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Browsing by Author "Sarantopoulos, Stefanie"
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Item The Biology of Chronic Graft-versus-Host Disease: A Task Force Report from the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease(Elsevier, 2017-02) Cooke, Kenneth R.; Luznik, Leo; Sarantopoulos, Stefanie; Hakim, Frances T.; Jagasia, Madan; Fowler, Daniel H.; van den Brink, Marcel R. M.; Hansen, John A.; Parkman, Robertson; Miklos, David B.; Martin, Paul J.; Paczesny, Sophie; Vogelsang, Georgia; Pavletic, Steven; Ritz, Jerome; Schultz, Kirk R.; Blazar, Bruce R.; Department of Pediatrics, School of MedicineChronic graft-versus-host disease (GVHD) is the leading cause of late, nonrelapse mortality and disability in allogeneic hematopoietic cell transplantation recipients and a major obstacle to improving outcomes. The biology of chronic GVHD remains enigmatic, but understanding the underpinnings of the immunologic mechanisms responsible for the initiation and progression of disease is fundamental to developing effective prevention and treatment strategies. The goals of this task force review are as follows: • Summarize the current state of the science regarding pathogenic mechanisms of chronic GVHD and critical knowledge gaps. • Develop working hypotheses/overriding concepts for chronic GVHD development. • Define the usefulness of current preclinical models to test working hypotheses and ultimately discover and develop new therapeutic strategies. • Identify shortcomings of preclinical models, and define criteria for the creation of additional models to address these limitations. This document is intended as a review of our understanding of chronic GVHD biology and therapies resulting from preclinical studies, and as a platform for developing innovative clinical strategies to prevent and treat chronic GVHD.Item National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Immune Dysregulation and Pathobiology Working Group Report(Elsevier, 2017-06) Gea-Banacloche, Juan; Komanduri, Krishna; Carpenter, Paul; Paczesny, Sophie; Sarantopoulos, Stefanie; Young, Jo-Anne; El Kassar, Nahed; Le, Robert Q.; Schultz, Kirk; Griffith, Linda M.; Savani, Bipin; Wingard, John R.; Medicine, School of MedicineImmune reconstitution after hematopoietic stem cell transplantation (HCT) beyond 1 year is not completely understood. Many transplant recipients who are free of graft-versus-host disease (GVHD) and not receiving any immunosuppression more than 1 year after transplantation seem to be able to mount appropriate immune responses to common pathogens and respond adequately to immunizations. However, 2 large registry studies over the last 2 decades seem to indicate that infection is a significant cause of late mortality in some patients, even in the absence of concomitant GVHD. Research on this topic is particularly challenging for several reasons. First, there are not enough long-term follow-up clinics able to measure even basic immune parameters late after HCT. Second, the correlation between laboratory measurements of immune function and infections is not well known. Third, accurate documentation of infectious episodes is notoriously difficult. Finally, it is unclear what measures can be implemented to improve the immune response in a clinically relevant way. A combination of long-term multicenter prospective studies that collect detailed infectious data and store samples as well as a national or multinational registry of clinically significant infections (eg, vaccine-preventable severe infections, opportunistic infections) could begin to address our knowledge gaps. Obtaining samples for laboratory evaluation of the immune system should be both calendar and eventdriven. Attention to detail and standardization of practices regarding prophylaxis, diagnosis, and definitions of infections would be of paramount importance to obtain clean reliable data. Laboratory studies should specifically address the neogenesis, maturation, and exhaustion of the adaptive immune system and, in particular, how these are influenced by persistent alloreactivity, inflammation, and viral infection. Ideally, some of these long-term prospective studies would collect information on long-term changes in the gut microbiome and their influence on immunity. Regarding enhancement of immune function, prospective measurement of the response to vaccines late after HCT in a variety of clinical settings should be undertaken to better understand the benefits as well as the limitations of immunizations. The role of intravenous immunoglobulin is still not well defined, and studies to address it should be encouraged.