A Case Report of 2 Sirolimus-Related Deaths Among Infants With Kaposiform Hemangioendotheliomas

Ying, Hanru; Qiao, Congzhen; Yang, Xi; Lin, Xiaoxi

doi:10.1542/peds.2016-2919

Cited by 52 publications

(54 citation statements)

References 22 publications

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“…Although sirolimus is clearly efficacious, rare side effects, such as interstitial pneumonitis and Pneumocystis carinii pneumonia, may be life-threatening [125,126]. Currently, the optimal sirolimus dose and prophylactic regimen in patients with KHE has not been established.…”

Section: Sirolimusmentioning

confidence: 99%

Kaposiform hemangioendothelioma: current knowledge and future perspectives

Chen

Yang

et al. 2020

Orphanet J Rare Dis

120

180

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Kaposiform hemangioendothelioma (KHE) is a rare vascular neoplasm with high morbidity and mortality. The initiating mechanism during the pathogenesis of KHE has yet to be discovered. The main pathological features of KHE are abnormal angiogenesis and lymphangiogenesis. KHEs are clinically heterogeneous and may develop into a lifethreatening thrombocytopenia and consumptive coagulopathy, known as the Kasabach-Merritt phenomenon (KMP). The heterogeneity and the highly frequent occurrence of disease-related comorbidities make the management of KHE challenging. Currently, there are no medications approved by the FDA for the treatment of KHE. Multiple treatment regimens have been used with varying success, and new clinical trials are in progress. In severe patients, multiple agents with variable adjuvant therapies are given in sequence or in combination. Recent studies have demonstrated a satisfactory efficacy of sirolimus, an inhibitor of mammalian target of rapamycin, in the treatment of KHE. Novel targeted treatments based on a better understanding of the pathogenesis of KHE are needed to maximize patient outcomes and quality of life. This review summarizes the epidemiology, etiology, pathophysiology, clinical features, diagnosis and treatments of KHE. Recent new concepts and future perspectives for KHE will also be discussed.

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Section: Sirolimusmentioning

confidence: 99%

Kaposiform hemangioendothelioma: current knowledge and future perspectives

Chen

Yang

et al. 2020

Orphanet J Rare Dis

120

180

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“…Infectious complications were reported in 5.5% of patients with oral sirolimus treatment; two cases of fatal pulmonary infection developed in two patients (1 month and 6 months of age) with kaposiform hemangioendothelioma. 24 Prophylaxis with trimethoprimsulfamethoxazole was reported in 29.4% of patients. Infectious complications were reported in 2.5% of patients under antibiotic prophylaxis compared with 5.2% of patients without prophylaxis.…”

Section: Safetymentioning

confidence: 99%

Efficacy and safety of sirolimus in the treatment of vascular anomalies: A systematic review

Freixo

Ferreira

Martins

et al. 2020

Journal of Vascular Surgery

142

115

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Objective: The management of vascular anomalies is complex and requires a multidisciplinary team with a combination of medical, surgical, and intervention treatments. Medical treatment is limited and has conflicting results. Off-label use of mammalian target of rapamycin inhibitors shows promising results. The objective of this study was to systematically evaluate the literature published about the efficacy and safety of sirolimus in the treatment of vascular anomalies. Methods: A systematic review of the published literature was conducted using the PubMed database and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: There were 73 articles included: 2 randomized controlled studies, 2 nonrandomized prospective studies, and 69 retrospective case reports and case series. In total, 373 patients were included. Sirolimus was administered topically to 56 patients and orally to 317 patients. Sirolimus was highly effective in the treatment of vascular tumors associated with Kasabach-Merritt phenomenon (95.5% of the patients clinically improved and 93% had normalization of coagulopathy), venous malformations (size reduction was observed in 88.9% of patients), and lymphatic malformations (clinical improvement in 94.9% of patients). Topical sirolimus results were conflicting. Arteriovenous malformations were not improved by sirolimus. Conclusions: Low-level evidence suggests that sirolimus can improve the prognosis of vascular anomalies, most notably vascular tumors associated with life-threatening coagulopathy and venous and lymphatic malformations. Further research is needed to establish the benefits of sirolimus in the management of vascular anomalies.

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“…6,9,10 Currently, sirolimus alone or combined with a short course of oral corticosteroids appears to be the best therapeutic option. [11][12][13][14][15][16][17][18] The optimal sirolimus dose in patients with KMF has not been established, but serum levels should be maintained between 5 and 15 ng/mL. 5,11,15 Low-dose sirolimus, using levels of 2-3 ng/mL, is associated with low toxicity.…”

Section: Low Dose Sirolimus Treatment For Refractory Tufted Angioma Amentioning

confidence: 99%

“…A 2013 consensus recommended steroids associated with vincristine for KMP . Currently, sirolimus alone or combined with a short course of oral corticosteroids appears to be the best therapeutic option . The optimal sirolimus dose in patients with KMF has not been established, but serum levels should be maintained between 5 and 15 ng/mL.…”

mentioning

confidence: 99%