Reduced risk of sinusoidal obstruction syndrome of the liver after Busulfan-Cyclophosphamide conditioning prior to allogeneic hematopoietic stem cell transplantation
The aim of this study is to evaluate the incidence of sinusoidal obstruction syndrome (SOS) of the liver and the clinical outcome after hematopoietic stem cell transplantation (HSCT) based on several modifications in our protocols. We retrospectively investigated 372 patients undergoing myeloablative conditioning with oral busulfan and cyclophosphamide before allogeneic HSCT during 1990-2015. Patients' supportive care was changed in order
to reduce the regimen-related toxicities. Norethisterone use was terminated in 1998, therapeutic drug monitoring of busulfan was initiated in 2000 and the use of liver supportive drugs, such as ursodeoxycholic acid (UDCA) and N-acetyl-L-cysteine (NAC), were started in 2002 and 2009, respectively. In total, 26 patients (7.0%) developed SOS at a median of 19 days after transplantation. Of these 26 patients, 20 died at a median of 119 days after HSCT and 102 days after the diagnosis of SOS. The incidence of SOS decreased over time in accordance with the improvements in supportive care. The highest incidence of SOS was during 1995-99 (16.2%) compared to 2.3% during 2010-2015. Overall survival for patients with SOS was 62%, 46% and 27% at 100 days, 1 year and 5 years after HSCT respectively compared to 92%, 77% and 66% for those who did not develop SOS (P<0.001). In conclusion; the incidence of SOS and related deaths were significantly decreased over the last years. Our institution pursues massive preventative and personalized measures for SOS. This strategy may also be applicable in other conditioning protocols in order to reduce the incidence of SOS and hence, improve the clinical outcome.
