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Infectious Complications of Vascular Anomalies Treated with Sirolimus: A Systematic Review
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  • Rachel Kalbfell,
  • Sally J. Cohen-Cutler,
  • Eric Grisham,
  • Christine Bereitschaft,
  • Alexandra Borst,
  • Abby M. Green,
  • Daniel Willis,
  • Lauren Yaeger,
  • Julie Blatt,
  • Bryan Sisk
Rachel Kalbfell
Washington University in St Louis School of Medicine
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Sally J. Cohen-Cutler
The Children's Hospital of Philadelphia
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Eric Grisham
St Louis Children's Hospital
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Christine Bereitschaft
Washington University in St Louis School of Medicine
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Alexandra Borst
The Children's Hospital of Philadelphia
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Abby M. Green
Washington University in St Louis Division of Infectious Diseases
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Daniel Willis
Washington University in St Louis School of Medicine
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Lauren Yaeger
Washington University in St Louis School of Medicine
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Julie Blatt
The University of North Carolina at Chapel Hill Division of Hematology
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Bryan Sisk
Washington University in St Louis School of Medicine

Corresponding Author:siskb@wustl.edu

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Abstract

Background and Objectives: Initially developed as immunosuppressive agents, mTOR inhibitors are currently used widely in the management of vascular malformations and tumors. The incidence of infectious complications in the vascular anomalies (VA) population is not well defined. The goal of this systematic review was to better define the types and severity of reported infectious complications in patients with VAs treated with mTOR inhibition. Methods: This was a systematic review conducted following PRISMA guidelines evaluating all research articles focused on infectious complications in patients with VAs treated with sirolimus or everolimus. Thirty articles including 1181 total patients and 315 infections (in 290 unique patients) were ultimately included. Results: The majority of infections were viral upper respiratory (n=137, 54%), followed by pneumonia (n=52, 20%), and cutaneous infections (n=20, 8%). There were 6 total infection-related fatalities, which all occurred in patients younger than 2 years. Only 1 case of Pneumocystis jirovecii pneumonia (PJP) was reported. This was in an infant with KHE who was also treated with steroids and did not receive PJP prophylaxis. Almost 1/3 (n=95, 32%) of infectious complications were graded 3 to 4 according to CTCAE criteria. Details of patient age, subtype of VA, and timing of infection were lacking from many reports. Conclusions: Most infectious complications reported in patients with VA on mTOR inhibitors were viral respiratory infections and non-severe. Bacteremia, infectious fatalities, and PJP are exceedingly rare. Future studies are needed to clarify the spectrum of infectious risks in VA patients and to provide guidance for infection prevention.
25 Sep 2023Submission Checks Completed
25 Sep 2023Assigned to Editor
25 Sep 2023Submitted to Pediatric Blood & Cancer
25 Sep 2023Review(s) Completed, Editorial Evaluation Pending
25 Sep 2023Reviewer(s) Assigned
09 Oct 2023Editorial Decision: Revise Minor
20 Oct 2023Submission Checks Completed
20 Oct 2023Assigned to Editor
20 Oct 20231st Revision Received
20 Oct 2023Review(s) Completed, Editorial Evaluation Pending
20 Oct 2023Reviewer(s) Assigned
21 Oct 2023Editorial Decision: Accept