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Treatment of hepatitis C in a pediatric patient using simeprevir and sofosbuvir immediately after an umbilical cord blood transplantation

Bone Marrow Transplantation volume 51, pages 735–737 (2016)Cite this article

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The prevalence of hepatitis C virus (HCV) infection in hematopoietic stem cell transplantation (HSCT) recipients has been estimated to be approximately 6%.1 Studies have consistently demonstrated that HCV infection increases the risk for early non-relapse mortality after HSCT.2, 3, 4 HCV-infected HSCT recipients are more likely to develop sinusoidal obstruction syndrome (SOS), graft-versus-host disease (GvHD), hepatic inflammation and fatal liver failure compared with non-HCV-infected HSCT recipients. Long term, there is also an increased risk for developing cirrhosis and hepatocellular carcinoma at an accelerated rate.1, 5, 6 The standard therapy for HCV infections has been pegylated IFN-α and ribavirin.7 IFN-α and ribavirin therapy is poorly tolerated and the efficacy is suboptimal with only ~50% of HSCT patients achieving a sustained viral response.8 In 2013, the Food and Drug Administration approved two direct acting antivirals (DAAs), simeprevir and sofosbuvir, for treatment of HCV. Simeprevir is an NS3/4A protease inhibitor and sofosbuvir is a nucleotide-analog NS5B polymerase inhibitor. The once daily oral DAAs have been reported to be well tolerated.9 Combined, 92% of HCV-infected non-HSCT adults attained a sustained viral response in a randomized trial.9 DAAs have the potential to significantly change the natural course of HCV infection in HSCT recipients.10 Although new guidelines for the diagnosis and management of HCV infection in HSCT recipients are becoming available, information regarding DAAs in pediatric patients undergoing HSCT remains sparse.7, 10 We present a case of an HCV-infected pediatric patient who was treated with simeprevir and sofosbuvir immediately following an umbilical cord blood transplantation.

The patient underwent an unrelated four of six HLA matched umbilical cord blood (UCB) transplantation with a total nucleated cell dose of 10.6 × 107 total nucleated cells/kg. HLA antigen mismatches were at HLA-A and HLA-B loci (patient: A*32:01; B*08:01 and UCB: A*3:01; B*49:01). A standard myeloablative preparative regimen of TBI (13.2 Gy), cyclophosphamide (120 mg/kg) and fludarabine (75 mg/m2) was modified to reduce the fractionated total body irradiation (TBI) (12.0 Gy) and cyclophosphamide (100 mg/kg) dose. GvHD prophylaxis included cyclosporine and mycophenolate mofetil. Since mycophenolate mofetil can lead to fatal fibrosing cholestatic hepatitis, the dosing was decreased from three times daily to twice daily. Neutrophil engraftment occurred on day +13 after HSCT and peripheral blood chimerism by variable number tandem repeat was 100% donor. The patient developed sinusoidal obstruction syndrome on day +20 after HSCT with elevated bilirubin of 4.1 mg/dL, weight gain >5%, right upper quadrant tenderness and hepatomegaly. Ultrasound demonstrated enlarged liver (13.7 cm) with normal hepatopetal flow. Defibrotide was given until day +28 when sinusoidal obstruction syndrome resolved. She recovered from her regimen-related toxicities and was discharged on day +36 after HSCT. There was no evidence of GvHD and mycophenolate mofetil was discontinued on day +50 after HSCT.

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Acknowledgements

We would like to acknowledge and thank Lisa Beattie for her clinical support and Shane Cross for his pharmacology expertise. This work has been funded by NIH 5 P30CA02176536, American Association for Cancer Research, St. Baldrick’s Foundation, Assisi Foundation of Memphis, Individual Biomedical Research Award from The Hartwell Foundation and American Lebanese Syrian Associated Charities.

Author contributions

Conception and design: MHD; financial support: MHD and PT; provision of study material or patients: PT, TS and MHD; collection and assembly of data: TS and MHD; data analysis and interpretation: TS, MHD and PT; and manuscript writing: all authors. Final approval of manuscript: all authors.

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Authors and Affiliations

  1. Department of Immunology, St. Jude Children’s Research Hospital, University of Tennessee Health Science Center, College of Medicine, Memphis, TN, USA

    P Thomas

  2. Department of Pathology, St. Jude Children’s Research Hospital, University of Tennessee Health Science Center, College of Medicine, Memphis, TN, USA

    T Santiago

  3. Department of Bone Marrow Transplantation and Cellular Therapy St. Jude Children’s Research Hospital, University of Tennessee Health Science Center, College of Medicine, Memphis, TN, USA

    M H Dallas

  4. Department of Pediatrics, University of Tennessee Health Science Center, College of Medicine, Memphis, TN, USA

    M H Dallas

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  1. P Thomas
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Correspondence to M H Dallas.

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Thomas, P., Santiago, T. & Dallas, M. Treatment of hepatitis C in a pediatric patient using simeprevir and sofosbuvir immediately after an umbilical cord blood transplantation. Bone Marrow Transplant 51, 735–737 (2016). https://doi.org/10.1038/bmt.2015.309

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