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Hepatic veno-occlusive disease following sirolimus-based immune suppression

Bone Marrow Transplantation volume 54, pages 85–89 (2019)Cite this article

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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.

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Author contributions

FK, GBMcD and JP contributed in designing the research, data collection, analyzing the data, and writing the manuscript. HS, BB, FL, and HF contributed in research design, critical review, and manuscript writing.

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Authors and Affiliations

  1. BMTCI H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA

    Farhad Khimani, Brian Betts, Frederick Locke, Claudio Anasetti & Joseph Pidala

  2. GI/Hepatology, Fred Hutchinson Cancer Research Center, Seattle, USA

    George B. McDonald

  3. Pathology, University of Washington, Seattle, USA

    Howard M. Shulman

  4. Moffitt Malignant Hematology and Cellular Therapy, Memorial Healthcare System, Florida, USA

    Hugo Fernandez

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  1. Farhad Khimani
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  2. George B. McDonald
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  3. Howard M. Shulman
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  6. Hugo Fernandez
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Correspondence to Farhad Khimani.

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Khimani, F., McDonald, G.B., Shulman, H.M. et al. Hepatic veno-occlusive disease following sirolimus-based immune suppression. Bone Marrow Transplant 54, 85–89 (2019). https://doi.org/10.1038/s41409-018-0233-2

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