The objectives of the workshop are to review the major medical, economic, and social problems in adults with sickle cell disease and develop long-term strategies to address their needs through collaborative efforts with other government agencies (e.g., HRSA) and with patient advocacy groups such as the Sickle Cell Disease Association of America, (SCDAA).
D. Dr. Swerdlow will convene an ad hoc committee to draft a statement on behalf of the Committee prior to the next meeting regarding ICD 9 codes for diagnoses of hemoglobinopathies as well as various sequelae of the main diseases. Dr. Lane will assist.
It was not possible to do this up to this point but Dr. Swerdlow will continue with these efforts. The committee requested that Dr. Swerdlow come to the next meeting and report on his progress and he agreed.
E. Three draft initiatives that had been discussed at the previous meeting were reviewed by the committee (Comparison of Membrane Active Drugs in Adults with Sickle Cell Disease; Clinical Effectiveness of Hydroxyurea in Hb SC Disease, and the Effects of Sickle Cell Disease on the Lung). The committee rated the Lung initiative as top priority, followed by membrane active drugs and Hb SC disease/hydroxyurea.
Dr. Bonds noted that the initiative on Sickle Cell Disease and the Lung received a favorable rating from the Board of Extramural Advisors as well as Council. Funding will determine if this initiative can be released in the coming fiscal year. The other two initiatives were felt by the committee to warrant further work. Dr. Marie Stuart will review these two initiatives with a critical eye and see whether there might be a way to merge the two SC initiatives.
A. Centers for Disease Control: Ms. Adams noted the many changes occurring in the methods of testing being used for neonatal screening. A laboratory has been established at the CDC to address issues in newborn screening quality assurance and quality control with new equipment and additional personnel time. She will continue to update the committee on the progress in the area of newborn screening with newer technologies.
B. Health Resources and Services Administration: Dr. Marie Mann also announced a new program in newborn screening with $4 million targeted towards sickle cell disease. This program will involve follow up and counseling following early testing. The Secretary’s Advisory Committee on Genetic Testing (SACGT) assessment of HHS efforts to advance the appropriate use of genetic tests was discussed. The Sickle Cell Disease Advisory Committee was concerned about the lack of quality assurance in the testing being done by such programs except as monitored at the state level.
It was moved, seconded and unanimously approved that the :
As part of the Federal effort in the area of genetic testing that The Sickle Cell Disease Advisory Committee would recommend 1) Quality Control laboratories be established and 2) at least one reference laboratory be established.
C. Veterans Administration: No report given.
D. Department of the Army: No report given.
Update on Program Activities
A. Comprehensive Sickle Cell Centers Renewal Progress: Applications were received September 25, 2001, and there was a strong response. The review has taken place and investigators have been notified of their overall program scores. The summary statements with the full review and rating of the sub-projects should be available within approximately 6 weeks. Funding decisions will be made following secondary review by the NHLBI Advisory Council September 5-6, 2002.
B. Strategic Plan for a Gene-Based Cure for Beta-Chain Hemoglobinopathies: As reported to this committee previously, extramural investigators have proposed a two-armed, 11 part Strategic Plan for Gene-Based Cures for Beta-Chain Hemoglobinopathies. One arm deals with various aspects of the study of the mechanistic basis of induction of endogenous fetal hemoglobin genes, and the other arm deals with the development of gene therapy as a therapeutic modality for sickle cell disease and Cooley’s anemia. To date, from this plan two RFAs have been published, and one of these has been subsequently funded. The RFA that has been funded is entitled Transactivation of Fetal Hemoglobin Genes for Treatment of Sickle Cell Disease and Cooley’s Anemia. The other RFA that has been released but not yet funded is entitled Mechanisms of Fetal Hemoglobin Gene Silencing for Treatment of Sickle Cell Disease and Cooley’s Anemia. It will be funded in April, 2003. Additional RFAs are under consideration by the Institute. A Program Announcement targeted to small businesses has also been approved for release and is under development. It is entitled Chemical Screens for New Inducers of Fetal Hemoglobin for Treatment of Sickle Cell Disease and Cooley’s Anemia.
C. Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG): This contract began in August, 2000 with the funding of 10 peripheral clinical sites and a medical coordinating center. The investigator group has spent the first two years of the contract finalizing the protocol and trial design.
D. MSH Patients’ Follow-up: This prospective epidemiologic cohort study of the subjects who were originally enrolled in the Multicenter Study of Hydroxyurea (MSH Trial) is now entering its 5th year. The investigator group has demonstrated decreased mortality in those subjects who were begun on hydroxyurea in 1992 and who have continued on the drug with good fetal hemoglobin response since that time. Long term efficacy has been demonstrated in terms of persistence of fetal hemoglobin response, total hemoglobin response, and decreased morbidity secondary to consequences of decreased sickling. However, this patient population continues to have a high mortality rate secondary to the severity of their sickle cell anemia at time of study entry (3 or more crises per year). The leading causes of death in this cohort are death in acute crisis and pulmonary hypertension/chronic sickle lung disease. For this latter reason pulmonary testing is being included in further follow up.
E. Parvovirus B19 Study: This prospective epidemiologic cohort study involves pediatric subjects with sickle cell syndromes enrolled at 7 of the 10 current NHLBI-funded Comprehensive Sickle Cell Centers. These subjects are being followed to ascertain the B19 parvovirus seroprevalance, the seroconversion rate from negative to positive after B19 exposure, and the association, if any, between seroconversion and acute adverse events such as aplastic bone marrow crises or acute chest syndrome. Approximately 1,000 patients have been enrolled to date, and approximately 30% of subjects are seropositive so far. This study is scheduled to end in October, 2003. Infection by B19 parvovirus (which targets erythroid precursor cells) can be life-threatening for patients with hemolytic anemia. The NHLBI is evaluating plans to follow this study with clinical trials of an anti-B19 vaccine initially developed by Dr. Neal Young in intramural NHLBI, and subsequently tested in Phase I-II clinical trials by Medimmune. Medimmune is no longer involved in the clinical development of this vaccine, so NHLBI is evaluating plans to identify a new vaccine producer, and to potentially support additional Phase II and Phase III clinical trials.
F. STOP II Trial: This investigator initiated randomized clinical trial is designed to answer the question of whether or not chronic transfusion therapy can be safely withdrawn from subjects after 30 months of blood transfusions and normal transcranial doppler (TCD) surveillance studies.
G. Hip Core Trial: This investigator initiated randomized clinical trial is designed to ascertain the possible utility of hip coring as a treatment for patients with avascular necrosis of the hip.
H. CSSCD Cohort Study: The repository DNA samples are beginning to run out of material for analysis. The Sickle Cell Disease Advisory Committee encourages NHLBI to consider ways by which the utility of this resource can be prolonged and establish a minimum amount below which no more samples will be withdrawn anticipating a yet to be developed expansion technology.
I. Workshops and Projects 2002/2003
Title: Adults with Sickle Cell Disease: Meeting Unmet Needs (Workshop)
Date: June 13-14, 2002
Place: Natcher Building, (45) Bethesda, Maryland
Title: SCDAA National Sickle Cell Conference
Date: September 17-22, 2002
Washington Hilton Hotel
There was concern on the part of the committee regarding the cost of housing for this latter meeting such that it might inhibit attendance by trainees and families. The SCDAA will evaluate the possibility of alternative housing for future meetings.
Dates of Next Meetings
November 4, 2002
June 2, 2003
Areas of Program Needs and Opportunities
A. The issues of behavioral and psychosocial research were identified in particular with hopes expressed that the workshop on unmet needs will develop a strategic plan in these areas.
B. Staff was asked to identify speakers for the next meeting who could address statistical approaches and issues of small N clinical trials in pain research and potential surrogate markers of eye and bone disease in patients with SC disease.
Summary List of Action Items
A. The Protocol Review/DSMB Committees of BABY HUG are requested to report to the Committee regarding development of the protocol, age of participants, and considerations of therapeutic endpoints and potential toxicities. This clinical trial is on hold pending completion of review by NHLBI.
B. Dr. Swerdlow would also convene an ad hoc committee to draft a statement on behalf of the Committee prior to the next meeting. Dr. Swerdlow noted that he would coordinate an outreach for the Committee to the AMA regarding the ICD 9 codes for SC disease and sickle beta thalassemia disorders, Dr. Lane will assist.
C. Dr. Marie Stuart will review the two SC initiatives with a critical eye and see whether there might be a way to merge the two SC initiatives.
D. NHLBI will consider ways by which the utility of the CSSCD DNA resource can be prolonged and establish a minimum amount below which no more samples will be withdrawn thus anticipating a yet to be developed expansion technology.
Paul Swerdlow, M.D.
Sickle Cell Disease Advisory Committee
Charles M. Peterson, M.D.
Sickle Cell Disease Advisory Committee
Last updated: October 28, 2007