EBV-Related PTLD, Heart Transplant, Kidney Transplant, Liver Transplant, PTLDs, Small Intestine Transplant
Conditions
Keywords
Biomarkers, Post-Transplant Lymphoproliferative Disorders (PTLDs)
Brief summary
Solid organ transplantation is an important therapeutic option for children with a variety of end stage diseases. However, the same immunosuppressive medications that are required to prevent the child's immune system from attacking and rejecting the transplanted organ can predispose these individuals to developing a very serious cancer that is linked to Epstein-Barr virus (EBV).
Detailed description
EBV-associated post-transplant lymphoproliferative disease (PTLD) is the most common malignancy in children after transplant. Diagnosis and effective treatment of the EBV-associated cancer is hampered by our inability to determine which children are at risk of developing these cancers and to detect the cancer at an early stage. In this study, we plan to test new biomarkers in the blood of children that will tell us very early on if the child is at risk of developing the EBV-associated cancer or if the cancer is present. These studies provide new opportunities for detection, diagnosis, and treatment of children with EBV-associated, post-transplant cancer.
Interventions
PROCEDUREtransplant
All subjects enrolled in this study are candidates for/recipients of solid organ transplants as a therapeutic for end stage diseases (e.g., heart, liver, heart with liver, kidney, small intestine, or liver with small intestine transplants).
DRUGImmunosuppressive Drugs
Immunosuppressive drugs prescribed as standard of care to prevent rejection of the allograft.
Sponsors
Clinical Trials in Organ Transplantation in Children
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
No minimum to 21 Years
Healthy volunteers
No
Inclusion criteria
* Subject and/or parent or legal guardian must be able to understand and provide informed consent/assent; * Candidate for or recipient of: heart, liver, heart with liver, small intestine, liver with small intestine, or kidney; and * Subject enrolled within 3 years of transplant.
Exclusion criteria
* Previous diagnosis of PTLD; * Transplant recipients of lung alone, or in combination with an eligible organ type; * Pancreas transplantation with the exception of 'en bloc' transplant in combined liver and small intestine multivisceral transplantation; * Any combination other than listed in inclusion criteria; * History of any previous solid organ, stem cell, or bone marrow transplantation; * Inability or unwillingness of the legal guardian and/or the subject to comply with the study protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Epstein-Barr Virus (EBV) Positive Post-Transplant Lymphoproliferative Disorders (PTLD) | Receipt of transplanted organ(s) to confirmation of EBV-positive PTLD, up to year 4 post - enrollment | The development of EBV positive PTLD during the study period as assessed by the local site pathologist, with confirmation of the PTLD diagnosis by the Study Clinicopathological Review Board (SCPRB) |
| Specified Gain-of-Function Mutations in EBV Latent Membrane Protein 1 (LMP-1) | Receipt of transplanted organ(s) to confirmation of mutations in EBV LMP1 , up to year 4 post - enrollment | Specified gain-of-function mutations in EBV LMP-1 (e.g., corresponding to EBV LMP-1 variants G212S or S366T) detected by polymerase chain reaction (PCR) method |
| Pathogenic Changes in B Cell Clonotype Development | Receipt of transplanted organ(s) to confirmation of changes in B cell clonotype development, up to year 4 post - enrollment | Pathogenic changes in B cell clonotype development as assessed using high throughput sequencing (HTS) |
Countries
United States
Outcome results
None listed