Role of Sirolimus in Treatment of Microcystic , Mixed Lymphatic and Vascular Malformations

Study Overview
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Brief Summary
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Lympho-vascular malformations result from errors in embryologic vasculogenesis involving capillaries, veins, arteries, lymphatics, or a combination of these. Infantile haemangiomas & Vascular malformations like : Capillary malformations & Venous malformations : they increase in size and never regress on their own. & They are generally present at birth, they enlarge in response to infection, hormonal changes or trauma . Lymphatic malformations can be classified into macrocystic (cyst diameter >1cm), microcystic (cyst diameter <1 cm), or mixed , in macrocystic lymphatic malformations, surgery and sclerotherapy are effective . Surgery of microcystic lymphatic malformations remains challenging due to their infiltrative nature & Sclerotherapy is often impossible. As especially large microcystic and mixed malformations are still a therapeutic challenge, pharmaceutical treatment as sirolimus is used in last years as main line of treatment with great efficacy.

Detailed Description
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Lympho-vascular malformations result from errors in embryologic vasculogenesis involving capillaries, veins, arteries, lymphatics, or a combination of these. Infantile haemangiomas & Vascular malformations like : Capillary malformations & Venous malformations : they increase in size and never regress on their own. & They are generally present at birth, they enlarge in response to infection, hormonal changes or trauma . Lymphatic malformations can be classified into macrocystic (cyst diameter >1cm), microcystic (cyst diameter <1 cm), or mixed , in macrocystic lymphatic malformations, surgery and sclerotherapy are effective . Surgery of microcystic lymphatic malformations remains challenging due to their infiltrative nature & Sclerotherapy is often impossible. As especially large microcystic and mixed malformations are still a therapeutic challenge, pharmaceutical treatment as sirolimus is used in last years as main line of treatment with great efficacy. Sirolimus is a natural macrolide isolated from a bacteria strain of the Streptomyces genus & Streptomyces hygroscopicus . It was initially used as an antibiotic and antifungal agent, subsequent studies have revealed impressive cytostatic, antiproliferative, and immunosuppressive properties . Sirolimus not only prevents the growth of abnormal lymphatics but also induces the partial regression of lesions, without apparent effects on normal lymphatics .

Official Title
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Role of Sirolimus in Treatment of Microcystic , Mixed Lymphatic and Vascular Malformations

Conditions
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Microcystic Lymphatic Malformation, Combined Vascular Malformation, Vascular Malformations

Intervention / Treatment
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* Drug: Sirolimus 1Mg Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: from age 6 months to 12 years , not before 6 months to complete their vaccination program & maturation of hepatic enzymes . Patients diagnosed with microcystic & mixed Lymphatic malformations . After failure of other lines of treatment as regard propranolol , steroid for infantile haemangiomas & Vascular malformations and lymphovascular malformations . After failure of surgical excision & injection of bleomycin of Lympho-vascular malformations Exclusion Criteria: Macrocystic Lymphatic malformations & high flow vascular malformations like arterio-venous malformations . An active infection that requires systemic treatment during the attack . Side effects of the drug as ( history of an allergic reaction to sirolimus or patients who develop severe allergic reaction to drug during treatment , hyperlipidemia , leucopenia , etc… ) Chronic liver or kidney disease or on chronic drug treatment as (steroids, interferon or chemotherapeutic agents) . An immunodeficiency condition such as a human immunodeficiency viral infection or primary immunodeficiency disease. Patients who received drug less than 6 months duration .

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| group A<br>microcystic & mixed lymphatic malformation | Drug: Sirolimus 1Mg Oral Tablet<br>* patients with Microcystic , Mixed Lymphatic and Vascular Malformations will be given sirolimus 1 mg oral tab for 3-6 months with follow up of lesion size by clinical exam & ultrasound & MRI to compare lesion size before & after use of the drug with observation of potential side effects & after exclusion of it before use of the drug<br>|
| group B<br>vascular malformation | Drug: Sirolimus 1Mg Oral Tablet<br>* patients with Microcystic , Mixed Lymphatic and Vascular Malformations will be given sirolimus 1 mg oral tab for 3-6 months with follow up of lesion size by clinical exam & ultrasound & MRI to compare lesion size before & after use of the drug with observation of potential side effects & after exclusion of it before use of the drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in size of the lesion | efficacy of sirolimus in decreasing size of the lesion over time , by clinical exam of size lesion & measurement of size of leesion by ultrasound & MRI | 1 year |