This study will examine the natural history of chronic graft-versus-host disease, a complication of blood or bone marrow stem cell transplant treatments. Patients with cancers of the blood and immune system can sometimes benefit greatly from, and even be cured by, transplants of stem cells (cells produced by the bone marrow that mature into blood cells). In addition to producing new bone marrow and restoring normal blood production and immunity, the donated cells fight any residual tumor cells that might have remained in the body. However, donated immune system cells called T cells sometimes attack healthy tissues in a reaction called graft-versus-host-disease (GVHD). Chronic GVHD (cGVHD) is one of the most serious complications of stem cell transplants. It can affect almost any part of the body, especially the skin, mouth, liver, gut, and eyes. A better understanding of cGVHD may lead to improved treatments.

Patients from 1 to 75 years of age with cGVHD or signs of the disease may be eligible for this study.

Participants undergo the following baseline tests and procedures: medical history and physical examination, including blood and urine tests; pulmonary function tests; bone density scan; biopsy (surgical removal of a small tissue sample) of the affected organ; consultations with a nutritionist, physical therapist, pain specialist, eye doctor, social worker, gynecologist (for women), skin doctor, and dentist; saliva collection (in patients 8 years of age and older); nutritional habits questionnaire (in patients 18 years of age and older); quality of life questionnaire (in patients 8 years of age and older). At the end of the baseline evaluations, patients and their doctors are provided a summary of the test results and treatment recommendations.

Some patients may undergo some of the following additional procedures: consultations with specialists in kidney disease, psychiatry, neurology, liver disease, endocrine disorders, lung disease, infectious diseases, rheumatology, or others; imaging studies that may include chest x-ray, chest computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, photographs if the skin is affected; biopsy of the affected organ, of the tumor in patients with a co-existing cancer that is not in remission, or of the bone marrow in patients with abnormal blood counts; upper or lower (or both) gastrointestinal (GI) endoscopy in patients with GI symptoms; bronchoalveolar lavage in patients with lung symptoms; leukapheresis, a procedure to obtain quantities of white blood cells (in patients 18 years of age and older); skin or mouth mucosa or lip biopsy (only patients 18 years of age and older); ultrasound in patients with a scleroderma-type GVHD (hardening of the skin) or fascitis (muscle inflammation); MRI in patients with a scleroderma-type GVHD (hardening of the skin) or fascitis (muscle inflammation).

Patients are followed by telephone at 6, 12, 18, 24, 30, and 36 months, and then yearly for 10 years to check on their health status. In addition, they are mailed quality of life questionnaires yearly to complete and return. Some patients may be asked to return to the clinic for follow-up evaluations that may include one or more of the following: blood draw, biopsy, saliva sample, and ultrasound. Additional procedures that may be performed only on patients 18 years of age and older include an extra skin or mucosal biopsy, leukapheresis, and MRI.

Further Study Details: 

Expected Total Enrollment:  170

Chronic graft-versus-host disease (cGVHD) is a multi-organ alloimmune and autoimmune disorder that occurs following allogeneic hematopoietic stem cell transplantation (alloHSCT). It is characterized by immune dysregulation, immunodeficiency, impaired organ function, and decreased survival. Each year about 7000 patients receive allogeneic hematopoietic stem cell transplant (alloHSCT) in North America and about 50% of patients who are transplanted develop cGVHD. Chronic GVHD is also a disorder that simultaneously affects many organ systems in highly variable fashion and requires complex and coordinated medical management by multiple medical specialties. There is an urgent need for progress in understanding and effective treatments for cGVHD as it is one of the most serious complications of cancer therapy and hematopoietic stem cell transplantation.

The primary objective of this protocol is to establish a multidisciplinary clinic infrastructure for study of the pathogenesis and natural history of cGVHD. In addition to providing a vehicle for enrollment of patients with chronic GVHD on NCI and NIH protocols, this study has several secondary objectives: a) To prospectively identify clinical and biological prognostic markers in patients with cGVHD; b) To develop clinically relevant cGVHD grading scales; c) To identify novel biological characteristics of cGVHD and to describe them in the context of clinical history and presentation; d) To identify potential clinical and biological markers of cGVHD activity; e) To improve understanding of the biology of cGVHD-associated graft-versus-tumor effects.

This is a non-therapeutic study emphasizing cross sectional and longitudinal data collection. The aim of data analysis is primarily hypothesis-generating. For study purposes, clinical data collection time points are scheduled every six months during the first three years of the study and then yearly. A total of 170 subjects will be enrolled onto this protocol and it is anticipated that this enrollment will take 4-5 years. The benefits from this protocol to the patients include undergoing a thorough multi-disciplinary evaluation and consultation by the cGVHD clinical team, including assessment and treatment recommendations. Patients enrolled in this natural history protocol will also be referred to experimental treatment protocols when appropriate. Risks are those of clinically indicated evaluations, as well as risks associated with research blood draws, imaging studies, and biopsies (defined and consented individually). Patient confidentiality will be protected and, with permission, information will be freely shared with the referring/treating physicians.

Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

INCLUSION CRITERIA:
Any patient age 1-75 referred by the primary transplant physician for the evaluation of chronic graft-versus-host disease independently of age or underlying diagnosis;
Patient or the patient's legal representative is able and willing to provide consent.
EXCLUSION CRITERIA:
Significant medical condition or any other significant circumstance that could in the PIs assessment affect the patient's ability to tolerate, comply, or complete the study;
Patients who in the PIs assessment have a life expectancy less than 3 months.
Because it is not always possible to make a clear clinical distinction between acute and chronic GVHD, patients with acute GVHD are not a-priori excluded until the possibility of chronic GVHD is reliably excluded on the basis of the clinical assessments in the cGVHD clinic.

Maryland
      National Cancer Institute (NCI), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  040281; 04-C-0281
Record last reviewed:  September 7, 2004
Last Updated:  December 13, 2004
Record first received:  September 21, 2004
ClinicalTrials.gov Identifier:  NCT00092235
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08