Core B: Patient enrollment, specimen and data management, and biostatistics. This core supports Projects 1 and 2 in four ways. First, the core is responsible for enrolling patients and collecting clinical information that is needed for Projects 1 and 2. Patients are categorized according to the presence of graft- versus-host disease (GVHD) activity and immunosuppressive treatment. This information is obtained primarily by abstracting medical records from providers at the Seattle Cancer Care Alliance and from referring physicians. Second, the core is responsible for procuring blood samples from selected patients who have outcomes that are informative for the development of tolerance after hematopoietic cell transplantation (HCT). For example, samples are routinely obtained from patients when they leave Seattle at approximately 3 months after HCT and when they return for evaluation at 1 year after HCT. In addition, a concerted effort is made to collect blood samples before the onset of immunosuppressive treatment in patients who develop chronic GVHD. Blood samples are also collected from patients before and after infusion of donor lymphocytes for treatment of recurrent malignancy following HCT. In these patients, blood samples are also obtained before immunosuppressive medications are given to treat any GVHD that might occur after donor lymphocyte infusion. These samples are likely to be particularly informative, since donor lymphocyte infusions are used only in patients who have no GVHD after immunosuppressive medications have been withdrawn. In these patients, immune reactions can be monitored with no potential interference from the effects of immunosuppressive medications. Third, the core is responsible for processing blood samples, enumerating cells that express CDS, CD4, CDS, CD25, CD127 and HLA-DR, and freezing samples for future use in Projects 1 and 2. Fourth, the core provides support for data management and biostatistical analysis of results from Projects 1 and 2.

Public Health Relevance

Immune reactions of donor cells against the recipient can cause complications when blood or marrow transplantation is used to treat leukemia and other diseases. The biological mechanisms that control these harmful immune reactions are not well understood. This core strengthens the overall program by providing investigators in Projects 1 and 2 with the clinical information and blood specimens needed for research studies that will help to identify the mechanisms that control these harmful immune reactions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI033484-18
Application #
8508161
Study Section
Special Emphasis Panel (ZAI1-SV-I)
Project Start
Project End
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
18
Fiscal Year
2013
Total Cost
$224,944
Indirect Cost
$97,135
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
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Hansen, John A; Hanash, Samir M; Tabellini, Laura et al. (2013) A novel soluble form of Tim-3 associated with severe graft-versus-host disease. Biol Blood Marrow Transplant 19:1323-30
Warren, Edus H; Matsen 4th, Frederick A; Chou, Jeffrey (2013) High-throughput sequencing of B- and T-lymphocyte antigen receptors in hematology. Blood 122:19-22
Chien, Jason W; Zhang, Xinyi Cindy; Fan, Wenhong et al. (2012) Evaluation of published single nucleotide polymorphisms associated with acute GVHD. Blood 119:5311-9
Marcondes, A Mario; Li, Xiang; Tabellini, Laura et al. (2011) Inhibition of IL-32 activation by ?-1 antitrypsin suppresses alloreactivity and increases survival in an allogeneic murine marrow transplantation model. Blood 118:5031-9
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Chronic GVHD Consortium (2011) Rationale and design of the chronic GVHD cohort study: improving outcomes assessment in chronic GVHD. Biol Blood Marrow Transplant 17:1114-20
Abbasi, Nissa; Vadnais, Barbara; Knutson, Jennifer A et al. (2011) Pharmacogenetics of intravenous and oral busulfan in hematopoietic cell transplant recipients. J Clin Pharmacol 51:1429-38
Bhatia, Smita; Davies, Stella M; Scott Baker, K et al. (2011) NCI, NHLBI first international consensus conference on late effects after pediatric hematopoietic cell transplantation: etiology and pathogenesis of late effects after HCT performed in childhood--methodologic challenges. Biol Blood Marrow Transplant 17:1428-35

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