Improving Outcomes Assessment in Chronic GVHD

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.

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