Volume 11, Issue 12 , Pages 943-944, December 2005
National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: Preface to the Series
Article Outline
“Miracles do not occur at random”—C.D. Bowen
Chronic graft-versus-host disease (GVHD) desperately needs fresh attention. Current criteria for diagnosis and staging were developed 25 years ago and were based on a small single-center patient series [1], and the current standard therapy evolved from the principles developed in 1980s [2]. As a result of changing practices in allogeneic hematopoietic cell transplantation (HCT) and improvement in survival after HCT, the number of patients with chronic GVHD is increasing [3]. At the same time, chronic GVHD receives little attention at national meetings, and there is no Food and Drug Administration (FDA)–approved medication for chronic GVHD. Clinical research seeking to better understand chronic GVHD lags behind other innovations in HCT.
One of the main barriers to clinical research in chronic GVHD is the absence of standardized criteria for diagnosis, staging, and response criteria in this disorder [4, 5]. Several efforts have been made to address this problem, including discussions at the Tandem BMT meetings, but no structure exists to sustain these efforts. The idea of a National Institutes of Health (NIH)–sponsored conference on chronic GVHD was advanced after a joint Johns Hopkins and National Cancer Institute (NCI) workshop that addressed this subject in early 2003. It was clear that the problem needed more effort than could be sustained by a single or small group of investigators. Likewise, it was clear that the effort had to be supported by the broadest possible transplant constituency to avoid the development of different sets of staging/response criteria that has previously impeded progress in some other areas of medicine.
The Chronic GVHD Consensus Project started as a joint initiative of the intramural and extramural programs of the NCI, National Heart, Lung and Blood Institute, National Institute of Allergy and Infectious Diseases, and NIH Director’s Office and was swiftly embraced by the Health Resources and Services Administration and the Department of Defense Naval Medical Research Center. The FDA was involved early, because a major long-term goal of the project was the development of new therapies for chronic GVHD. The first planning meeting was held in June 2004 at the NIH offices in Rockville, MD, and included approximately 30 participants representing the HCT community, related specialty consultants, and government agencies. Six working groups were charged with preparing the introductory list of questions for each topic: diagnosis and staging of chronic GVHD, histopathology, biomarkers, response criteria, supportive care, and design of clinical trials. From the beginning, these groups tried to include as many stakeholders as possible so that recommendations would truly represent consensus opinion.
The work started in July 2004 with frequent conference calls of the larger working groups, the steering committee, and the planning committee to prepare draft documents for the second planning meeting, which was held in November 2004. Approximately 100 participants attended this meeting to prepare documents for the subsequent consensus meeting. The first public discussion of key recommendations in these draft documents took place at the February 2005 Tandem meeting in Keystone, CO, and the ensuing spirited discourse reaffirmed the imperative of this initiative.
To ensure wide participation at the June 2005 Consensus Meeting, members of European Group for Blood and Marrow Transplantation, American Society for Blood and Marrow Transplantation, Center for International Blood and Marrow Transplant Research, industry representatives, NIH scientists, and patient representatives were invited to attend. The meeting motto “Chronic GVHD—The Next Frontier in Transplantation Research” encapsulated the mood and enthusiasm of the 250 participants. The meeting was organized as a series of panel discussions to present the working group reports and a series of lectures focusing on issues critical for future research directions in the field. A 60-day public comment period regarding the working group reports ended in August 2005.
In this issue of Biology of Blood and Marrow Transplantation, the first working group’s report, “Diagnosis and Staging,” is published. This article will be followed each month by others from the remaining 5 working groups. Although these articles represent current consensus opinion guided by available published evidence, the recommendations are provisional and will need to be tested and validated in future clinical trials.
A follow-up meeting to revisit the recommendations after clinical application is planned for 2008. We invite all investigators to send information about chronic GVHD studies, protocols, and other relevant experience and to provide suggestions for refinements. These contributions should help to create a robust agenda for the follow-up meeting. Your comments can be submitted via the American Society for Blood and Marrow Transplantation chronic GVHD guidelines Web site (http://www.asbmt.org/cGvHD_Guidelines). Interested investigators and sponsors seeking partnerships should also contact the NCI Technology Transfer Branch (Web site: http://ttb.nci.nih.gov; telephone: 301-496-0477).
What comes next? This project has sparked renewed interest in chronic GVHD research. The recommendations that have emerged from this initiative are being applied in several projects in the United States, Canada, Europe, and Latin America. The broad participation of scientists at all levels in this effort has engaged a whole new generation of investigators. If progress is to be made in treatment of chronic GVHD, young investigators must perceive the field as interesting, exciting, and challenging at a basic and clinical level. Despite its obvious value, enthusiasm is not sufficient to carry us forward. Substantial effort must be directed toward establishing new partnerships focused on development of therapies for treatment of chronic GVHD. In August 2005, the NIH conducted a survey among investigators to identify the most critical directions for future chronic GVHD research, and the suggestions have been received. Finally, the new chronic GVHD recommendations were discussed in a highly collaborative and scientific atmosphere at a recent FDA Oncology Coordinating Committee meeting in July 2005. At that meeting, Stephanie Lee finished her presentation by saying, “Tougher nuts have been cracked.” This is now certainly true. We hope that you will find the chronic GVHD articles in this issue and subsequent issues to be helpful in your work. Congratulations go to all participants who gave so generously of their time and effort and to all those who in their hearts share the excitement of curing life-threatening diseases with the use of allogeneic HCT. The rewards go exclusively to our patients.
References
- Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients . Am J Med . 1980;69:204–217
- Alternating-day cyclosporine and prednisone for treatment of high-risk chronic graft-v-host disease . Blood . 1988;72:555–561
- . Chronic graft-versus-host disease . Biol Blood Marrow Transplant . 2003;9:215–233
- . How I treat chronic graft-versus-host disease . Blood . 2001;97:1196–1201
- . Chronic graft-versus-host disease (where do we go from here?) . Bone Marrow Transplant . 2004;33:569–577
PII: S1083-8791(05)00677-4
doi:10.1016/j.bbmt.2005.10.001
© 2005 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
Volume 11, Issue 12 , Pages 943-944, December 2005
