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Clinical outcomes of early defibrotide discontinuation: a single-center case series

Bone Marrow Transplantation volume 59, pages 285–287 (2024)Cite this article

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Veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a life-threatening complication of hematopoietic stem cell transplant (HSCT). Defibrotide is FDA approved for the treatment of patients with VOD with renal or hepatic dysfunction after HSCT [1]. The product labeling states that defibrotide should be administered for a minimum of 21 days and up to a maximum of 60 days, until VOD resolution [1]. This recommendation is based on the median time to VOD resolution of 19.5-21.5 days observed in clinical trials supporting defibrotide’s approval [2]. The time to complete response of VOD varies between patients and continuing treatment beyond clinical improvement has the potential for serious defibrotide treatment related adverse events, such as hemorrhage or hypotension, as well as resulting in increased cost associated with drug administration [3, 4]. To our knowledge, there is no post-marketing published literature evaluating discontinuation of defibrotide treatment prior to the 21 day treatment minimum, if complete response is achieved [5]. Further research is needed to determine which patients may have successful treatment outcomes with shorter courses of defibrotide.

Patient 1 was a 23-year-old male diagnosed with acute myelogenous leukemia 5 months prior to receiving a myeloablative matched related peripheral blood stem cell transplant (PBSCT). Preparative regimen consisted of fludarabine (150 mg/m2) and high-dose busulfan (12.8 mg/kg) (FluBu4). GVHD prophylaxis consisted of tacrolimus and methotrexate (FK/MTX). On day + 13, he developed transaminitis, weight gain > 5% from baseline, ascites, and right upper quadrant pain. Abdominal ultrasound with doppler performed on day +13 was consistent with VOD, showing reversal of flow in the left portal vein and anterior branch right portal vein. After these findings, patient was initiated on defibrotide. Liver function test began to improve on day + 18 and diuretics were discontinued by day +21. Repeat ultrasound on day + 21 demonstrated normal venous portal flow. Given the ultrasound results, improvement in renal function, and all other VOD-related symptom improvement, defibrotide was stopped on day +22, totaling 9 days of therapy. Transaminases were still mildly elevated, and total bilirubin (T Bili) was 1.6 mg/dL at time of discontinuation. The patient was discharged from the hospital on day +23 with no further complications from VOD.

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References

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  1. Vanderbilt University Medical Center, Nashville, TN, USA

    Rachael D. Baggett & Katie S. Gatwood

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  1. Rachael D. Baggett
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  2. Katie S. Gatwood
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RB was responsible for reviewing patient charts to identify pertinent information to be included in the case report, writing the original manuscript, editing the manuscript, and manuscript submission. KG identified the patient cases to be included in the case report, provided feedback on the manuscript, and edited the manuscript.

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Correspondence to Rachael D. Baggett.

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Baggett, R.D., Gatwood, K.S. Clinical outcomes of early defibrotide discontinuation: a single-center case series. Bone Marrow Transplant 59, 285–287 (2024). https://doi.org/10.1038/s41409-023-02177-z

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