1.
Prognostic Biomarkers for Hepatic Veno-occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS) in Myeloablative Allogeneic Hematopoietic Cell Transplantation: Results from the BMT CTN 1202 Study
Putta, S., Young, B. A., Levine, J. E., Reshef, R., Nakamura, R., Strouse, C., Perales, M. A., Howard, A., Pine, P., Shi, J., et al
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of hematopoietic cell transplantation (HCT). OBJECTIVES To determine a blood biomarker signature early after HCT that identifies patients at high risk for VOD/SOS. STUDY DESIGN A set of 23 plasma biomarkers, selected from the VOD/SOS literature, was measured on Days 0, 7, and 14 after myeloablative HCT using blood samples from patients enrolled in the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Protocol 1202. Eligible cases were diagnosed with VOD/SOS in BMT CTN 1202 using Baltimore criteria. Controls (without VOD/SOS) were matched to cases for conditioning regimen and age. Significant biomarkers were identified using Bonferroni-adjusted Wilcoxon rank sum (P≤0.002). RESULTS 33 patients with mild or severe VOD/SOS were identified (cases) and matched to 107 controls. Two, eight, and five biomarkers measured from the plasma of these patients were significantly associated with development of VOD/SOS at Days 0, 7, and 14, respectively, with the strongest associations being on Days 7 and 14. Biomarker associations were stronger for severe VOD/SOS risk and were stronger prognostic markers for VOD/SOS cases occurring within 28 days of HCT. Hyaluronan was most strongly associated with VOD/SOS risk, with an area under the receiving operator curve (AUC) of 0.81 on Day 7 and 0.79 on Day 14. Multivariate models of up to five biomarkers generated AUCs ranging from 0.82 to 0.85. All associations with VOD/SOS risk were independent of clinical risk factors. CONCLUSIONS This study confirmed previously identified biomarkers of VOD/SOS risk and identified novel, prognostic biomarker signatures that identify patients at risk for VOD/SOS shortly after HCT. Multivariate analysis suggests that a combination of up to five of these protein biomarkers may provide a prognostic tool for identifying patients at risk for VOD/SOS.
2.
Low-dose unfractionated heparin prophylaxis is a safe strategy for the prevention of hepatic sinusoidal obstruction syndrome after myeloablative adult allogenic stem cell transplant
Sola, M., Bhatt, V., Palazzo, M., Cavalier, K. E., Devlin, S. M., Maloy, M., Barker, J. N., Castro-Malaspina, H., Chung, D., Dahi, P. B., et al
Bone marrow transplantation. 2022
Abstract
Hepatic sinusoidal obstruction syndrome (SOS) is a serious complication after allogeneic stem cell transplantation (allo-HCT). However, there is no uniform consensus on the optimal strategy for SOS prevention. Ursodeoxycholic acid is the most used regimen, even though its administration is challenging in recipients unable to tolerate oral medication. Defibrotide was recently studied in a phase 3 trial, but enrollment was stopped early due to futility. Low-dose unfractionated heparin (UFH) is an alternative strategy. However, its efficacy is reputed but unproven increased risk of bleeding has not been fully established. We evaluated 514 adult allo-HCT recipients who received SOS prophylaxis with low-dose UFH. Bleeding complications occurred in 12 patients 2.3% of patients of which only 2 (0.4%) had significant grade 3 bleeding. Only 14 patients were diagnosed with hepatic SOS. Univariate analysis showed that day 100 SOS was higher in recipients of unmodified grafts when compared to CD34+ selected ex vivo T-cell depleted grafts (p ≤ 0.001), and patients with hepatitis B and/or C exposure pre-HCT (p = 0.028). Overall, UFH was well tolerated and associated with a low incidence of subsequent hepatic SOS. Low-dose UFH prophylaxis can be considered in select patients who cannot tolerate oral ursodiol.