Chronic Graft-Versus-Host Disease in Patients Who Have Undergone Donor Stem Cell Transplant

Targeted Single Nucleotide Polymorphisms (SNPs) to Classify Subtypes of Chronic Graft-Versus-Host Disease (cGVHD) After Allogeneic Transplant.

RATIONALE: Studying samples of tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to chronic graft-versus-host disease in patients who have undergone donor stem cell transplant.

PURPOSE: This phase I trial is studying chronic graft-versus-host disease in patients who have undergone donor stem cell transplant.

OBJECTIVES:

• To determine and define the biological basis of different subtypes of chronic graft-vs-host disease using a targeted single nucleotide polymorphisms approach in patients who have undergone allogeneic stem cell transplantation.

OUTLINE: Two important aspects of the methodologies that will be employed for the analysis of SNPs associated with GVHD are throughput efficiency to be able to perform the assays on a reasonable number of samples as well as having the ability to add or remove SNPs to the assay panel. While a genome-wide association study to identify variants associated with GVHD would offer an unbiased approach, our patient cohort size would not allow significant statistical power in the study. Therefore, a more targeted approach using two established technologies is proposed.

The Sequenome assay uses the unique combination of a single-base primer extension assay incorporating one of four modified nucleotides. The four modified nucleotides each have a unique mass that allows them to be distinguished from one another using mass spectrometry. Each SNP is determined analyzing the primer extension product from a PCR amplicon that surrounds the SNP of interest. The development of each assay involves designing flanking PCR primers and an internal extension assay using web-based software provided by Sequenome. The assays can be designed to analyze up to 30 SNPs in a single reaction, providing a customizable, efficient and high-throughput assay for SNPs of interest.

DISEASE CHARACTERISTICS:

• Underwent prior matched related or unrelated allogeneic stem cell transplantation (SCT)

  • Presence OR absence of chronic graft-vs-host disease after day 100 and alive after day 180 post-transplantation

• No T-cell depleted SCT, cord blood transplantation, mismatched allogeneic transplantation, or autologous transplantation

• Available recipient and donor DNA (samples collected from the Vanderbilt University or the Fred Hutchinson Cancer Center tissue bank)

PATIENT CHARACTERISTICS:

• Not specified

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics