Predictive Biomarkers For Pediatric Chronic Graft-Versus-Host Disease

Study Overview
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Brief Summary
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Chronic graft-versus-host disease (cGVHD) can be hard to diagnose, difficult to manage and contributes significantly to morbidity and mortality in hematopoietic stem cell transplantation patients. The research will look into identifying and validating cGVHD biological indicators (=bio-markers) which will be evaluated whether they can predict a future development of the disease. The study hypothesis is that a number of previously reported cGVHD bio-markers, known to be present at the time of cGVHD diagnosis, will also be present at earlier time points, before cGVHD develops. Following validation, the bio-markers will be beneficial for finding those patients who are in higher risk to develop cGVHD. By identifying the higher-risk group, which is more likely to develop cGVHD, a pre-emptive therapy might be applied in order to prevent or reduce the prevalence of the disease.

Official Title
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Applying Biomarkers to Long-term Effects in Child and Adolescent Cancer Treatment (ABLE Team) - Predictive Biomarkers For Pediatric 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: Allogeneic hematopoietic stem cell transplantation for any malignant or non-malignant disease. Age 0-17.99 years at the time of transplantation. Bone marrow, peripheral blood stem cell and umbilical cord blood (including single or double cord blood) as the graft source. Any conditioning regimen with any chemotherapy / radiation therapy combination. Haploidentical donor transplants with post-transplant cyclophosphamide are also allowed. Use of serotherapy is permitted. Any graft-versus-host disease prophylaxis is permitted, including post-HSCT cyclophosphamide. If participant weighs between 0-20 kg, participant must be able to provide 15 ml of whole blood at each time point. If participant weighs over 20 kg, participant must be able to provide 1ml/kg of whole blood, up to a maximum of 23 mL for the pre-conditioning sample and 32 mL for samples at day +100, 6-months, 12-months, +/- the cGVHD sample. Written informed consent from parents. Assent from study participant when appropriate. Participation on other clinical trials is acceptable. Exclusion Criteria: Autologous HSCT. Patients referred to a Bone Marrow Transplant (BMT) center from a non-BMT center, where it is anticipated (at the discretion of the center PI) that adequate follow up according to the rules of this protocol can not be met, including the requirement for a reassessment by the BMT center at the time of cGVHD diagnosis. Ex-vivo T-cell depletion of graft source (e.g. CD34 selection). Second (or greater) allogeneic transplants (first allogeneic transplant where a previous autologous transplant was performed is permitted). Syngeneic transplants.

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of predictive bio-markers for pediatric chronic Graft-Versus-Host Disease (cGVHD) in Hematopoietic Stem Cell Transplant (HSCT) recipients | The study will try to determine the prevalence (or levels) of high-probability predictive plasma and cellular cGVHD bio-markers in pediatric patients undergoing allogeneic HSCT from blood samples | Just before transplant to 12 months post transplant or until diagnosis of cGVHD if precede the 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Validation of predictive cGVHD bio-markers | To determine and validate whether predictive cGVHD bio-markers present before the onset of cGVHD are able to predict a subset of pediatric patients at greatest risk for the development of cGVHD in the future | Measure will be assessed following the submission of all samples. During the last year of the study (Oct. 2016 - Sept. 2017) |