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Severe adverse events during sirolimus “off label” therapy for vascular anomalies
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  • Jochen Rössler,
  • Eulalia Baselga,
  • Victoria Davila,
  • Verónica Celis,
  • Andrea Diociaiuto,
  • May El Hachem,
  • Sandrine Mestre,
  • Dario Häberli,
  • Aram Prokop,
  • Christof Hanke,
  • Wolfgang Loichinger,
  • Isabelle Quere,
  • Iris Baumgartner,
  • Charlotte Niemeyer,
  • Friedrich Kapp
Jochen Rössler
Inselspital University Hospital Bern
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Eulalia Baselga
Hospital Sant Joan de Deu
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Victoria Davila
Hospital Sant Joan de Deu
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Verónica Celis
Hospital Sant Joan de Déu
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Andrea Diociaiuto
Bambino Gesù Children Hospital, IRCCS
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May El Hachem
Bambino Gesù Children Hospital, IRCCS
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Sandrine Mestre
University Hospital of Montpellier, FAVA-MULTI Reference Centre for Lymphedema and lymphatic anomalies, University of Montpellier
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Dario Häberli
Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern
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Aram Prokop
Children’s Hospital
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Christof Hanke
Diakonie Klinikum
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Wolfgang Loichinger
University Hospital of Ulm
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Isabelle Quere
University Hospital of Montpellier, FAVA-MULTI Reference Centre for Lymphedema and lymphatic anomalies, University of Montpellier
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Iris Baumgartner
Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern
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Charlotte Niemeyer
University Medical Center Freiburg
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Friedrich Kapp
University Medical Center Freiburg
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Abstract

Objectives: Clinical studies have shown low toxicity and a favorable safety profile for sirolimus in vascular anomalies. Here, we describe severe adverse events (SAEs) observed during “off-label use”. Methods: We performed a retrospective, multicenter chart review for SAEs during “off-label” sirolimus therapy for vascular anomalies and analyzed these cases by a pre-designed workflow. Results: We identified 17 SAEs in 14 patients diagnosed with generalized lymphatic anomaly (n=4), Gorham-Stout disease (n=2), central conducting lymphatic anomaly (n=1), lymphatic malformation (n=4), tufted angioma (n=1), kaposiform hemangioendothelioma (n=1), and venous malformation in a CLOVES syndrome (n=1). Three patients presented two SAEs. The age at initiation of sirolimus therapy was under the age of 2 years (5x), 2 to 6 years (5x) and older than 12 years (4x). SAEs occurred during the first 3 months of sirolimus therapy (7x), between 3 and 12 months (7x) and after one year of therapy (3x). The most frequent SAE was viral pneumonia (8x) resulting in death due to a metapneumovirus infection in a 3 months old and generalized adenovirus infection in a 28 months old child. Sirolimus blood level at the time of SAEs ranged between 2.7 and 21 ng/L. Five patients were on antibiotic prophylaxis during sirolimus therapy. Conclusions: Most SAEs are observed in the first year of sirolimus therapy; however, SAEs can also occur after a longer treatment period. SAEs are potentially life threatening, especially in early infancy. Presence risk factors, i.e. underlying vascular anomaly or immune status, may contribute to the risk of SAEs.

Peer review status:IN REVISION

18 Jun 2020Assigned to Editor
18 Jun 2020Submission Checks Completed
18 Jun 2020Submitted to Pediatric Blood & Cancer
20 Jun 2020Reviewer(s) Assigned
13 Jul 2020Review(s) Completed, Editorial Evaluation Pending
25 Jul 2020Editorial Decision: Revise Major