Improving Outcomes Assessment in Chronic GVHD

• Overall survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
• Time to discontinuation of immunosuppression [ Time Frame: 3 years ] [ Designated as safety issue: No ]
• Functional impairments [ Time Frame: 3 years ] [ Designated as safety issue: No ]

• Provider perception of change [ Time Frame: 6 months ] [ Designated as safety issue: No ]
• Patient perception of change [ Time Frame: 6 months ] [ Designated as safety issue: No ]
• Changes in immunosuppressive medications [ Time Frame: 6 months ] [ Designated as safety issue: No ]

The purpose of this study is to see if recent guidelines proposed by the National Institutes of Health for the diagnosis, staging, and response assessment of people with chronic GVHD can improve our understanding of this complication. We will accomplish our goals by studying a large number of people with chronic GVHD over several years using information collected from health care providers, patients, laboratory studies and diagnostic tests. Several transplant centers in the United States are collaborating on this project.

Chronic graft-versus-host disease (GVHD) is one of the most devastating long-term complications after infusion of allogeneic hematopoietic stem cells, and it remains one of the major barriers to successful transplantation. Relatively little progress has been made in understanding and improving treatments for chronic GVHD over the last 20 years, and the survival rate after diagnosis of chronic GVHD has barely improved despite advances in supportive care. The National Institutes of Health convened a Consensus Conference on this topic in June 2004 and recently published its recommendations on improving research methods in a series of six papers.

In our study, we will establish a multi-center, observational, longitudinal cohort in order to improve outcomes assessment in chronic GVHD with the specific aims of (1) validating prognostic factors for risk stratification; and (2) defining significant variables for a chronic GVHD activity index that predicts short-term (provider perception of change, patient perception of change, and changes in immunosuppressive medications) and longer-term outcomes (overall survival, time to discontinuation of systemic immunosuppressive therapy, and functional impairments). This goal will be accomplished by assembling a large modern cohort of people with chronic GVHD at four large core transplant centers. Approximately 700 people (half prevalent cases, half incident cases) with chronic GVHD will be enrolled. Every 3-6 months we will collect both objective and subjective measures reflecting disease activity, response to therapy, detailed physician assessments about organ involvement, and patient self-assessments about symptoms, functional status, and quality of life. Data will be used to test published hypotheses and the new recommendations emanating from the NIH Consensus conference. We will also be able to provide the detailed data needed to understand modern trends in chronic GVHD incidence, manifestations, and response to treatment. These studies are needed to operationalize the recommendations of the NIH Consensus conference, advance our understanding of chronic GVHD, and enhance our ability to conduct clinical trials.

People with chronic GVHD

Inclusion Criteria:

• Age greater than or equal to 2 years
• Prior allogeneic stem cell transplant, with any graft source, donor type, and GVHD prophylaxis allowed
• Clinical or histologic diagnosis of chronic GVHD (overlap syndrome with acute GVHD is allowed
• Need for systemic treatment, defined as any medication or intervention delivered systemically, including extracorporeal photopheresis. If a patient only received topical or local therapy at diagnosis, but subsequently requires systemic treatment, they may be enrolled upon initiation of systemic therapy. (Note, these patients will be classified as incident or prevalent cases depending on time from chronic GVHD diagnosis, not start of systemic therapy)
• If a prevalent case (defined as enrollment three or more months after chronic GVHD diagnosis), then subject must be within 2 years of stem cell infusion
• If an incident case (enrollment less than 3 months after chronic GVHD diagnosis) then no limitation on time from transplantation
• No evidence of primary disease relapseProgression-free for their malignancy at enrollment (no evidence of primary disease progression since transplant, although residual disease may still be present)
• Evaluation at the transplant center at the time of study enrollment
• Signed, informed consent and if applicable, child assent

Exclusion Criteria:

• Inability to comply with study procedures
• Anticipated survival less than 6 months due to co-morbid disease

• University of Minnesota - Clinical and Translational Science Institute
• Stanford University
• Dana-Farber Cancer Institute
• Vanderbilt University
• Medical College of Wisconsin
• Washington University School of Medicine
• H. Lee Moffitt Cancer Center and Research Institute
• Memorial Sloan-Kettering Cancer Center