Notice Number: NOT-HL-12-147
Release Date: August 29, 2012
Response Date: September 20, 2012
National Heart, Lung, and Blood Institute (NHLBI)
National Cancer Institute (NCI)
The National Heart, Lung, and Blood Institute (NHLBI) and the National Cancer Institute (NCI) are considering building a national resource to better understand the disease progression of myelodysplastic syndromes (MDS), and are seeking input relevant to this project from the communities. Responses received will be used for project planning and to enhance study design.
An estimated 20,000 or more new cases of MDS are diagnosed in the United States each year. The incidence of MDS dramatically increases with age. MDS is a heterogeneous collection of clonal blood disorders characterized by ineffective hematopoiesis leading to anemia, neutropenia, and thrombocytopenia. While most cases occur in older adults, chemotherapy and other toxin-induced MDS and MDS due to inherited disorders occur in younger persons as well. Those suffering with this syndrome are predisposed to iron overload from repeated transfusions, lethal infections, and life-threatening bleeding. Nearly 30% of patients with MDS develop chemotherapy-resistant acute myeloid leukemia. Mortality resulting from hemorrhage or infection from failure of normal hematopoiesis is high. Most therapies for MDS are suboptimal and not curative.
MDS is frequently asymptomatic, but clinically suspected in older patients with abnormal routine blood tests, recurrent infections, or excessive bleeding. Diagnosis requires evaluation of bone marrow for evidence of cells that are maturing abnormally and malignant cells. These findings, combined with peripheral cytopenia(s), abnormal bone marrow cytogenetics, and the degree of transfusion dependence, classify patients with MDS into risk groups and provide a general assessment of disease severity and possible prognosis. Biomarkers clinically useful for accurate diagnosis, prognosis, and prediction of a patient’s response to therapy are not available.
Currently the etiologies of MDS are not well defined. Distinct mutations and genetic modifications are thought to underlie the molecular basis of MDS, some of which may be independent predictors of poor survival. A comprehensive standardized longitudinal clinical dataset and a consistently-processed, well-annotated biospecimen collection could provide national resources that potentially can be used to: (1) identify genetic, epigenetic and biological factors associated with initiation and progression of MDS; (2) uncover fundamental information on the changes that occur in hematopoietic stem cells and bone marrow stroma during normal aging; (3) reveal clinically useful biomarkers, and; (4) identify potential targets for new interventions. These resources could facilitate the conduct of basic and translational research on the evolution of MDS over time, and improve the diagnosis and clinical management of affected individuals.
Several approaches are being considered in building a national resource to study MDS in adults. One envisioned approach is to target adults with hematological abnormalities, in particular ones that require a bone marrow aspirate in order to diagnose or eliminate MDS as the diagnosis. Aspirates could undergo centralized multi-reader histopathology review to help ensure consistent diagnosis. From these individuals, up to 2000 adults diagnosed with MDS and a smaller group of participants to serve as comparators could be enrolled. Both groups could be followed over time to determine the natural history of the disease. Academic and community sites that participate in the NCI’s Clinical Trials Network would be encouraged to participate in this study. Data would be collected using a secure, web-based data management system, and biospecimens processed centrally using validated procedures, stored in the program’s central biorepository, and linked to their phenotypic and clinical data. Clinical data, genomic data, and biospecimens collected from the participants would be part of a national resource that could then be used by the scientific community to address important scientific questions related to MDS in adults.
NHLBI and NCI request your input on some or all of the following items regarding the design of a potential MDS natural history cohort study:
1. Comment on the approach described above, including the design and feasibility, the most important scientific questions that this study should answer, and/or critical elements missing from the proposed study design.
2. The importance of the selection of subjects for the comparator group, as well as the importance of age, gender, geographic location, medical history, and exposure histories in enrolling these participants and creating optimal value to the resource.
3. In addition to the information being collected for diagnosis of MDS, we welcome feedback about the clinical information that should be collected from participants and how often should this information be collected.
4. Collection of patient reported outcomes (e.g., functionality, symptoms, or other).
5. Biospecimens collected from study participants would be processed centrally, stored in a central biorepository, and made available to the extramural research community as an NHLBI resource. Comments on this approach should include, but are not limited to:
a. The type of biospecimens (e.g., plasma, DNA, cells) collection from each participant for both immediate and future research questions. Frequency of biospecimen collection from each participant. The frequency of collection differ between those diagnosed with MDS and the comparators.
b. Assays and molecular testing performed as part of this study to expedite future research in MDS.
c. The type of cells or tissues collected from each participant to serve as controls for future research.
6. Recruitment strategies that could be used to optimize participation and reduce barriers to enrollment.
7. Please provide any additional information pertinent to the proposed project that we should consider.
Responses to this RFI are voluntary. Any personal identifiers (e.g., names, addresses, e-mail addresses, etc.) will be removed when responses are compiled. Only the de-identified comments will be used. Proprietary, classified, confidential, or sensitive information should not be included in your response. The United States government reserves the right to use any non-proprietary technical information in any resultant solicitation(s).
This RFI is for information and planning purposes only and should not be construed as a solicitation or as an obligation on the part of the United States government to provide support for any ideas identified in response to it. Please note that the United States government will not pay for the preparation of any information submitted or for its use of that information. Responses will be compiled and shared internally with staff from the NHLBI and the NCI, and with the National Heart, Lung, and Blood Advisory Council, with one or more subcommittees of the Council, and with scientific working groups convened by the NHLBI, as appropriate. In all cases where responses are shared, the names of the respondents will be withheld.
How to Submit a Response
Interested extramural investigators and other interested parties are invited to respond.
Responses to this RFI will be accepted until September 20, 2012. You will not receive individualized feedback on any suggestions. No basis for claims against the United States government shall arise as a result of a response to this request for information or from the United States government's use of such information.
All comments must be submitted via e-mail as text or as an attached electronic document. Microsoft Word documents are preferred. Please submit your response to the following address:
Please direct all inquiries to:
Nancy L. DiFronzo, Ph.D.
John W. Thomas, Ph.D.
Elizabeth Wagner, M.P.H.
Division of Blood Diseases and Resources
National Heart, Lung, and Blood Institute, NIH
6701 Rockledge Drive, MSC 7950
Bethesda, MD 20892-7950
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