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High angiopoietin-2 and suppression of tumorigenicity-2 levels correlate with onset of sinusoidal obstructive syndrome—implication for the utility of serial biomarker monitoring

Bone Marrow Transplantation volume 52, pages 926–928 (2017)Cite this article

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Hepatic sinusoidal obstructive syndrome (SOS), sometimes known as hepatic veno-occlusive disease (VOD), is a known complication and generally occurs as an acute process following hematopoietic stem cell transplant. SOS is occasionally difficult to diagnose and to differentiate from GvHD. Treatments of SOS are limited to supportive care and defibrotide, a recently FDA-approved medication indicated for SOS with multi-organ failure.1 Although early recognition of SOS may improve outcomes,2 optimal diagnostic and prognostic testing of SOS remains undefined. Here, we report two cases of SOS following haplo-identical stem cell transplantation and their clinical correlations with plasma biomarkers of SOS.

Both patients were enrolled on a clinical protocol approved by our institutional review board (14-H-0180, NCT02226861 and 94-H-0010, NCT00001397) after obtaining informed consent, including the use of samples for research (04-H-0012, NCT00071045) in accordance with the Declaration of Helsinki. Patients received myeloablative conditioning regimens of fludarabine 120 mg/m2 and TBI 1200 cGy. Thereafter the patients received donor lymphocyte infusion (2 × 108 CD3+ cells per kg) on day −6, followed by post-donor lymphocyte infusion cyclophosphamide 120 mg/kg over days −3 and −2. CD34+ selected, peripheral blood progenitor cells were infused on day 0. Sirolimus was initiated on day −1 and ultra-low-dose interleukin 2 (aldesleukin, 100 000 IU/m2) was given SC daily starting day +1 as GvHD prophylaxis.3 Serial plasma samples were collected post transplant and levels of biomarkers (suppression of tumorigenicity-2(ST2), Reg3α, sTNFR1, angiopoietin-2 (ANG2)) were measured using a multiplex microfluidic channel assay (ProteinSimple, San Jose, CA, USA).4

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Acknowledgements

We thank the patients who participated in this study. This research was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute at the National Institutes of Health.

Author contributions

Study concept and design: ATN, AJB, SI; laboratory experiment and data collection: PJ, PA, FB; analysis and interpretation of data: ATN, PJ, SI; pathological review: DEK, drafting of the manuscript: ATN, PM, MB, AJB, SI; clinical care and data collection: ATN, NNS, PM, MB, AJB, SI; obtained funding and study supervision: AJB.

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Authors and Affiliations

  1. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    A T Nunes

  2. Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA

    P Jain, P Anandi, F Chinian, P Muranski, M Battiwalla, A J Barrett & S Ito

  3. Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    D E Kleiner

  4. Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    N N Shah

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  1. A T Nunes
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  2. P Jain
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Correspondence to S Ito.

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Nunes, A., Jain, P., Kleiner, D. et al. High angiopoietin-2 and suppression of tumorigenicity-2 levels correlate with onset of sinusoidal obstructive syndrome—implication for the utility of serial biomarker monitoring. Bone Marrow Transplant 52, 926–928 (2017). https://doi.org/10.1038/bmt.2017.38

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