Analysis of the Incidence and Characteristics of Venoocclusive Disease (VOD) of the Liver in Pediatric Hematopoietic Progenitor Cell Transplant (HPCT) Patients with Heparin Alone Vs. Heparin and Ursodiol Prophylaxis at the Medical College of Wisconsin.
Authors: Talano Julie-An , Brown Jessica , McArthur Jennifer , Mulberry Mollie , Eastwood Daniel , Ahn Kwang Woo , Casper James T. , Margolis David 
Published: October 2019

Abstract 4306

VOD is a serious and potentially life-threatening complication of HPCT as a result of liver injury from the effect of chemotherapy and/or radiation. The reported incidence rate in pediatric HPCT patients varies widely from 5% to 40%. Previous studies have shown the beneficial effects of post-transplant pharmacological therapies such as ursodeoxyholic acid (ursodiol), heparin, and defibrotide at preventing VOD. However, the combined effect of heparin and ursodiol prophylaxis in preventing VOD in pediatric patients has yet to be determined. This study evaluated retrospectively whether there was a benefit of such combined therapy in pediatric HPCT patients. Our center adopted as standard practice for all HPCT patients the initiation of low dose heparin at 4 units/kg/hour with the commencement of conditioning for HPCT until day +28 post transplant. In 2003, we combined ursodiol 10 mg/kg TID to start with HPCT conditioning and to continue until day + 100 post transplant with low dose heparin through day + 28 for all pediatric HPCT patients. We performed a retrospective chart review and compared the characteristics and the incidence of VOD in patients who underwent transplantation from 1996-2002 and received heparin alone compared to 2003-2008 when the patients received the combination of heparin and ursodiol prophylaxis. Patients were identified through medical records with the ICD diagnosis of VOD. The medical records were reviewed and those patients who did not meet the Baltimore criteria for the diagnosis of VOD were excluded. Only patients who developed VOD with their first transplants were included.

Group I = Heparin (216) Group II = Heparin + Ursodiol (220) Allogeneic 187 (86.5%) 160 (72.7%) Autologous 29 (13.5%) 60 (27.3%) Median Age 9 yrs 8 yrs Male 123 (57%) 135 (62%) Female 93 (43%) 85 (38%) Non-malignant 34 (15.7%) 50 (22.8%) Hematologic malignancy 143 (66.2%) 109 (49.5%) Non-hematologic malignancy 39 (18.1%) 61 (27.7%) # VOD 13 5

The 100 day incidence of VOD was 0.0605 (SE 0.01618) in group 1 and 0.0227 (SE 0.01002) in group 2. The difference is 0.0377 (SE 0.0190) and based on a standard normal distribution with a p = 0.0473. The estimated risk of VOD for patients receiving Heparin + Ursodiol is 0.94 (risk or hazard ratio) that of the risk with Heparin alone, with a 95% confidence interval of (0.918, 0.960). This represents about a 6% reduction in risk for those receiving Heparin + Ursodiol. The day 100 survival in the VOD patients was 6 out of 13 in group 1 and 3 out of 5 in group 2. In conclusion, low dose heparin and ursodiol prophylaxis appears to be an effective strategy in VOD prevention in pediatric patients. The combination appeared to be more effective than heparin alone. However, this study is limited in that it is retrospective in nature.

Disclosures:

Off Label Use: heparin and ursodiol as VOD prophylaxis.