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Contributors
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- By Waiel Almoustadi, Brian J. Anderson, David B. Auyong, Michael Avidan, Michael J. Avram, Roland J. Bainton, Jeffrey R. Balser, Juliana Barr, W. Scott Beattie, Manfred Blobner, T. Andrew Bowdle, Walter A. Boyle, Eugene B. Campbell, Laura F. Cavallone, Mario Cibelli, C. Michael Crowder, Ola Dale, M. Frances Davies, Mark Dershwitz, George Despotis, Clifford S. Deutschman, Brian S. Donahue, Marcel E. Durieux, Thomas J. Ebert, Talmage D. Egan, Helge Eilers, E. Wesley Ely, Charles W. Emala, Alex S. Evers, Heidrun Fink, Pierre Foëx, Stuart A. Forman, Helen F. Galley, Josephine M. Garcia-Ferrer, Robert W. Gereau, Tony Gin, David Glick, B. Joseph Guglielmo, Dhanesh K. Gupta, Howard B. Gutstein, Robert G. Hahn, Greg B. Hammer, Brian P. Head, Helen Higham, Laureen Hill, Kirk Hogan, Charles W. Hogue, Christopher G. Hughes, Eric Jacobsohn, Roger A. Johns, Dean R. Jones, Max Kelz, Evan D. Kharasch, Ellen W. King, W. Andrew Kofke, Tom C. Krejcie, Richard M. Langford, H. T. Lee, Isobel Lever, Jerrold H. Levy, J. Lance Lichtor, Larry Lindenbaum, Hung Pin Liu, Geoff Lockwood, Alex Macario, Conan MacDougall, M. B. MacIver, Aman Mahajan, Nándor Marczin, J. A. Jeevendra Martyn, George A. Mashour, Mervyn Maze, Thomas McDowell, Stuart McGrane, Berend Mets, Patrick Meybohm, Charles F. Minto, Jonathan Moss, Mohamed Naguib, Istvan Nagy, Nick Oliver, Paul S. Pagel, Pratik P. Pandharipande, Piyush Patel, Andrew J. Patterson, Robert A. Pearce, Ronald G. Pearl, Misha Perouansky, Kristof Racz, Chinniampalayam Rajamohan, Nilesh Randive, Imre Redai, Stephen Robinson, Richard W. Rosenquist, Carl E. Rosow, Uwe Rudolph, Francis V. Salinas, Robert D. Sanders, Sunita Sastry, Michael Schäfer, Jens Scholz, Thomas W. Schnider, Mark A. Schumacher, John W. Sear, Frédérique S. Servin, Jeffrey H. Silverstein, Tom De Smet, Martin Smith, Joe Henry Steinbach, Markus Steinfath, David F. Stowe, Gary R. Strichartz, Michel M. R. F. Struys, Isao Tsuneyoshi, Robert A. Veselis, Arthur Wallace, Robert P. Walt, David C. Warltier, Nigel R. Webster, Jeanine Wiener-Kronish, Troy Wildes, Paul Wischmeyer, Ling-Gang Wu, Stephen Yang
- Edited by Alex S. Evers, Washington University School of Medicine, St Louis, Mervyn Maze, University of California, San Francisco, Evan D. Kharasch, Washington University School of Medicine, St Louis
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- Book:
- Anesthetic Pharmacology
- Published online:
- 11 April 2011
- Print publication:
- 10 March 2011, pp viii-xiv
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14 - Evaluating Therapeutic Response in Chronic Graft versus Host Disease
- from PART II - CLINICAL MANAGEMENT
- Edited by Georgia B. Vogelsang, The Johns Hopkins University School of Medicine, Steven Z. Pavletic, National Cancer Institute, Bethesda, Maryland
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- Book:
- Chronic Graft Versus Host Disease
- Published online:
- 26 August 2009
- Print publication:
- 20 April 2009, pp 146-156
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Summary
INTRODUCTION
Importance of Chronic GVHD Response Criteria
Chronic graft versus host disease (GVHD) is one of the major barriers to successful outcomes in allogeneic hematopoietic stem cell transplantation (HSCT). Undoubtedly, one of the key problems has been the lack of well-designed prospective clinical trials that test agents in chronic GVHD. Accepted endpoints for chronic GVHD studies are overall survival or permanent discontinuation of immunosuppression. While these endpoints may work for a large phase III trial, they are not acceptable for early phase trials. Moreover, they are endpoints that require one to control for significant confounding variables, thus necessitating larger sample sizes typically only achievable in multisite studies. Patients, investigators, and clinicians need results from smaller early phase studies that may indicate the potential efficacy of a specific agent for treatment of chronic GVHD. Unfortunately, few such early phase trials have been conducted, and the relative absence of clinically meaningful short, intermediate, and longer-term endpoints that can be feasibly and reliably measured may deter investigators from pursuing such drug development trials (Table 14.1).
The imperative to define response criteria that are reliable, valid, and sensitive to clinically important therapeutic change is clear. Chronic GVHD problem is increasing because of the decrease in early transplant-related mortality, more frequent use of donor-lymphocyte infusions, peripheral blood stem cells, increasing age of transplant recipients, and use of more alternative donors.
33 - Pediatric Chronic Graft versus Host Disease
- from PART IV - SPECIAL CONSIDERATIONS IN CHRONIC GVHD
- Edited by Georgia B. Vogelsang, The Johns Hopkins University School of Medicine, Steven Z. Pavletic, National Cancer Institute, Bethesda, Maryland
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- Book:
- Chronic Graft Versus Host Disease
- Published online:
- 26 August 2009
- Print publication:
- 20 April 2009, pp 369-385
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Summary
INTRODUCTION
Allogeneic Transplantation in Pediatrics
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is curative for many pediatric diseases. Most children transplanted for cancer, severe combined immunodeficiency syndrome, aplastic anemia, sickle cell anemia, thalassemia, and certain metabolic disorders are expected to survive. This has led to an ever-increasing population of longterm survivors. Recent studies demonstrate the major impact that late effects have on the individual survivors and society as a whole.
Chronic Graft versus Host Disease
Chronic graft versus host disease (cGVHD) is the most significant nonrelapse cause of morbidity and mortality following stem cell transplantation (SCT) for malignancies. Although the rates of cGVHD are lower in children than adults, the incidence of cGVHD in children has increased in association with the use of peripheral blood and unrelated donors. The manifestations and mechanisms of cGVHD in children and adults appear similar, although the natural history and response to therapy are different. cGVHD and its current treatments have a spectrum of deleterious effects on normal growth and organ development in children. In addition, the impact of prolonged immunosuppression is of particular concern in childhood, a critical time of immunologic development in response to common infections and immunizations.
Data and research focused on cGVHD in pediatrics are limited. Most studies are small and are often grouped into larger adult series. In comparison to adults, relatively small numbers of children and adolescents undergo transplantation.