Patient case: 64-year-old male with bladder cancer; genetic feature: FGFR3 (S249C)

Clinical trial: Factors Determining Outcomes in Patients With Graft-Versus-Host Disease

Summary: 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 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.
  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.
  Eligibility:
  -Patients age 1-75 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 labotory 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 every six months during the first three years of the study and then yearly.

Detailed description: 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 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.
  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;
  Eligibility:
  -Patients age 1-75 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 every six months during the first three years of the study and then yearly.

Eligibility: -  INCLUSION CRITERIA:
  1. 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;
  2. Patient or the patient's legal representative is able and willing to provide consent.
  EXCLUSION CRITERIA:
  1. 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;
  2. 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.

Relevance to patient case: not relevant