Sinusoidal Obstruction Syndrome for Stem Cell Transplant Patients Biomarker Study

Study Overview
=================
Brief Summary
-----------------
The goal of this is to learn more about stem cell transplant and complications that some people have after their transplants, in particular sinusoidal obstruction syndrome (SOS), also called veno-occlusive disease of the liver.

Detailed Description
-----------------
This is a multicenter, prospective, observational trial. We will measure biomarkers and determine thresholds that will predict increased risk for SOS in pediatric patients receiving HCT or high intensity chemotherapy/irradiation with the future goal of a randomized, interventional, open-label, multicenter trial that will test the preemptive use of defibrotide for prevention of SOS in an enriched high-risk population.

Official Title
-----------------
Biomarkers of Endothelial Dysfunction in Pediatric Patients Receiving High Intensity Chemotherapy/Irradiation

Conditions
-----------------
Sinusoidal Obstruction Syndrome

Intervention / Treatment
-----------------
* Other: Serial Blood Draws


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≤ 25 years undergoing HCT for any reason who fulfill any ONE (1) of the following criteria: History of hepatic disease as defined by: Viral hepatitis (i.e., hepatitis C virus [HCV]) Liver tumor before HCT Hepatic fibrosis or cirrhosis before HCT as proven by liver biopsy High aspartate aminotransferase (AST) (> 2x ULN) before HCT (pre-transplant evaluation) High alanine transaminase (ALT) (> 2x ULN) before HCT High bilirubin (> 1.2x ULN) before HCT HCT high-risk features including: a. Conditioning with high-risk modalities including: i. Busulfan (BU)-containing regimen particularly with oral BU + cyclophosphamide ii. TBI-containing regimen, particularly cyclophosphamide + total-body irradiation (TBI) b. ≥ 2 HCT c. Allo-HCT for leukemia > or = second relapse d. Unrelated donor (URD) HCT e. Human leukocyte antigen (HLA) mismatch HCT (less than 10 of 10 for bone marrow/peripheral blood stem cell [BM/PBSC] or anything less than 6 of 6 for UCB) f. Use of sirolimus + tacrolimus prophylaxis for GVHD High-risk disease states including: Juvenile myelo-monocytic chronic leukemia (JMML) Primary hemophagocytic lymphohistiocytosis (HLH) Adrenoleukodystrophy Osteopetrosis Other high-risk features including: Prior treatment with gemtuzumab ozogamicin Use of hepatotoxic drugs 1 month before HCT and during HCT Iron overload (i.e., thalassemia/sickle cell) with serum ferritin > 1000ng/ml Deficit of ATIII, T-PA (i.e., < 30% normal values), and resistance to activated protein C if clinical indication (these values do not have to be specifically checked if no clinical history) Young age < 2 years but more than 1 month Exclusion Criteria: Patients who are transplanted but do not fulfill any of the above mentioned criteria.

Ages Eligible for Study
-----------------
Maximum Age: 25 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Stem Cell Transplant<br>Serial Blood Draws | Other: Serial Blood Draws<br>* Day 0 and Day 3 blood draw for SOS biomarkers. If subject develops SOS blood draw prior to dose of Defibrotide, Day 14 after Defibrotide and Day 21 after Defibrotide.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SOS proteomic markers | Measure for 3 SOS proteomic markers, L-Ficolin, HA, and ST2, as early predictors of SOS incidence through study completion. | Until the end of the study evaluation, day 180 |