STUDY OBJECTIVES: To determine the frequency of sinusoidal obstructive syndrome (SOS) in patients undergoing allogeneic hematopoietic cell transplantation who received graft-versus-host disease (GVHD) prophylaxis with sirolimus and tacrolimus, and to assess whether the occurrence of SOS correlates with immunosuppressant levels. DESIGN: Retrospective cohort study. SETTING: Hematopoietic cell transplant unit at an academic medical center. PATIENTS: Fifty-nine adults who received myeloablative preparative regimens for transplantation of any hematologic malignancy and received sirolimus and tacrolimus for GVHD prophylaxis between January 1, 2007, and May 1, 2009; all donors and transplant recipients were human leukocyte antigen (HLA) matched for at least HLA-A, -B, -C, and -DRB1. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the occurrence of SOS after hematopoietic cell transplantation. Plasma concentrations of sirolimus and tacrolimus and the summative levels of sirolimus and tacrolimus were then compared in patients who developed SOS with those who did not develop SOS. Trough levels were measured from blood samples collected 30-60 minutes before the morning doses of sirolimus and tacrolimus on days 0-35, or until the development of SOS. Of the 59 patients, 12 (20%) developed SOS. The mean sirolimus level was significantly higher in patients who developed SOS relative to those who did not develop SOS (10.5 vs 8.7 ng/ml, p=0.003). The mean summative trough level of sirolimus and tacrolimus was also significantly higher in those who developed SOS compared with those who did not (19.7 vs 17.1 ng/ml, p=0.003). The mean ± SD time to the occurrence of SOS was 28 ± 8.7 days. The median time to death was 101 days for patients who developed SOS compared with 433 days for patients who did not develop SOS (p=0.002). CONCLUSION: Sirolimus plasma concentration may correlate with the development of delayed SOS; however, further research is needed to prospectively evaluate the role of sirolimus exposure in the pathogenesis of SOS.
STUDY OBJECTIVES: To determine the frequency of sinusoidal obstructive syndrome (SOS) in patients undergoing allogeneic hematopoietic cell transplantation who received graft-versus-host disease (GVHD) prophylaxis with sirolimus and tacrolimus, and to assess whether the occurrence of SOS correlates with immunosuppressant levels. DESIGN: Retrospective cohort study. SETTING: Hematopoietic cell transplant unit at an academic medical center. PATIENTS: Fifty-nine adults who received myeloablative preparative regimens for transplantation of any hematologic malignancy and received sirolimus and tacrolimus for GVHD prophylaxis between January 1, 2007, and May 1, 2009; all donors and transplant recipients were human leukocyte antigen (HLA) matched for at least HLA-A, -B, -C, and -DRB1. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the occurrence of SOS after hematopoietic cell transplantation. Plasma concentrations of sirolimus and tacrolimus and the summative levels of sirolimus and tacrolimus were then compared in patients who developed SOS with those who did not develop SOS. Trough levels were measured from blood samples collected 30-60 minutes before the morning doses of sirolimus and tacrolimus on days 0-35, or until the development of SOS. Of the 59 patients, 12 (20%) developed SOS. The mean sirolimus level was significantly higher in patients who developed SOS relative to those who did not develop SOS (10.5 vs 8.7 ng/ml, p=0.003). The mean summative trough level of sirolimus and tacrolimus was also significantly higher in those who developed SOS compared with those who did not (19.7 vs 17.1 ng/ml, p=0.003). The mean ± SD time to the occurrence of SOS was 28 ± 8.7 days. The median time to death was 101 days for patients who developed SOS compared with 433 days for patients who did not develop SOS (p=0.002). CONCLUSION:Sirolimus plasma concentration may correlate with the development of delayed SOS; however, further research is needed to prospectively evaluate the role of sirolimus exposure in the pathogenesis of SOS.
Authors: Vaibhav Agrawal; Praveen Ranganath; Kirsten D Ervin; Caitlin A Schmidt; Elizabeth A Cox; Robert P Nelson; Jennifer E Schwartz; Mohammad Abu Zaid; Rafat Abonour; Michael J Robertson; Bryan J Brinda; Shawn P Griffin; Teresa C Thakrar; Sherif S Farag Journal: Bone Marrow Transplant Date: 2020-07-04 Impact factor: 5.483
Authors: Juan Montoro; José Luis Piñana; Carlos Solano; Jaime Sanz; Juan C Hernández-Boluda; Rafael Hernani; Ignacio Lorenzo; Ariadna Pérez; Manuel Guerreiro; Aitana Balaguer-Rosello; Guillermo F Sanz; Carlos Carretero; Eliseo Albert; David Navarro; Miguel A Sanz Journal: Bone Marrow Transplant Date: 2020-05-05 Impact factor: 5.483