Sinusoidal Obstruction Syndrome for Stem Cell Transplant Patients Biomarker Study

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.

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.