eligible patients enrolled since November 1992 to be discharged soon after chemotherapy for outpatient posttransplant support. Approximately 70% of these patients required either no hospital readmission or brief readmissions of 1 to 4 days. Median days of hospitalization required for historical groups of patients receiving high-dose chemotherapy plus bone marrow support as inpatient therapy, high-dose chemotherapy with colony-stimulating factor-primed peripheral blood progenitor cells and autologous bone marrow transplantation as inpatient therapy in a traditional transplant model, and outpatient management of autologous bone marrow transplantation patients were 37, 24.5, and 7 days, respectively, despite the same high-dose chemotherapy. Charges related to the transplant procedure were reduced by 50% over the last 2 to 5 years using the outpatient management approach. This procedure may be applicable to patients with other forms of cancer receiving intensive chemotherapeutic regimens. The use of outpatient management in a transplant setting is highly cost effective.

Published
1994

18. Clostridium septicum abscess in hepatic metastases: successful medical management

Author

M C, Thel, D, Ciaccia, J J, Vredenburgh, W, Peters, and G R, Corey

Subjects
Adult, Neutropenia, Liver Abscess, Breast Neoplasms, Ceftazidime, Immunocompromised Host, Sepsis, Antineoplastic Combined Chemotherapy Protocols, Granulocyte Colony-Stimulating Factor, Humans, Cyclophosphamide, Bone Marrow Transplantation, Etoposide, Clindamycin, Liver Neoplasms, Carmustine, Combined Modality Therapy, Imipenem, Methotrexate, Doxorubicin, Clostridium Infections, Drug Therapy, Combination, Female, Fluorouracil, Gases, Cisplatin
Abstract

Clostridium septicum bacteremia is frequently associated with hematologic and colonic malignancies and neutropenia. It frequently produces 'metastatic' gangrene with excessive mortality. Standard therapy usually includes surgical debridement and antibiotics. We present a patient with metastatic breast cancer treated with high-dose chemotherapy and bone marrow transplantation. She was treated successfully with antibiotics alone despite developing Cl. septicum bacteremia and gas in hepatic metastases. The pathophysiology of this infection is reviewed.

Published
1994

19. Post-mastectomy radiotherapy following adjuvant chemotherapy and autologous bone marrow transplantation for breast cancer patients with greater than or equal to 10 positive axillary lymph nodes. Cancer and Leukemia Group B

Author

L B, Marks, E C, Halperin, L R, Prosnitz, M, Ross, J J, Vredenburgh, G L, Rosner, and W, Peters

Subjects
Adult, Breast Neoplasms, Adenocarcinoma, Middle Aged, Carmustine, Combined Modality Therapy, Transplantation, Autologous, Survival Rate, Chemotherapy, Adjuvant, Doxorubicin, Antineoplastic Combined Chemotherapy Protocols, Humans, Female, Fluorouracil, Cisplatin, Cyclophosphamide, Mastectomy, Bone Marrow Transplantation, Retrospective Studies
Abstract

Between 2/87 and 2/91, 49 women with operable breast cancer involving greater than or equal to 10 axillary nodes were treated following mastectomy, with four cycles of Cyclophosphamide, Adriamycin, 5FU, followed by high doses of Cyclophosphamide, Cisplatin, Carmustine (HDCT) with autologous bone marrow transplant support. Forty patients received local-regional radiotherapy (generally to the chest wall, internal mammary, supraclavicular, +/- axillary nodal areas; minimum 44-50 Gy, 1.8-2 Gy/fraction, +/- 10-15 Gy scar boost; standard radiation techniques). The first nine patients did not receive local-regional radiotherapy. Three developed a local-regional failure (6-12 months after HDCT); six are without evidence of disease. Local-regional radiotherapy (LR XRT) was delivered to the subsequent 40 patients following HDCT+autologous bone marrow transplant. Six received less than 44 Gy of the planned local-regional radiotherapy due to significant toxicity and one of these failed locally. Only one local failure was observed among the 34 patients who received greater than or equal to 44 Gy. Two additional patients developed distant metastases. None of these 40 patients have failed in the axilla despite the fact that the axilla was irradiated in only 18 cases. Overall, 36/40 (90%) of these patients are without evidence of disease 4-30 months following HDCT (approximately 10-36 months after mastectomy, median 22 months). Radiotherapy was interrupted or discontinued because of progressive dyspnea, thrombocytopenia, or neutropenia in nine patients. Further studies to determine the roles of local-regional radiotherapy and HDCT in the development of these toxicities are underway. These encouraging results suggest that HDCT + autologous bone marrow transplant+local-regional radiotherapy may improve the survival rate in these high risk patients. A national randomized study to test the efficacy of this HDCT regimen is currently underway (Cancer and Leukemia Group B#9082 and Southwest Oncology Group #9114).

Published
1992

20. Purging of small cell lung cancer cells from bone marrow using immunomagnetic beads and a flow-through device

Author

E D, Ball, F J, Powers, J J, Vredenburgh, C A, Heath, and A O, Converse

Subjects
Magnetics, Deoxyribonucleases, Lung Neoplasms, Heparin, Bone Marrow Purging, Cell Adhesion, Temperature, Antibodies, Monoclonal, Humans, Serum Albumin, Bovine, Carcinoma, Small Cell, Microspheres, Bone Marrow Transplantation
Abstract

Immunomagnetic beads can be used to remove subpopulations of cells from a mixed cell suspension in a flow-through system. One application of this process is the removal of tumor cells from bone marrow prior to its use in autologous bone marrow transplantation (ABMT). Based on preliminary data showing that three monoclonal antibodies (MoAb) (SCCL 175, HNK-1, and TFS-4) gave optimal separation in small-scale experiments, we have designed a large-scale separator suitable for clinical use. In our separator, the cell suspension flows through a 150 ml baffled transfer pack which is held over an array of permanent magnets. Direct (one MoAb only) and indirect (MoAb and anti-mouse antibody) methods of binding beads to cells were investigated as were the effects of temperature, bead to cell ratio, and medium additives on tumor cell removal and normal cell recovery. We determined the optimal separation conditions to be the indirect method of binding at 22 degrees C using a bead to tumor cell ratio of 25:1. Testing of the device on DMS-273 small cell lung cancer (SCCL) cells mixed with normal human bone marrow mononuclear cells resulted in a mean tumor cell removal of 3.64 logs (99.977%) with a concomitant mean normal granulocyte-monocyte colony forming unit (CFU-GM) recovery of 61.3%. These experiments form the basis to use the immunomagnetic beads to purify bone marrow from patients with SCCL for use in ABMT.

Published
1991

21. Reactivity of anti-CD15 monoclonal antibody PM-81 with breast cancer and elimination of breast cancer cells from human bone marrow by PM-81 and immunomagnetic beads

Author

J J, Vredenburgh, W, Simpson, V A, Memoli, and E D, Ball

Subjects
Magnetics, Antigens, Neoplasm, Antibodies, Monoclonal, Humans, Lewis X Antigen, Bone Marrow Cells, Breast Neoplasms, Cell Separation, Antigens, Differentiation, Bone Marrow Transplantation
Abstract

The CD15 carbohydrate antigen, lacto-N-fucopentaose III is expressed on a variety of human cancer cells including acute myeloid leukemia, small cell carcinoma of the lung, and colorectal carcinomas. We have found that cells from breast cancer cell lines and patient-derived tissue are strongly CD15 positive, as seen by binding to the PM-81 monoclonal antibody. In this report we show that monoclonal antibody PM-81 and immunomagnetic beads can remove breast cancer cells from bone marrow and thus be used as "purging" agents for autologous bone marrow transplantation. PM-81 and immunomagnetic beads removed up to 3 log of SK-BR-3 and MCF7 breast carcinoma cell line cells while minimally affecting normal hematopoietic progenitor cells. This technique may be useful for purging marrow for autologous bone marrow transplantation in breast cancer.

Published
1991

22. Elimination of small cell carcinoma of the lung from human bone marrow by monoclonal antibodies and immunomagnetic beads

Author

J J, Vredenburgh and E D, Ball

Subjects
Lung Neoplasms, Antibodies, Neoplasm, Antibodies, Monoclonal, Bone Marrow Cells, Cell Separation, In Vitro Techniques, Flow Cytometry, Hematopoietic Stem Cells, Hematopoiesis, Magnetics, Antigens, Neoplasm, Immunologic Techniques, Humans, Carcinoma, Small Cell
Abstract

The majority of patients with small cell carcinoma of the lung (SCCL) have bone marrow involvement detected by monoclonal antibodies (mAb). High dose chemotherapy followed by autologous bone marrow transplantation may improve treatment results for patients with SCCL, but the bone marrow may need to be purged of contaminating tumor cells. This study investigates the reactivity of a panel of mAb with two SCCL cell lines and normal bone marrow and the ability of the mAb and immunomagnetic beads to eliminate the SCCL cells from a mixture of 90% normal bone marrow cells and 10% SCCL cells. The mAb and immunomagnetic beads removed 4 to 5 log of SCCL cells in the model system. The immunomagnetic separation did not significantly adversely affect normal hematopoietic progenitor cells, as determined by bone marrow colony-forming units. The results suggest that the mAb and immunomagnetic beads could safely and effectively separate SCCL cells from the bone marrow for autologous bone marrow transplantation following high dose chemotherapy.

Published
1990

23. Autologous bone marrow transplantation for acute myeloid leukemia following in vitro treatment with neuraminidase and monoclonal antibodies

Author

E D, Ball, J J, Vredenburgh, L E, Mills, G G, Cornwell, L, Schwarz, A L, Howell, and K, Troy

Subjects
Male, Bone Marrow, Leukemia, Myeloid, Acute Disease, Antibodies, Monoclonal, Humans, Lewis X Antigen, Neuraminidase, Complement System Proteins, Middle Aged, Antigens, Differentiation, Transplantation, Autologous, Bone Marrow Transplantation
Abstract

Although monoclonal antibodies (MoAbs) to CD15, especially PM-81, react with leukemic blasts from the majority of patients with acute myeloid leukemia (AML), a small subset of patients have cells that are CD15 negative or dim. We determined previously that neuraminidase will increase the reactivity of PM-81 with AML blasts, as well as blasts from many patients with acute lymphoblastic leukemia (ALL). In this report, we describe the laboratory results and clinical course of the first patient with AML whose harvested bone marrow was treated with neuraminidase prior to MoAbs and complement treatment. Neuraminidase increased the percentage of the patient's leukemia cells that reacted with PM-81 from 18% to 90% and more than doubled the percentage of AML blasts that were lysed by PM-81 and complement. The patient suffered no acute toxicity, engrafted rapidly, and was transfusion independent by day 21 post-ABMT. This report demonstrates the probable safety and efficacy of pretreatment of bone marrow with neuraminidase, and increases the number of patients with AML or ALL who may benefit from ABMT using marrow purging with MoAb to CD15.

Published
1990

24. Phase II trial of Gliadel plus O6-benzylguanic (O6-BG) for patients with recurrent glioblastoma multiforme

Author

J. A. Quinn, J. J. Vredenburgh, J. N. Rich, D. A. Reardon, A. Desjardins, S. Gururangan, A. H. Friedman, J. H. Carter, S. Threatt, and H. S. Friedman

Subjects
Cancer Research, Oncology
Abstract

2036 Background: The major mechanism of resistance to alkylnitrosourea therapy involves the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) which removes chloroethylation or methylation damage from the O6- position of guanine. O6-BG is an AGT substrate that inhibits AGT by suicide inactivation. A previous phase III randomized, placebo- controlled trial has shown that Gliadel wafer (G) significantly prolongs 6-month survival (55.5% for G vs. 35.6% for placebo) and median survival (28 weeks for G vs. 20 weeks for placebo) in patients with recurrent glioblastoma multiforme (GBM) (Brem et al 1995). Despite the success of G in prolonging survival we may be able to improve on this success by depleting AGT. Methods: Thus, we have designed a phase 2 trial where we define the activity and the toxicity of G in combination with a 5-day infusion of O6-BG in patients with recurrent GBM. In a prior study the O6-BG dose found to be effective in depleting tumor AGT activity at 48 hours was an IV bolus of 120 mg/m2 over 1 hour followed by a continuous infusion of 30 mg/m2/d for 48 hours. In order to guarantee depletion of tumor AGT activity for at least 5 days after G placement, this O6-BG bolus was repeated on days 3 and 5 while continuing the infusion. Results: To date, 47 patients have been enrolled out of a planned accrual of 50 patients. The 6-month survival is 80% and the median survival is 47 weeks. The adverse events include the following: 3 episodes of grade 3 CSF leak (6%), 7 episodes of grade 3 wound infection at craniotomy site (15%), 6 episodes of hyponatremia (13%), 3 episodes of hydrocephalus (6%), 1 episode of hygroma (2%), 1 episode of infectious meningitis (2%), 1 episode of arachnoiditis (2%), 1 episode of grade 3 fever (2%). Conclusions: Thus far, this data demonstrates an increase in the efficacy of G when combined with O6-BG. Three additional patients will be enrolled for a total accrual of 50 patients. [Table: see text]

Published
2007
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25. Phase II trial of Gliadel plus O6-benzylguanine (O6-BG) for patients with recurrent glioblastoma multiforme

Author

J. A. Quinn, J. J. Vredenburgh, J. N. Rich, D. A. Reardon, A. Desjardins, S. Gururangan, A. H. Friedman, K. Lavin, S. Sathornsumetee, S. Threatt, and H. S. Friedman

Subjects
Oncology, Cancer Research, medicine.medical_specialty, business.industry, Internal medicine, Recurrent glioblastoma, DNA Repair Protein, medicine, business, Alkyltransferase, Surgery
Abstract

1568 Background. The major mechanism of resistance to alkylnitrosourea therapy involves the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) which removes chloroethylation or methylation damage from the O6-position of guanine. O6-BG is an AGT substrate that inhibits AGT by suicide inactivation. A previous phase III randomized, placebo-controlled trial has shown that Gliadel wafer significantly prolongs 6-month survival (55.5% for Gliadel vs. 35.6% for placebo) and median survival (28 weeks for Gliadel vs. 20 weeks for placebo) in patients with recurrent glioblastoma multiforme (GBM) (Brem et al 1995). Despite the success of Gliadel in prolonging survival we may be able to improve on this success by depleting AGT. Methods. Thus, we have designed a phase 2 trial where we define the activity and the toxicity of Gliadel in combination with a 5-day infusion of O6-BG in patients with recurrent GBM. In a prior study the O6-BG dose found to be effective in depleting tumor AGT activity at 48 hours was an IV bolus of 120 mg/m2 over 1 hour followed by a continuous infusion of 30 mg/m2/d for 48 hours. In order to guarantee depletion of tumor AGT activity for at least 5 days after Gliadel placement, this O6-BG bolus was repeated on days 3 and 5 while continuing the infusion. Results. To date, 24 patients have been enrolled out of a planned accrual of 50 patients. Seventeen of these patients received prior nitrosourea therapy. The 6-month survival is 68% and the median survival is 36 weeks. The adverse events include the following: 2 episodes of CSF leak (8%), 4 episodes of wound infection at craniotomy site (16%), 5 episodes of grade ≥ 3 seizures (21%) and 3 episodes of hyponatremia (12%). These adverse events were similar in frequency to those seen in patients receiving Gliadel in prior placebo-controlled Gliadel trials. Conclusions. Thus far, this data demonstrates an increase in the efficacy of Gliadel when combined with O6-BG. Twenty-six additional patients will be enrolled for a total accrual of 50 patients. [Table: see text]

Published
2006
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26. A family with Sertoli-Leydig cell tumour, multinodular goiter, and DICER1 mutation.

Author

Haley M, Bindal P, McAuliffe A, and Vredenburgh J

Subjects
Adult, Female, Humans, Mutation, Syndrome, DEAD-box RNA Helicases genetics, Goiter genetics, Ovarian Neoplasms genetics, Ribonuclease III genetics, Sertoli-Leydig Cell Tumor genetics
Abstract

Background: DICER1 syndrome is an autosomal dominant tumour predisposition syndrome associated with a wide variety of cancerous and noncancerous conditions, including ovarian sex cord-stromal tumours and thyroid conditions, including multinodular goiter. The most common ovarian sex cord-stromal tumour associated with DICER1 syndrome is Sertoli-Leydig cell tumour, with germline DICER1 mutations present in more than 50% of cases. We present a case in which a patient in her late 30s was diagnosed with a Sertoli-Leydig cell tumour in the background of a strong family history of multinodular goiter and Sertoli-Leydig cell tumour with a germline mutation in DICER1 ., Case Presentation: A 38-year-old woman with history of multinodular goiter was found to have stage iiic ovarian Sertoli-Leydig cell cancer after presenting with abdominal pain. She underwent multiple surgeries and chemotherapy. The patient developed rapid disease progression and died 7 months after diagnosis. Seven years earlier, a daughter had experienced the same disease and was found to have a germline DICER1 mutation. The mother had not undergone testing before her own diagnosis., Summary: The co-occurrence of Sertoli-Leydig cell tumour and multinodular goiter is highly suggestive of DICER1 syndrome. The recognition of DICER1 syndrome within a family is essential for increased awareness and potential early recognition of complications. Most conditions associated with DICER1 syndrome occur in childhood, and most of the current screening recommendations are specific for childhood and young adulthood. Cancer risks and findings for the adult population are not as well defined. Clinicians who encounter DICER1 syndrome should review recommendations for genetic testing and surveillance and enrol patients in the DICER1 registry., Competing Interests: CONFLICT OF INTEREST DISCLOSURES We have read and understood Current Oncology’s policy on disclosing conflicts of interest, and we declare that we have none.

Published
2019
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27. Phase 1 study of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) in breast cancer patients after autologous peripheral blood progenitor cell (PBPC) transplantation.

Author

Bolwell B, Vredenburgh J, Overmoyer B, Gilbert C, Chap L, Menchaca DM, Cruickshank S, and Glaspy J

Subjects
Adult, Breast Neoplasms complications, Breast Neoplasms drug therapy, Cohort Studies, Consumer Product Safety, Drug Evaluation, Female, Filgrastim, Graft Survival drug effects, Granulocyte Colony-Stimulating Factor administration & dosage, Granulocyte Colony-Stimulating Factor toxicity, Hematopoietic Stem Cell Mobilization, Hematopoietic Stem Cell Transplantation standards, Hemorrhage chemically induced, Humans, Middle Aged, Platelet Count, Polyethylene Glycols pharmacology, Polyethylene Glycols toxicity, Recombinant Proteins administration & dosage, Recombinant Proteins pharmacology, Recombinant Proteins toxicity, Surface-Active Agents administration & dosage, Surface-Active Agents pharmacology, Surface-Active Agents toxicity, Thrombocytopenia chemically induced, Thrombopoietin pharmacology, Thrombopoietin toxicity, Time Factors, Transplantation, Autologous, Vascular Diseases chemically induced, Breast Neoplasms therapy, Hematopoietic Stem Cell Transplantation methods, Polyethylene Glycols administration & dosage, Thrombopoietin administration & dosage
Abstract

Forty-seven patients with stage II, III, or IV breast cancer undergoing autologous peripheral blood progenitor cell (PBPC) transplantation were randomized to placebo (n = 13) or to one of five sequential dose cohorts of pegylated (PEG) recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) (1.0, 2.5, 5.0, 7.5, or 10.0 microg/kg/day) (n= 34). Blinded study drug was started on the day of transplantation and was continued until the platelet count was > or =100 x 109/l or a maximum of 21 days. PBPCs were mobilized with filgrastim (r-metHuG-CSF) and all patients received filgrastim starting on day +2 after transplantation. The nadir platelet count was not affected by treatment. The median time to platelet recovery was 11 and 12 days for the placebo and combined PEG-rHuMGDF groups, respectively. No trends in adverse events suggested dose- or treatment-related toxicity. Two patients withdrew from the study because of an adverse event (allergic reaction in the 7.5 microg/kg group) probably related to study drug, and veno-occlusive disease (VOD) (in the 5 microg/kg group) which was felt not to be related to study drug by the investigator. No patients developed neutralizing antibodies to MGDF. Day +21 and day +28 platelet counts were higher in the group receiving PEG-rHuMGDF (246 vs 148 x 109/l and 299 vs 145 x 109/l, respectively; both P < 0. 05). PEG-rHuMGDF up to 10 microg/kg/day was well tolerated. In this study, there was no effect of study drug on initial platelet engraftment at the doses studied. However, the efficacy of other doses is unknown.

Published
2000
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28. A predictive model for relapse in high-risk primary breast cancer patients treated with high-dose chemotherapy and autologous stem-cell transplant.

Author

Nieto Y, Cagnoni PJ, Shpall EJ, Xu X, Murphy J, Vredenburgh J, Chao NJ, Bearman SI, and Jones RB

Subjects
Adult, Aged, Breast Neoplasms drug therapy, Breast Neoplasms mortality, Breast Neoplasms pathology, Breast Neoplasms, Male drug therapy, Breast Neoplasms, Male pathology, Breast Neoplasms, Male therapy, Carmustine administration & dosage, Cisplatin administration & dosage, Clinical Trials as Topic, Combined Modality Therapy, Cyclophosphamide administration & dosage, Disease-Free Survival, Female, Humans, Male, Middle Aged, Multivariate Analysis, Neoplasm Staging, Probability, Prognosis, Recurrence, Retrospective Studies, Survival Analysis, Transplantation, Autologous, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms therapy, Hematopoietic Stem Cell Transplantation
Abstract

High-dose chemotherapy (HDCT) is currently under evaluation for high-risk primary breast cancer (HRPBC), defined by extensive axillary nodal involvement or inflammatory breast carcinoma. Phase II studies of HDCT for HRPBC show that 30-40% of patients eventually relapse. We retrospectively reviewed 176 patients enrolled in clinical trials of HDCT for HRPBC at the University of Colorado and analyzed 23 potential predictive variables for relapse. All of the patients received the same regimen, with cyclophosphamide, cisplatin, and BCNU. Nine patients who experienced a toxic death were excluded from this analysis. The resulting predictive model was subsequently tested in an independent patient set treated at Duke University with the same HDCT regimen. Nodal ratio (number of involved nodes:number of sampled nodes), tumor size, grade, stage, estrogen receptor, progesterone receptor, and clinical inflammatory breast carcinoma correlated with risk of relapse. Nodal ratio, tumor size, and the combined estrogen receptor/progesterone receptor status were independent predictors. A scoring system using those three variables determines the risk of relapse, with a sensitivity and specificity of 60 and 90%, respectively, and a positive and negative predictive value of 65 and 88%, respectively. The differences in relapse-free survival and overall survival between high- and low-score patients were highly significant (P<0.000001). This model was subsequently validated in the Duke patient set. This model can identify two subgroups of HRPBC patients with low (12%) and high (65%) risk for recurrence after HDCT. Future research that tests new therapies will focus on those patients with a high score.

Published
1999

29. High-dose therapy with autologous hematopoietic cell support as salvage treatment for patients with breast cancer who have relapsed after previous high-dose chemotherapy.

Author

Bearman S, Vredenburgh J, Cagnoni P, Shpall E, Nieto Y, Ross M, Peters W, and Jones R

Subjects
Adult, Breast Neoplasms drug therapy, Breast Neoplasms mortality, Breast Neoplasms pathology, Carboplatin administration & dosage, Carmustine administration & dosage, Cisplatin administration & dosage, Combined Modality Therapy, Cyclophosphamide administration & dosage, Disease-Free Survival, Female, Humans, Ifosfamide administration & dosage, Life Tables, Melphalan administration & dosage, Middle Aged, Neoplasm Metastasis, Paclitaxel administration & dosage, Salvage Therapy, Survival Analysis, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms therapy, Hematopoietic Stem Cell Transplantation
Abstract

Twenty-six patients with breast cancer who had relapsed after previously receiving high-dose chemotherapy and autologous hematopoietic cell support received a second course of high-dose cytoreductive therapy and autologous hematopoietic cell support as salvage therapy. Several different high-dose therapy regimens were employed for the second transplant, including a radiolabeled immunoconjugate. Two patients died of treatment-related complications. The remaining 24 patients relapsed a median of 126 (range 22-635) days after salvage transplant. All have since died. The median survival after salvage transplant was 362 (range 31-931) days. We conclude that second courses of high-dose therapy as salvage treatment are generally well-tolerated but their efficacy is modest. Alternative treatment strategies are needed for these patients.

Published
1999
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30. The addition of paclitaxel to continuous infusion 5-fluorouracil is an active regimen for metastatic breast cancer.

Author

Vredenburgh J, Fishman R, Coniglio D, Matters L, Elkordy M, Ross M, Hussein A, Rubin P, Gilbert C, Petros W, and Peters WP

Subjects
Adult, Breast Neoplasms pathology, Female, Fluorouracil administration & dosage, Humans, Middle Aged, Neoplasm Metastasis, Paclitaxel administration & dosage, Remission Induction, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms drug therapy
Abstract

Metastatic breast cancer is commonly thought to be incurable. Treatment advances have resulted in increased response rates, although such responses are often more palliative than curative. A regimen of continuous infusion 5-fluorouracil (5FU) or continuous infusion 5-fluorouracil with paclitaxel was studied in patients with metastatic breast cancer and measurable disease. The induction therapy preceded high-dose ifosfamide, carboplatin, and melphalan in a phase I-II trial. Eighty-seven patients were enrolled in the trial. Forty-five received continuous infusion 5-fluorouracil as induction and 42 received 5-fluorouracil and paclitaxel. The single-agent, continuous infusion 5-fluorouracil cohort had one complete response (2%) and eight partial responses (18%). The combination continuous infusion 5-fluorouracil and 3-hour paclitaxel regimen produced four complete responses (10%) and 17 partial responses (40%). The combination regimen of continuous infusion 5-fluorouracil with bolus paclitaxel was well tolerated and with a 50% response rate, is an active regimen for women with metastatic breast cancer.

Published
1998
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31. Treatment of severe veno-occlusive disease with defibrotide: compassionate use results in response without significant toxicity in a high-risk population.

Author

Richardson PG, Elias AD, Krishnan A, Wheeler C, Nath R, Hoppensteadt D, Kinchla NM, Neuberg D, Waller EK, Antin JH, Soiffer R, Vredenburgh J, Lill M, Woolfrey AE, Bearman SI, Iacobelli M, Fareed J, and Guinan EC

Subjects
Adolescent, Adult, Bilirubin blood, Child, Child, Preschool, Drug Evaluation, Feasibility Studies, Female, Fibrinolytic Agents adverse effects, Hemorrhage chemically induced, Heparin therapeutic use, Hepatic Veno-Occlusive Disease mortality, Humans, Male, Multiple Organ Failure prevention & control, Neoplasms mortality, Neoplasms therapy, Palliative Care, Polydeoxyribonucleotides adverse effects, Receptors, Purinergic P1 drug effects, Retrospective Studies, Risk, Thalassemia therapy, Tissue Plasminogen Activator therapeutic use, Treatment Outcome, Fibrinolytic Agents therapeutic use, Hematopoietic Stem Cell Transplantation adverse effects, Hepatic Veno-Occlusive Disease drug therapy, Polydeoxyribonucleotides therapeutic use
Abstract

Hepatic veno-occlusive disease (VOD) is the most common of the regimen-related toxicities accompanying stem cell transplantation (SCT). Despite aggressive therapies, including the combination of tissue plasminogen activator (t-PA) and heparin, severe VOD is almost uniformly fatal. Defibrotide (DF) is a polydeoxyribonucleotide with activity in several vascular disorders and, unlike t-PA and heparin, produces no systemic anticoagulant effects. Nineteen patients who developed severe VOD after SCT were treated with DF on a compassionate-use basis. Patients had clinically established VOD and met risk criteria predicting progression and fatality. At the initiation of DF, all 19 patients had evidence of multiorgan dysfunction; median bilirubin was 22.3 mg/dL, 12 patients had renal insufficiency (5 dialysis dependent), 14 required oxygen supplementation, and encephalopathy was present in 8 patients. Beginning a median of 6 days after diagnosis of VOD, DF was administered intravenously in doses ranging from 5 to 60 mg/kg/d for a planned minimum course of 14 days. In no case was DF discontinued for attributable toxicity. No severe hemorrhage related to DF administration was observed. Resolution of VOD (bilirubin <2 mg/dL with improvement in other symptoms and signs) was seen in 8 patients (42%). Six of 8 responders survived past day +100, contrasted with the 2% predicted survival reported in comparable patients. The observed response rate, survival to day +100, and absence of significant DF treatment-associated toxicity are compelling and warrant further evaluation., (Copyright 1998 by The American Society of Hematology.)

Published
1998

32. Pharmacokinetic interaction between ondansetron and cyclophosphamide during high-dose chemotherapy for breast cancer.

Author

Gilbert CJ, Petros WP, Vredenburgh J, Hussein A, Ross M, Rubin P, Fehdrau R, Cavanaugh C, Berry D, McKinstry C, and Peters WP

Subjects
Antiemetics therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms therapy, Carmustine administration & dosage, Cisplatin administration & dosage, Combined Modality Therapy, Cyclophosphamide administration & dosage, Dose-Response Relationship, Drug, Doxorubicin administration & dosage, Drug Interactions, Fluorouracil administration & dosage, Hematopoietic Stem Cell Transplantation, Humans, Methotrexate administration & dosage, Ondansetron therapeutic use, Prospective Studies, Transplantation Conditioning, Antiemetics pharmacokinetics, Antineoplastic Combined Chemotherapy Protocols pharmacokinetics, Breast Neoplasms drug therapy, Cyclophosphamide pharmacokinetics, Ondansetron pharmacokinetics
Abstract

Purpose: Both ondansetron and cyclophosphamide are thought to be metabolized by hepatic microsomal processes. The purpose of this study was to evaluate the potential pharmacokinetic interactions between ondansetron and high-dose alkylating agent chemotherapy., Methods: A total of 54 breast cancer patients receiving high-dose cyclophosphamide, cisplatin and carmustine were treated prospectively in four sequential cohorts. Cohorts I and II received continuous infusions of both ondansetron and prochlorperazine, and cohorts III and IV received a continuous infusion of ondansetron alone at the same doses. All patients received lorazepam every 4 h. A group of 75 matched historical controls had received a continuous infusion of prochlorperazine with lorazepam. Pharmacokinetic monitoring of each drug used in the high-dose chemotherapy regimen was conducted., Results: Median AUCs of cyclophosphamide in patients receiving ondansetron (73.6 mg/ml x min) were lower than those of the control patients (88.3 mg/ml x min, n = 75, P = 0.0004), but the median cisplatin AUC was approximately 10% higher and no difference in the disposition of carmustine was demonstrated. Patients treated with ondansetron displayed a higher frequency of headaches than the controls. The frequency of achieving complete emetic control was greater in the ondansetron + prochlorperazine groups compared to the ondansetron alone groups and was greater in both these groups than in the prochlorperazine alone group on the first day of therapy only., Conclusion: Ondansetron altered the systemic exposure to cyclophosphamide when these agents were administered concomitantly. Ondansetron did not substantially improve overall emetic control when used alone but may improve control in combination with prochlorperazine. Future randomized studies are needed to delineate the effect of ondansetron on the disposition of the active cyclophosphamide metabolites so that clinical implications can be addressed.

Published
1998
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33. The effects of hyperthermia in bone marrow purging of breast cancer.

Author

Ingram SS, Samulski T, Dodge R, Prosnitz LR, Peters P, and Vredenburgh J

Subjects
Bone Marrow Transplantation, Breast Neoplasms pathology, Cell Death, Evaluation Studies as Topic, Female, Hematopoietic Stem Cells pathology, Humans, In Vitro Techniques, Neoplastic Stem Cells pathology, Transplantation, Autologous, Tumor Cells, Cultured, Tumor Stem Cell Assay, Bone Marrow Purging methods, Breast Neoplasms surgery, Breast Neoplasms therapy, Hyperthermia, Induced methods
Abstract

The number of autologous bone marrow transplants done for solid tumours, particularly breast cancer, has risen steadily over the last ten years. The role of bone marrow or peripheral blood progenitor cell purging in transplantation is incompletely understood. Theoretically, the reinfusion of untreated bone marrow containing tumour cells might result in relapse in some patients treated with high-dose chemotherapy and hematopoietic support. Therefore, safe and effective purging techniques may increase long-term, disease-free survivorship. In this study, hyperthermia was evaluated for its ability to purge CAMA-1 breast cancer cells from normal human bone marrow. Between two and nine trials of a range of temperatures (42-45 degrees C) and durations of treatment (1-4 h) were performed. The effect of hyperthermia on normal bone marrow alone and in mixes with breast cancer cells was also evaluated. Hyperthermia (45 degrees C, 4 h) produced > 5 logs of CAMA-1 cell kill. Exposures of 45 degrees C for 2 h and 44 degrees C for 4 h resulted in approximately three logs of cell kill, corresponding to < 1% survival of clonogenic cells. Normal bone marrow was considerably more vulnerable to heat treatments, however, with approximately 1% of progenitors remaining clonogenic after exposure of 43 degrees C for 2 h and 44 degrees C for 1 h. Therefore, although hyperthermia is able to achieve adequate CAMA-1 breast cancer cell kill, it remains more toxic to normal bone marrow as a purging method. To make hyperthermia useful in purging systems, mechanisms to selectively alter thermal sensitivity must be pursued.

Published
1996
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34. Effects of granulocyte-macrophage colony stimulating factor produced in Chinese hamster ovary cells (regramostim), Escherichia coli (molgramostim) and yeast (sargramostim) on priming peripheral blood progenitor cells for use with autologous bone marrow after high-dose chemotherapy.

Author

Hussein AM, Ross M, Vredenburgh J, Meisenberg B, Hars V, Gilbert C, Petros WP, Coniglio D, Kurtzberg J, and Rubin P

Subjects
Animals, Breast Neoplasms drug therapy, CHO Cells, Combined Modality Therapy, Cricetinae, Drug Administration Schedule, Escherichia coli, Humans, Melanoma drug therapy, Recombinant Proteins administration & dosage, Saccharomyces cerevisiae, Transplantation, Autologous, Bone Marrow Transplantation methods, Breast Neoplasms therapy, Glycoproteins administration & dosage, Granulocyte-Macrophage Colony-Stimulating Factor administration & dosage, Melanoma therapy, Recombinant Proteins therapeutic use
Abstract

Peripheral blood progenitor cells (PBPCs) were collected without prior association with chemotherapy but after the administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) produced in Chinese hamster ovary cells (CHO-GM, regramostim), Escherichia coli (E. coli-GM, molgramostim), or yeast (Yeast-GM, sargramostim) and used in conjunction with autologous bone marrow after high-dose chemotherapy in 69 patients with breast cancer or melanoma. The mean peripheral white blood cell (WBC) counts increased by 2.2 to 2.7-fold after regramostim, 4.5 to 7.3-fold after molgramostim and 4.3-fold after sargramostim. All patients underwent three leukaphereses. The mean (+/- standard error) total nucleated pheresed cells per kg x 10(8) were 4.15 +/- 0.56, 15.10 +/- 1.77 and 7.24 +/- 1.00 for patients receiving regramostim, molgramostim or sargramostim respectively. The mean (+/- standard error) granulocyte-macrophage colony-forming units per kg x 10(4) mobilized into the PB were 8.75 +/- 3.63, 71.03 +/- 17.85, and 65.11 +/- 18.74 for patients receiving regramostim, molgramostim, or sargramostim respectively. The total mean (+/- standard error) CD34+ cells per kg x 10(7) collected by three leukaphereses were 3.28 +/- 1.62, 1.34 +/- 0.51 and 2.57 +/- 1.93, for patients receiving regramostim, molgramostim or sargramostim respectively. The use of either molgramostim- or sargramostim-primed PBPCs led to complete elimination of absolute leukopenia with a WBC count under 100/mm3 in 64% and 77% of patients treated, respectively. Patients receiving molgramostim-primed PBPCs required fewer red blood cells transfusions than patients receiving regramostim-primed PBPCs (p = 0.0062). Our data indicate that PBPCs collected without prior association with chemotherapy but after either molgramostim or sargramostim with autologous bone marrow support and GM-CSF shorten the hematopoietic recovery after myeloablative chemotherapy in patients with breast cancer or melanoma.

Published
1995
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35. A radiologic syndrome after high dose chemotherapy and autologous bone marrow transplantation, with clinical and pathologic features of systemic candidiasis.

Author

Mudad R, Vredenburgh J, Paulson EK, Ross M, Meisenberg B, Hussein A, and Peters WP

Subjects
Adult, Amphotericin B therapeutic use, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Bone Marrow Purging, Combined Modality Therapy, Female, Fluconazole therapeutic use, Fungemia microbiology, Granulocyte Colony-Stimulating Factor therapeutic use, Granulocyte-Macrophage Colony-Stimulating Factor therapeutic use, Humans, Kidney Diseases diagnostic imaging, Liver Diseases diagnostic imaging, Middle Aged, Neutropenia etiology, Retrospective Studies, Splenic Diseases diagnostic imaging, Syndrome, Tomography, X-Ray Computed, Transplantation, Autologous, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bone Marrow Transplantation adverse effects, Breast Neoplasms drug therapy, Breast Neoplasms surgery, Candidiasis diagnostic imaging, Kidney Diseases etiology, Kidney Diseases microbiology, Liver Diseases etiology, Liver Diseases microbiology, Splenic Diseases etiology, Splenic Diseases microbiology
Abstract

Background: The use of high dose chemotherapy in the treatment of solid tumors is associated with prolonged neutropenia and, consequently, in some patients, systemic candidiasis. The authors describe their experience with a clinicoradiologic syndrome developing after high dose chemotherapy was administered to patients with breast cancer., Methods: The authors evaluated the clinical and radiologic records of 12 patients in whom hepatic, splenic, or renal candidiasis developed., Results: Three patients had positive blood cultures for candida tropicalis. One of these patients and two others had fungal organisms identified with special stains of an organ aspirate. Most patients were asymptomatic, and most of them were treated successfully with antifungal agents, although untreated patients also recovered. There were no fatalities due to the candidiasis., Conclusions: A radiographic syndrome resembling hepatic, splenic, or renal candidiasis is described, which occurred after high dose chemotherapy was administered and autologous bone marrow transplantation was performed on patients with breast cancer. This syndrome has a favorable prognosis. Conclusions as to the more indolent nature of this syndrome cannot be made; however, this topic warrants further investigation.

Published
1994
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36. Sequential prophylactic oral and empiric once-daily parenteral antibiotics for neutropenia and fever after high-dose chemotherapy and autologous bone marrow support.

Author

Gilbert C, Meisenberg B, Vredenburgh J, Ross M, Hussein A, Perfect J, and Peters WP

Subjects
Administration, Oral, Adult, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bacterial Infections etiology, Bone Marrow Purging, Bone Marrow Transplantation adverse effects, Ciprofloxacin therapeutic use, Drug Administration Schedule, Drug Therapy, Combination administration & dosage, Drug Therapy, Combination adverse effects, Female, Fever etiology, Humans, Injections, Intravenous, Middle Aged, Neutropenia etiology, Rifampin therapeutic use, Stem Cell Transplantation, Tobramycin therapeutic use, Vancomycin therapeutic use, Bacterial Infections prevention & control, Breast Neoplasms therapy, Drug Therapy, Combination therapeutic use, Fever prevention & control, Neutropenia prevention & control
Abstract

Purpose: We studied the effectiveness of prophylactic oral ciprofloxacin and rifampin on fever prevention in patients undergoing autologous bone marrow transplantation (ABMT) for breast cancer. Furthermore, we evaluated the toxicity and efficacy of empiric once-daily vancomycin and tobramycin for febrile neutropenia., Patients and Methods: Ninety-nine assessable women received prophylactic ciprofloxacin and rifampin after high-dose chemotherapy (HDC) for advanced or high-risk primary breast cancer supported with either bone marrow and peripheral-blood progenitor cells (PBPCs) or bone marrow purged with chemotherapy and monoclonal antibodies. Neutropenic fever was treated with empiric once-daily vancomycin and tobramycin. Patients were compared with historic controls treated with the identical HDC and bone marrow support regimen., Results: In patients treated with bone marrow and PBPCs, the incidence of fever during neutropenia was reduced by ciprofloxacin and rifampin from 98% to 57%. Documented infections were reduced from 42% to 13% (P < .01) and bacteremia from 18% to 0% (P < .001). In purged bone marrow recipients, the overall infection rate decreased from 74% to 17% (P < .001), and bacteremia from 29% to 7%. (P = .02). No patient developed breakthrough bacteremia or sepsis syndrome while on study. Serum creatinine level greater than 1.8 g/dL was noted in 7% of controls and 10% of study patients. Increased ototoxicity was not encountered with the higher peak concentrations of vancomycin and tobramycin., Conclusion: The therapeutic strategy of ciprofloxacin and rifampin followed by once-daily vancomycin and tobramycin markedly reduced the incidence of infection and virtually eliminated bacteremia in both purged and nonpurged bone marrow recipients. Once-daily vancomycin and tobramycin was safe and effective and, because of the ease of use, facilitates outpatient management of ABMT patients.

Published
1994
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37. Role of cytokines in autologous bone marrow transplantation.

Author

Peters WP, Ross M, Vredenburgh J, Hussein A, Meisenberg B, Gilbert C, Petros WP, and Kurtzberg J

Subjects
Ambulatory Surgical Procedures, Clinical Trials as Topic, Combined Modality Therapy, Humans, Transplantation, Autologous, Bone Marrow Transplantation methods, Cytokines therapeutic use
Abstract

High-dose chemotherapy with autologous bone marrow support has been increasingly used in the treatment of malignant disease. The use of hematopoietic colony-stimulating factors (CSF), particularly when coupled with the use of CSF-primed peripheral blood progenitor cells, has enabled a substantial reduction in the duration of severe leukopenia and in the morbidity associated with bone marrow transplantation. Furthermore, their use has reduced resource utilization and hospital charges and has also permitted the performance of autologous bone marrow transplantation support largely on an outpatient basis.

Published
1993

38. Comparative effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) on priming peripheral blood progenitor cells for use with autologous bone marrow after high-dose chemotherapy.

Author

Peters WP, Rosner G, Ross M, Vredenburgh J, Meisenberg B, Gilbert C, and Kurtzberg J

Subjects
Adult, Bone Marrow drug effects, Combined Modality Therapy, Granulocyte Colony-Stimulating Factor administration & dosage, Granulocyte Colony-Stimulating Factor therapeutic use, Granulocyte-Macrophage Colony-Stimulating Factor administration & dosage, Granulocyte-Macrophage Colony-Stimulating Factor therapeutic use, Hematopoiesis drug effects, Hematopoietic Stem Cell Transplantation, Humans, Middle Aged, Transplantation, Autologous, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bone Marrow Transplantation, Granulocyte Colony-Stimulating Factor pharmacology, Granulocyte-Macrophage Colony-Stimulating Factor pharmacology, Hematopoietic Stem Cells drug effects
Abstract

Two hematopoietic colony-stimulating factors, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF), have been shown to accelerate leukocyte and neutrophil recovery after high-dose chemotherapy and autologous bone marrow (BM) support. Despite their use, a prolonged period of absolute leukopenia persists during which infections and other complications of transplantation occur. We collected large numbers of peripheral blood (PB) progenitors after CSF administration using either G-CSF or GM-CSF and tested their ability to affect hematopoietic reconstitution and resource utilization in patients undergoing high-dose chemotherapy and autologous BM support. Patients with breast cancer or melanoma undergoing high-dose chemotherapy and autologous BM support were studied in sequential nonrandomized trials. After identical high-dose chemotherapy, patients received either BM alone, with no CSF; BM with either G-CSF or GM-CSF; or BM with G-CSF or GM-CSF and G-CSF or GM-CSF primed peripheral blood progenitor cells (PBPC). Hematopoietic reconstitution, as well as resource utilization, was monitored in these patients. The use of CSF-primed PBPC led to a highly significant reduction in the duration of leukopenia with a white blood cell (WBC) count under 100 and 200 cells/mL, and neutrophil count under 100 and 200 cells/mL with both GM- and G-CSF primed PB progenitor cells, compared with the use of the CSF with BM or with historical controls using BM alone. In addition, the use of CSF-primed PBPC resulted in a significant reduction in median number of antibiotics used, days in the Bone Marrow Transplant Unit, and hospital resources used. Patients receiving G-CSF primed PBPC also experienced a reduction in the median number of days in the hospital, red blood cell (RBC) transfusions, platelet transfusions, days on antibiotics, and discounted hospital charges. Phenotypic analysis of the CSF-primed PBPC indicated the presence of cells bearing antigens associated with both early and late hematopoietic progenitor cells. The use of CSF-primed PBPC can significantly improve hematopoietic recovery after high-dose chemotherapy and autologous BM support. In addition, the use of G-CSF-primed PBPC was associated with a significant reduction in hospital resource utilization, and a reduction in hospital charges.

Published
1993

39. Recognition of alcoholism among patients with psychiatric problems in a family practice clinic.

Author

Ramsay A, Vredenburgh J, and Gallagher RM 3rd

Subjects
Adolescent, Adult, Aged, Alcoholism diagnosis, Female, Humans, Male, Medical Records, Middle Aged, Retrospective Studies, Rural Population, Vermont, Family Practice, Outpatient Clinics, Hospital, Psychoses, Alcoholic diagnosis
Abstract

The prevalence of psychiatric disorders associated with alcoholism is reported to be as high as 65 percent. A retrospective chart study was performed to determine whether physicians in a primary care center were adequately evaluating for alcoholism their patients with psychiatric problems. Thirty-five percent of the patients with psychiatric problems seen over a six-month period were not questioned about alcohol use. Younger patients and those with a nonspecific psychiatric diagnosis were questioned even less frequently. In a review of the charts for signs of alcohol abuse, 23 percent of the psychiatric patients had signs of possible alcoholism, and 6 percent were definite alcoholics. Since the presence of alcoholism may significantly alter the approach to therapy, primary care physicians should fully evaluate all patients for this problem, especially if they present with a psychiatric disorder.

Published
1983

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