An Update on the Treatment of High-Risk Hemangiomas in Infants

 

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An Update on the Treatment of High-Risk Haemangiomas in Infants

I read the article by Szymik-Kantorowicz et al. entitled “Interferon-alfa in the treatment of high-risk haemangiomas in infants” with interest. The study reported interferon-alfa to be an effective pharmacotherapy for high-risk steroid-resistant infantile haemangiomas, with an overall response rate of 87 % [[9]].

The management of life- or function-threatening haemangiomas represents a therapeutic challenge. The frequency with which this severe subset of haemangiomas occurs is estimated to be between 10 % and 20 % of all infantile haemangiomas. High-risk haemangiomas include those that cause ocular compromise, respiratory distress, congestive heart failure, gastrointestinal bleeding, or extensive ulceration. Because dramatic growth is likely to occur in very young infants, prompt treatment is very often imperative [[2]].

Systemic corticosteroids are a mainstay of haemangioma treatment. Despite their use for nearly 50 years, their precise mechanism of action is not well understood. They probably alter cellular and molecular angiogenic pathways by regulating cytokine expression either directly or indirectly [[5]]. In addition, increased vasoconstriction and hormonal influences have been proposed [[2]]. Generally, oral prednisone or prednisolone is given at a dose of 2 to 3 mg/kg daily as a single morning dose for 1 month. The dosage is then tapered slowly and stopped before 1 year of age [[6]]. The response rate to corticosteroids is variable: one-third of haemangiomas show a dramatic shrinkage, one-third exhibit stabilization of growth, and the remaining one third fails to respond [[3]]. Indications for a second-line drug include failure to response to corticosteroids, contraindications to prolonged systemic corticosteroids, complications of steroid therapy, and the rare instance of parental refusal to use steroids [[6]].

I agree with the authors that interferon-alfa should be considered for life-threatening haemangiomas which do not respond to corticosteroids. However, the potential neurotoxicity of this pleiotropic cytokine with potent antiangiogenic activity requires more emphasis. Barlow et al. [[1]] first reported on the development of spastic diplegia in 5 of 26 children treated with interferon-alfa. Functionally significant diplegia persisted in three infants, and in the remaining two, recovery occurred after interferon was discontinued. In a recent large study, Michaud et al. [[7]] reported that 11 of 441 children treated with interferon for vascular lesions developed irreversible spastic diplegia, and an additional 16 out of 441 children developed a motor development disturbance which improved with cessation of therapy. All affected children were less than 1 year of age at initiation of therapy.

Given the severity of this potential complication, in recent years more experts have recommended vincristine as an alternative treatment for steroid-resistant threatening haemangiomas [[6]]. This plant-derived chemotherapy agent has been reported to be a very effective therapy in a haemangioma setting [[5], [8]]. The usual dosage is 0.05 mg/kg in children weighing less than 10 kg, and 1.5 mg/m² in those heavier than 10 kg, given intravenously on a weekly basis [[2]]. Side effects of vincristine therapy are transient and mild. The major adverse reaction is reversible peripheral neuropathy. Hematological toxicity is usually not seen [[3]].

In conclusion, our treatment armamentarium is still limited for those haemangiomas that require intervention. Possible adverse effects must always be taken into account, and treated children should be followed carefully. Further research into the molecular mechanisms of angiogenesis will offer more targeted therapies with the goal of specific, efficacious and low-toxic treatment of threatening hemangiomas in infancy.

References

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MD, Assoc. Prof. Jelena Roganovic

Division of Hematology and Oncology
Department of Pediatrics
Children's Hospital Rijeka

Istarska 43

HR - 51000 Rijeka

Croatia

Email: jelena.roganovic@ri.htnet.hr