Low molecular weight heparin for the prevention of hepatic veno-occlusive disease (VOD) after hematopoietic stem cell transplantation: a prospective phase II study

• Published in: Bone marrow transplantation (Basingstoke) Vol. 31; no. 12; pp. 1143 - 1149
• Main Authors: FORREST, D. L, THOMPSON, K, DORCAS, V. G, COUBAN, S. H, PIERCE, R
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.06.2003; Nature Publishing Group UK
• Subjects: Adolescent; Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Anticoagulants; Arterial occlusions; Autografts; Biological and medical sciences; Bleeding; Bone marrow; Bone marrow, stem cells transplantation. Graft versus host reaction; Complications and side effects; Dalteparin - administration & dosage; Dalteparin - adverse effects; Disease prevention; Female; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic stem cells; Hemorrhage - chemically induced; Heparin; Hepatic Veno-Occlusive Disease - etiology; Hepatic Veno-Occlusive Disease - prevention & control; Humans; Injections, Subcutaneous; Liver diseases; Low molecular weights; Male; Medical sciences; Middle Aged; Molecular weight; Patients; Prevention; Prophylaxis; Prospective Studies; Radiation therapy; Renal failure; Safety; Stem cell transplantation; Stem cells; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Transplantation, Autologous; Transplantation, Homologous; Veno-occlusive disease; Human; Venoocclusive disease; Stem cell; Liver; Hematopoietic cell; Homograft; Cardiovascular disease; Hepatic disease; Low molecular weight heparin; Anticoagulant; VOD; Venous disease; Prevention; Autograft; Chemotherapy; Treatment; Phase II trial; Digestive diseases; Graft; Complication; Glycosaminoglycan; Heparin
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/sj.bmt.1704087

We evaluated 40 patients undergoing high-dose chemo/radiotherapy (HDCT) and hematopoietic stem cell transplantation (HSCT) (allogeneic (22), autologous (18)) to determine the safety and feasibility of administering low molecular weight heparin (LMWH) as hepatic veno-occlusive disease (VOD) prophylaxis. Patients received a once daily subcutaneous injection of dalteparin 2500 anti-Xa i.u. commencing the day prior to starting HDCT, and continuing until day +30 post HSCT or hospital discharge, whichever came first. Dosage adjustments were made for patients developing renal failure. All bleeding episodes were recorded and graded and VOD was diagnosed and graded according to Seattle criteria. At 100 days of follow-up, the overall survival and probability of regimen-related mortality were 85 and 15%, respectively. Nine patients developed VOD. The probability of developing VOD post allogeneic and autologous HSCT was 28% (95% CI, 6-45) and 17% (95% CI, 0-32), respectively. VOD was graded as moderate (n=8) and severe (n=1). VOD resolved in all cases except for one patient who died secondary to severe VOD and multiorgan failure. Clinically significant bleeding episodes occurred in three patients; 24 patients developed minor bleeding not requiring specific therapy. All bleeding episodes resolved. These results suggest that LMWH for VOD prophylaxis is safe with a low incidence of serious bleeding events. Whether it is superior to unfractionated heparin, however, is unknown and should be addressed within the context of a randomized controlled trial.