Cargando…

Indications and Limitations of Sirolimus in the Treatment of Vascular Anomalies—Insights From a Retrospective Case Series

BACKGROUND: Despite recent developments, the role of sirolimus in the heterogeneous spectrum of vascular anomalies is yet to be defined, in terms of indication, dosage, and therapy duration, recognizing both its potential and limitations. METHODS: We retrospectively analyzed 16 children with vascula...

Descripción completa

Detalles Bibliográficos
Autores principales: Karastaneva, Anna, Gasparella, Paolo, Tschauner, Sebastian, Crazzolara, Roman, Kropshofer, Gabriele, Modl, Manfred, Pfleger, Andreas, Burmas, Ante, Pocivalnik, Mirjam, Ulreich, Raphael, Zenz, Werner, Schwinger, Wolfgang, Beqo, Besiana P., Urban, Christian, Haxhija, Emir Q., Lackner, Herwig, Benesch, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168223/
https://www.ncbi.nlm.nih.gov/pubmed/35676905
http://dx.doi.org/10.3389/fped.2022.857436
_version_ 1784720956142387200
author Karastaneva, Anna
Gasparella, Paolo
Tschauner, Sebastian
Crazzolara, Roman
Kropshofer, Gabriele
Modl, Manfred
Pfleger, Andreas
Burmas, Ante
Pocivalnik, Mirjam
Ulreich, Raphael
Zenz, Werner
Schwinger, Wolfgang
Beqo, Besiana P.
Urban, Christian
Haxhija, Emir Q.
Lackner, Herwig
Benesch, Martin
author_facet Karastaneva, Anna
Gasparella, Paolo
Tschauner, Sebastian
Crazzolara, Roman
Kropshofer, Gabriele
Modl, Manfred
Pfleger, Andreas
Burmas, Ante
Pocivalnik, Mirjam
Ulreich, Raphael
Zenz, Werner
Schwinger, Wolfgang
Beqo, Besiana P.
Urban, Christian
Haxhija, Emir Q.
Lackner, Herwig
Benesch, Martin
author_sort Karastaneva, Anna
collection PubMed
description BACKGROUND: Despite recent developments, the role of sirolimus in the heterogeneous spectrum of vascular anomalies is yet to be defined, in terms of indication, dosage, and therapy duration, recognizing both its potential and limitations. METHODS: We retrospectively analyzed 16 children with vascular anomalies treated with sirolimus in two pediatric centers between 2014 and 2020 [male: n = 7, the median age at diagnosis: 4.6 months (range, 0–281.4)]. In addition, repetitive volumetric analyses of the vascular anomalies were performed when possible (11 cases). RESULTS: Ten patients were diagnosed with vascular malformations and 6 with vascular tumors. The mean therapy duration was 27.2 months (range, 3.5–65). The mean sirolimus level was 8.52 ng/ml (range, 5.38–12.88). All patients except one with central conducting lymphatic anomaly responded to sirolimus, with the most noticeable volume reduction in the first 4–6 months. Additional administration of vincristine was needed in five patients with kaposiform hemangioendothelioma and yielded a response, even in cases, refractory to sirolimus monotherapy. As a single agent, sirolimus led to impressive improvement in a patient with another vascular tumor—advanced epithelioid hemangioendothelioma. Complicated vascular malformations required long-term sirolimus therapy. Side effects of sirolimus included mucositis and laboratory abnormalities. No major infectious episodes were recorded. An infant with COVID-19, diagnosed while on sirolimus therapy, presented with a mild course. CONCLUSION: In the current series, we reported limitations of sirolimus as monotherapy, addressing the need to redefine its indications, and explore combination regimens and multimodal treatment strategies. Tools for objective evaluation of response trends over time could serve as a basis for the establishment of future therapeutic algorithms.
format Online
Article
Text
id pubmed-9168223
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-91682232022-06-07 Indications and Limitations of Sirolimus in the Treatment of Vascular Anomalies—Insights From a Retrospective Case Series Karastaneva, Anna Gasparella, Paolo Tschauner, Sebastian Crazzolara, Roman Kropshofer, Gabriele Modl, Manfred Pfleger, Andreas Burmas, Ante Pocivalnik, Mirjam Ulreich, Raphael Zenz, Werner Schwinger, Wolfgang Beqo, Besiana P. Urban, Christian Haxhija, Emir Q. Lackner, Herwig Benesch, Martin Front Pediatr Pediatrics BACKGROUND: Despite recent developments, the role of sirolimus in the heterogeneous spectrum of vascular anomalies is yet to be defined, in terms of indication, dosage, and therapy duration, recognizing both its potential and limitations. METHODS: We retrospectively analyzed 16 children with vascular anomalies treated with sirolimus in two pediatric centers between 2014 and 2020 [male: n = 7, the median age at diagnosis: 4.6 months (range, 0–281.4)]. In addition, repetitive volumetric analyses of the vascular anomalies were performed when possible (11 cases). RESULTS: Ten patients were diagnosed with vascular malformations and 6 with vascular tumors. The mean therapy duration was 27.2 months (range, 3.5–65). The mean sirolimus level was 8.52 ng/ml (range, 5.38–12.88). All patients except one with central conducting lymphatic anomaly responded to sirolimus, with the most noticeable volume reduction in the first 4–6 months. Additional administration of vincristine was needed in five patients with kaposiform hemangioendothelioma and yielded a response, even in cases, refractory to sirolimus monotherapy. As a single agent, sirolimus led to impressive improvement in a patient with another vascular tumor—advanced epithelioid hemangioendothelioma. Complicated vascular malformations required long-term sirolimus therapy. Side effects of sirolimus included mucositis and laboratory abnormalities. No major infectious episodes were recorded. An infant with COVID-19, diagnosed while on sirolimus therapy, presented with a mild course. CONCLUSION: In the current series, we reported limitations of sirolimus as monotherapy, addressing the need to redefine its indications, and explore combination regimens and multimodal treatment strategies. Tools for objective evaluation of response trends over time could serve as a basis for the establishment of future therapeutic algorithms. Frontiers Media S.A. 2022-05-23 /pmc/articles/PMC9168223/ /pubmed/35676905 http://dx.doi.org/10.3389/fped.2022.857436 Text en Copyright © 2022 Karastaneva, Gasparella, Tschauner, Crazzolara, Kropshofer, Modl, Pfleger, Burmas, Pocivalnik, Ulreich, Zenz, Schwinger, Beqo, Urban, Haxhija, Lackner and Benesch. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pediatrics
Karastaneva, Anna
Gasparella, Paolo
Tschauner, Sebastian
Crazzolara, Roman
Kropshofer, Gabriele
Modl, Manfred
Pfleger, Andreas
Burmas, Ante
Pocivalnik, Mirjam
Ulreich, Raphael
Zenz, Werner
Schwinger, Wolfgang
Beqo, Besiana P.
Urban, Christian
Haxhija, Emir Q.
Lackner, Herwig
Benesch, Martin
Indications and Limitations of Sirolimus in the Treatment of Vascular Anomalies—Insights From a Retrospective Case Series
title Indications and Limitations of Sirolimus in the Treatment of Vascular Anomalies—Insights From a Retrospective Case Series
title_full Indications and Limitations of Sirolimus in the Treatment of Vascular Anomalies—Insights From a Retrospective Case Series
title_fullStr Indications and Limitations of Sirolimus in the Treatment of Vascular Anomalies—Insights From a Retrospective Case Series
title_full_unstemmed Indications and Limitations of Sirolimus in the Treatment of Vascular Anomalies—Insights From a Retrospective Case Series
title_short Indications and Limitations of Sirolimus in the Treatment of Vascular Anomalies—Insights From a Retrospective Case Series
title_sort indications and limitations of sirolimus in the treatment of vascular anomalies—insights from a retrospective case series
topic Pediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168223/
https://www.ncbi.nlm.nih.gov/pubmed/35676905
http://dx.doi.org/10.3389/fped.2022.857436
work_keys_str_mv AT karastanevaanna indicationsandlimitationsofsirolimusinthetreatmentofvascularanomaliesinsightsfromaretrospectivecaseseries
AT gasparellapaolo indicationsandlimitationsofsirolimusinthetreatmentofvascularanomaliesinsightsfromaretrospectivecaseseries
AT tschaunersebastian indicationsandlimitationsofsirolimusinthetreatmentofvascularanomaliesinsightsfromaretrospectivecaseseries
AT crazzolararoman indicationsandlimitationsofsirolimusinthetreatmentofvascularanomaliesinsightsfromaretrospectivecaseseries
AT kropshofergabriele indicationsandlimitationsofsirolimusinthetreatmentofvascularanomaliesinsightsfromaretrospectivecaseseries
AT modlmanfred indicationsandlimitationsofsirolimusinthetreatmentofvascularanomaliesinsightsfromaretrospectivecaseseries
AT pflegerandreas indicationsandlimitationsofsirolimusinthetreatmentofvascularanomaliesinsightsfromaretrospectivecaseseries
AT burmasante indicationsandlimitationsofsirolimusinthetreatmentofvascularanomaliesinsightsfromaretrospectivecaseseries
AT pocivalnikmirjam indicationsandlimitationsofsirolimusinthetreatmentofvascularanomaliesinsightsfromaretrospectivecaseseries
AT ulreichraphael indicationsandlimitationsofsirolimusinthetreatmentofvascularanomaliesinsightsfromaretrospectivecaseseries
AT zenzwerner indicationsandlimitationsofsirolimusinthetreatmentofvascularanomaliesinsightsfromaretrospectivecaseseries
AT schwingerwolfgang indicationsandlimitationsofsirolimusinthetreatmentofvascularanomaliesinsightsfromaretrospectivecaseseries
AT beqobesianap indicationsandlimitationsofsirolimusinthetreatmentofvascularanomaliesinsightsfromaretrospectivecaseseries
AT urbanchristian indicationsandlimitationsofsirolimusinthetreatmentofvascularanomaliesinsightsfromaretrospectivecaseseries
AT haxhijaemirq indicationsandlimitationsofsirolimusinthetreatmentofvascularanomaliesinsightsfromaretrospectivecaseseries
AT lacknerherwig indicationsandlimitationsofsirolimusinthetreatmentofvascularanomaliesinsightsfromaretrospectivecaseseries
AT beneschmartin indicationsandlimitationsofsirolimusinthetreatmentofvascularanomaliesinsightsfromaretrospectivecaseseries