The Experimental Transplantation and Immunology Branch (ETIB) clinical transplantation program has as goals the cure of cancer through hematopoietic stem cell transplant therapies, conducting outstanding translational research, and providing the highest level of excellence in clinical care. To this end, the Clinical Core of ETIB was developed. The ETIB Clinical Core provides interactions, activities and support across the branch. It represents a collection of individuals each with particular expertise in clinical transplantation and clinical research. While the section functions as a coordinated effort, it is also designed for individual career development and professional advancement for members.
Specific aims i nclude developing a supportive infrastructure for the conduct of clinical transplantation trials, establishing consistent clinical policies and practices in the care of transplantation patients in order to achieve excellence in clinical care, and providing and promoting educational opportunities in hematopoietic stem cell transplantation. Dr. Claude Sportes heads the Immunotherapy Unit of the core. Current research activities center on cancer vaccines in the setting of immune reconstitution following dose intensive chemotherapy. He also has interests in modulation of immune reconstitution by cytokines;he headed the trial to introduce IL-7 into formal phase 1 evaluation. This study was designed and executed by Dr. Sportes as a phase I, inter-patient dose escalation study. It sought to characterize the immunobiologic effects of rhIL-7 therapy in humans and, in particular, its potential for immune rejuvenation of T cell sub-populations. Sixteen subjects with non-hematologic cancer refractory to standard therapy were enrolled (National Cancer Institute, protocol 03-C-0152). RhIL-7 was an effective and well tolerated T cell growth factor with immune rejuvenating properties that suggested it would be effective in augmenting immune reactivity in patients with impaired immunity due to physiologic (age), iatrogenic (chemotherapy/ transplantation) or pathologic (HIV) lymphodepletion. Dr. Juan Gea-Banacloche heads the Infectious Disease Unit of the core. Infections are second only to relapse of malignancy as a cause of death after allogeneic transplant. Excellence in the management of infectious diseases is thus of the utmost importance in establishing a successful transplant program. Over the past 8 years, Dr. Gea-Banacloche has provided constant clinical care of the infectious diseases complications of patients registered on the transplant protocols of ETIB. Dr. Gea-Banacloche has been the source of clinical standards for the management of blood and marrow transplants in the Clinical Center. He has been the main architect of an inter-institute collaboration (NCI-NIAID-NHLBI) that has resulted in the NIH Clinical Center Guidelines for Infection Management of Hematopoietic Stem Cell Transplant Recipients. As part of the collaboration between NCI and NIAID, Dr. Gea-Banacloche has been instrumental in creating a fellowship in """"""""Infectious Disease in Immunocompromised Hosts"""""""", which will allow candidates with a background in Infectious Diseases, Hematology-Oncology and other disciplines in-depth exposure to the unique patient populations seen at the NIH Clinical Center as well as introduction to clinical or translational research. Dr. Steven Pavletic, M.D., is head of the GVHD and Autoimmunity Unit. The focus of the autoimmunity program is to study disease mechanisms that separate self-destructive autoimmunity from potentially beneficial autoimmune effects relevant to the treatment of cancer. In January 2003, Dr. Pavletic established an ETIB inter-institute cGVHD program to include a multidisciplinary clinic which brings together clinicians and scientists from eight NIH institutes (NCI, NIAID, NHLBI, NIAMS, NEI, NIDDK, NICHD, NIDCR) and the Clinical Center. The cGVHD clinic serves as a foundation for providing better care of patients and to study cGVHD. The clinic involves clinical researchers of various specialties such as hematology-oncology, pediatric oncology, ophthalmology, dermatology, rheumatology, rehabilitation medicine, pain and palliative care, gynecology, pulmonology, dentistry, oral surgery and others. Multiple laboratories are involved in basic science investigations in protocols based in the clinic. Key objectives of this interdisciplinary clinic-based program include developing new and better chronic GVHD assessment tools to standardize disease measurements in clinical trials, studying chronic GVHD biology, and developing new treatments for chronic GVHD. Dr. Pavletic has also organized efforts in cGVHD at other levels: Local leadership with a joint annual NIH/John Hopkins scientific workshop on cGVHD (held in May 2003 and 2004), regional leadership with formation of the Mid-Atlantic cGVHD consortium comprised of bone marrow transplanters and community oncologists in the region, establishment of a cGVHD patient support group with the DC Leukemia Society Chapter, and national/international leadership with formation of a group to formulate NIH consensus criteria for clinical trials in cGVHD. In collaboration with the extramural office at NIAID and national and international colleagues, Dr. Pavletic initiated a series of three expert workshops to explore pilot studies of allogeneic HSCT in patients with severe autoimmune disease. These three workshops were held in March 2005 (Bethesda) Exploring the feasibility of allogeneic transplantation for autoimmune disease;October 2005 (Newport Beach) Determining the best patient populations and October 2006 (Bethesda) Determining best transplant regimens and disease-specific toxicity issues. These works have been extensively cited since then, forming a basis for invigorating and standardizing the field. Dr. Bishop and Dr. Hardy initiated a similar effort in the area of relapse post transplant. This has resulted in an increased interest in developing new approaches for overcoming this barrier to allogeneic hematopoietic stem cell transplantation, and emphasized the importance of maintaining a focus on this area within the field.
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