sirolimus (NPC 12G / Hyftor / rapalimus)

Gastrointestinal Blue Rubber Bleb Nevus Syndrome in Children: A Case Series Across Endoscopic, Surgical, and Medical Management.

Vu Hoan Manh HM, Pham Hien Duy HD, Pham My Hoan MH, Dang Trang Thu TT et al.

Blue Rubber Bleb Nevus Syndrome (BRBNS) is a rare venous malformation disorder causing recurrent gastrointestinal bleeding and severe anemia. We report three children illustrating endoscopic, surgical, and medical management. All presented with melena and transfusion-requiring anemia. Case 1 developed gastric perforation after endoscopic band ligation and underwent emergency primary repair with bowel-preserving excision of accessible lesions, followed by recovery. Case 2 had more than 100 gastrointestinal lesions and underwent lesion-directed wedge resections, achieving transfusion independence and hemoglobin normalization at 1 year. Case 3 had idiopathic extrahepatic portal vein obstruction, portal hypertension, and diffuse mesenteric disease that was not safely resectable; sirolimus was initiated, but intermittent bleeding and transfusion dependence persisted. Management should be individualized according to lesion burden, anatomical extent, procedural risk, and feasibility of bowel-preserving treatment. Surgery remains important for complications and resectable disease, whereas systemic therapy may be required for diffuse unresectable involvement.

Treatment of Erdheim-Chester disease from the perspective in 2026.

Adam Zdeněk Z, Štork Martin M, Řehák Zdeněk Z, Boichuk Ivanna I et al.

With the discovery of new drugs, treatment of Erdheim-Chester disease (ECD) is gradually evolving and changing. The text provides an overview of effective drugs available in 2026 for patients with ECD. Treatment options: We consider it appropriate to divide treatment into treatment targeting the inflammatory reaction induced by ECD, and treatment targeting malignant histiocytes. To suppress the inflammatory reaction, high doses of glucocorticoids can be used, but only short-term. For long-term suppression of the inflammatory reaction, anakinra is most commonly used. In rare cases, a similar effect has been reported with canakinumab, as well as with sirolimus and anti-TNF drugs. Anakinra is used both alone and in combination with other drugs. ECD cells, like histiocytosis cells from Langerhans cells, are derived from a monocytic lineage, which similarly to the lymphocytic lineage, is very sensitive to cladribine (2-chloro-2'-deoxyadenosine). This drug is the most effective cytostatic agent for patients with ECD. In several smaller clinical studies, the benefit of treatment with interferon alfa has been described. Thus, interferon alfa, despite its side effects, represents one of the treatment options. In cases of severe ECD and the presence of the BRAFV600E mutation, two drugs are recommended - vemurafenib and dabrafenib. For patients with a severe course without the BRAFV600E mutation, MEK kinase inhibitors trametinib and cobimetinib are recommended. The literature contains conflicting conclusions in studies evaluating the dependence of the effectiveness of these drugs on the detection of mutations in the MAPK signaling pathway. Targeted therapy is associated with numerous side effects, as well as the risk of relapse after its discontinuation. If the administered drugs trigger an inflammatory response, anakinra is again used to suppress it. Treatment of ECD always requires an assessment of the extent of the disease and degree of organ damage in order to choose the appropriate therapy.

High Responsiveness of Head and Neck Kaposiform Hemangioendothelioma Without Kasabach-Merritt Phenomenon to Sirolimus Monotherapy.

Xu Yulang Y, Zhou Jiangyuan J, Lan Yuru Y, Yang Linyu L et al.

Sirolimus is the cornerstone therapy for Kaposiform hemangioendothelioma (KHE). The purpose of this study was to evaluate whether anatomical location independently predicts radiologic response to sirolimus monotherapy in KHE without Kasabach-Merritt phenomenon (KMP). We included 21 patients with head and neck KHE without KMP and 50 matched patients with non-head and neck KHE without KMP, all treated with sirolimus monotherapy in five tertiary referral centers in China. The primary outcome was the 12-month radiologic response rate (defined as ≥ 20% tumor volume reduction on MRI). The Cochran-Mantel-Haenszel test was used to adjust for matching factors, and multivariate logistic regression was performed to identify independent predictors of treatment response. The head and neck group achieved a 100% 12-month radiologic response rate versus 76% in the non-head and neck group (adjusted p = 0.012). A near-complete involution rate was 81% versus 44% (adjusted p = 0.003). Multivariate analysis confirmed that head and neck location was the only independent predictor of both radiologic response (OR = 12.34, 95% CI: 1.45-105.21, p = 0.021) and near-complete involution (OR = 5.87, 95% CI: 1.89-18.23, p = 0.002). No disease progression occurred in head and neck cases, while 4% of non-head and neck lesions progressed. Safety and quality-of-life outcomes were comparable between groups. Anatomical location is a significant independent predictor of sirolimus monotherapy efficacy in KHE without KMP. The exceptional radiologic response rate and favorable safety profile support sirolimus monotherapy as a sufficient first-line therapy for head and neck KHE, providing evidence for location-based precision treatment strategies. ClinicalTrials.gov identifier: NCT04775173. What is known about this subject: Kaposiform hemangioendothelioma (KHE) without Kasabach-Merritt phenomenon (KMP) can cause functional impairments, but sirolimus is used as therapy. Efficacy of sirolimus monotherapy may vary by anatomical location, though evidence is limited. This study aimed to evaluate location-specific responses to address this gap. Head and neck KHE lesions exhibit a prominent response to sirolimus monotherapy, with 100% radiologic response at 12 months, which is an independent predictor of treatment efficacy. Near-complete involution was higher in head and neck cases (81% vs. 44%), with no disease progression. Sirolimus monotherapy is recommended for head and neck KHE without KMP, while non-head and neck lesions may need aggressive approaches.

Sirolimus is effective for paediatric Evans syndrome and secondary autoimmune cytopenias: A retrospective cohort study.

McNeill Maggie M, Cellarius Camilla C, Illamperuma Nethmi N, Zipper Rachelle R et al.