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Hepatic veno-occlusive disease following sirolimus-based immune suppression.
Bone Marrow Transplant. 2019 01; 54(1):85-89.BM

Abstract

Sirolimus-based graft vs. host disease (GVHD) prophylaxis is associated with higher incidence of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) after allogeneic hematopoietic cell transplantation (HCT). However, whether the clinical manifestations and prognosis of VOD/SOS differs when diagnosed in the setting of sirolimus-based GVHD prophylaxis is not well studied. To address this question, we examined presenting features and treatment outcome of VOD/SOS cases identified in a large retrospective cohort of consecutive HCT procedures (n = 818 total, sirolimus (SIR)/tacrolimus (TAC) n = 308, and methotrexate (MTX) or mycophenolate mofetil (MMF)/TAC n = 510). In multivariate analysis, sirolimus-based GVHD prophylaxis (p = 0.006, HR 3.33, 1.94-5.7) increased risk for VOD/SOS. A total of 58 patients were clinically diagnosed with VOD/SOS (SIR/TAC 38/308, 12.3%, vs. MTX or MMF/TAC 20/510, 3.9%). VOD/SOS diagnosed following SIR/TAC prophylaxis demonstrated later time of onset (median 39 vs. 26 days; p = 0.005), less severe hyperbilirubinemia (Bili > 2, 65% vs. 90% p = 0.04), lesser degree of weight gain (weight gain > 5%, 52% vs 80%, p = 0.04), and more frequent complete resolution of hepatic injury (79% vs. 55%, p = 0.05). Presenting features and natural history of VOD/SOS in the context of SIR/TAC GVHD prophylaxis differ and thus warrant particular clinical attention to later hepatic injury in these patients.

Authors+Show Affiliations

BMTCI H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA. Farhad.Khimani@moffitt.org.GI/Hepatology, Fred Hutchinson Cancer Research Center, Seattle, USA.Pathology, University of Washington, Seattle, USA.BMTCI H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA.BMTCI H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA.Moffitt Malignant Hematology and Cellular Therapy, Memorial Healthcare System, Florida, USA.BMTCI H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA.BMTCI H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA.

Pub Type(s)

Clinical Trial
Journal Article
Observational Study

Language

eng

PubMed ID

29895929

Citation

Khimani, Farhad, et al. "Hepatic Veno-occlusive Disease Following Sirolimus-based Immune Suppression." Bone Marrow Transplantation, vol. 54, no. 1, 2019, pp. 85-89.
Khimani F, McDonald GB, Shulman HM, et al. Hepatic veno-occlusive disease following sirolimus-based immune suppression. Bone Marrow Transplant. 2019;54(1):85-89.
Khimani, F., McDonald, G. B., Shulman, H. M., Betts, B., Locke, F., Fernandez, H., Anasetti, C., & Pidala, J. (2019). Hepatic veno-occlusive disease following sirolimus-based immune suppression. Bone Marrow Transplantation, 54(1), 85-89. https://doi.org/10.1038/s41409-018-0233-2
Khimani F, et al. Hepatic Veno-occlusive Disease Following Sirolimus-based Immune Suppression. Bone Marrow Transplant. 2019;54(1):85-89. PubMed PMID: 29895929.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hepatic veno-occlusive disease following sirolimus-based immune suppression. AU - Khimani,Farhad, AU - McDonald,George B, AU - Shulman,Howard M, AU - Betts,Brian, AU - Locke,Frederick, AU - Fernandez,Hugo, AU - Anasetti,Claudio, AU - Pidala,Joseph, Y1 - 2018/06/12/ PY - 2018/03/26/received PY - 2018/04/30/accepted PY - 2018/04/20/revised PY - 2018/6/14/pubmed PY - 2020/1/23/medline PY - 2018/6/14/entrez SP - 85 EP - 89 JF - Bone marrow transplantation JO - Bone Marrow Transplant. VL - 54 IS - 1 N2 - Sirolimus-based graft vs. host disease (GVHD) prophylaxis is associated with higher incidence of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) after allogeneic hematopoietic cell transplantation (HCT). However, whether the clinical manifestations and prognosis of VOD/SOS differs when diagnosed in the setting of sirolimus-based GVHD prophylaxis is not well studied. To address this question, we examined presenting features and treatment outcome of VOD/SOS cases identified in a large retrospective cohort of consecutive HCT procedures (n = 818 total, sirolimus (SIR)/tacrolimus (TAC) n = 308, and methotrexate (MTX) or mycophenolate mofetil (MMF)/TAC n = 510). In multivariate analysis, sirolimus-based GVHD prophylaxis (p = 0.006, HR 3.33, 1.94-5.7) increased risk for VOD/SOS. A total of 58 patients were clinically diagnosed with VOD/SOS (SIR/TAC 38/308, 12.3%, vs. MTX or MMF/TAC 20/510, 3.9%). VOD/SOS diagnosed following SIR/TAC prophylaxis demonstrated later time of onset (median 39 vs. 26 days; p = 0.005), less severe hyperbilirubinemia (Bili > 2, 65% vs. 90% p = 0.04), lesser degree of weight gain (weight gain > 5%, 52% vs 80%, p = 0.04), and more frequent complete resolution of hepatic injury (79% vs. 55%, p = 0.05). Presenting features and natural history of VOD/SOS in the context of SIR/TAC GVHD prophylaxis differ and thus warrant particular clinical attention to later hepatic injury in these patients. SN - 1476-5365 UR - https://www.unboundmedicine.com/medline/citation/29895929/Hepatic_veno_occlusive_disease_following_sirolimus_based_immune_suppression_ L2 - http://dx.doi.org/10.1038/s41409-018-0233-2 DB - PRIME DP - Unbound Medicine ER -