Natural History Study of Clinical and Biological Factors Determining Outcomes in Chronic Graft-Versus-Host Disease

Study Overview
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Brief Summary
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Background: 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 8000 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. Objectives: To establish a multidisciplinary clinic infrastructure for study of the pathogenesis and natural history of cGVHD. To prospectively identify clinical and biological prognostic markers in patients with cGVHD To develop clinically relevant cGVHD grading scales To identify novel biological characteristics of cGVHD and to describe them in the context of clinical history and presentation To identify potential clinical and biological markers of cGVHD activity To improve understanding of the biology of cGVHD-associated graft-versus-tumor effects To identify potential patients for cGVHD treatment protocols at the NCI and NIH Eligibility: -Patients age 1 and older referred by the primary transplant physician for the evaluation of chronic graft-versus-host disease independent of underlying diagnosis. Design: Patient undergoes initial clinical and laboratory multispecialty work-up at the NCI cGVHD clinic. Minimally invasive biopsies and rarely, deep tissue biopsy may be obtained to confirm the diagnosis and/or rule-out other pathologic process (in adults only). Long tem data collection for evaluation of long-term outcomes will be conducted anually as feasible

Detailed Description
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Background: 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 8000 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. Objectives: To establish a multidisciplinary clinic infrastructure for study of the pathogenesis and natural history of cGVHD. To prospectively identify clinical and biological prognostic markers in patients with cGVHD To develop clinically relevant cGVHD grading scales To identify novel biological characteristics of cGVHD and to describe them in the context of clinical history and presentation To identify potential clinical and biological markers of cGVHD activity To improve understanding of the biology of cGVHD-associated graft-versus-tumor effects To identify potential patients for cGVHD treatment protocols at the NCI and NIH Eligibility: -Patients age 1 and older referred by the primary transplant physician for the evaluation of chronic graft-versus-host disease independent of underlying diagnosis. Design: Patient undergoes initial clinical and laboratory multispecialty work-up at the NCI cGVHD clinic. Minimally invasive biopsies and rarely, deep tissue biopsy may be obtained to confirm the diagnosis and/or rule-out other pathologic process (in adults only). Long tem data collection for evaluation of long-term outcomes will be conducted anually as feasible

Official Title
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Natural History Study of Clinical and Biological Factors Determining Outcomes in Chronic Graft-Versus-Host Disease

Conditions
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Chronic Graft vs. Host Disease

Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Any patient age 1 and older 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. Note: 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. Pregnant women are excluded from this study because multiple tests would need to be excluded for safety of the patient and the fetus.

Ages Eligible for Study
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Minimum Age: 1 Year

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort 1<br>Patients who have undergone an allogeneic stem cell transplant and are diagnosed with cGVHD | |
| Cohort 2<br>Pediatric patients who have undergone an allogeneic stem cell transplant and are diagnosed with cGVHD | |
| Cohort 3<br>Patients who have undergone an allogeneic stem cell transplant and choose to submit biopsy, blood and urine samples only | |
| Cohort 4<br>Patients who have undergone an allogeneic stem cell transplant and are not diagnosed with cGVHD | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To prospectively identify candidate markers for clinical and biological prognostic factors in patients with cGVHD and develop a prognostic model | Patient evaluations resulting in collection of data via several medical specialties; data will be examined individually and against clinical outcomes. | 2 years + 3 months after protocol entry | 
| To improve our current understanding of the biology of cGVHD-associated graft-versus-tumor effects (GVT). | Studying mechanisms of how cGVHD exerts its anti-cancer effects via laboratory analysis. | ongoing | 
| To identify potential clinical and biological markers of cGVHD activity | Assessment of risk and outcome as related to molecular markers of pathogenesis and/or stage of disease. | ongoing | 
| To identify novel biological characteristics of cGVHD and to describe them in the context of clinical history and presentation | Through collection of data via several medical specialties, assess the weight of specific clinical and biological characteristics and disease severity scales for predicting major clinical outcomes. | ongoing | 
| To establish a multidisciplinary clinic infrastructure for study of pathogenesis and natural history of cGVHD | Assessment of clinical and biological characteristics of cGVHD. | ongoing | 
| To develop clinically relevant cGVHD grading scales | Develop appropriate staging as a tool for measuring responses or outcomes in clinical studies through prospective collection and analysis of data. | ongoing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cGVHD-associated graft-versus-tumor effects (GVT), Allo-HSCT controls, Leukapheresis, Natural History