Bleomycin as an Effective and Curative Adjunct Therapy for Lymphangioma

NCT06943703 | Completed

• 1 other identifier: VUNI.2223.SG04
• Study Type: observational
• Target: 809
• Locations: 1 country
• Sites: 1

Brief Summary

Lymphatic malformations (LM), or lymphangiomas, are common vascular anomalies in children, most often occurring in the head and neck, less commonly in the axilla, abdomen, thorax, groin, and extremities. These benign but locally invasive lesions can cause complications such as respiratory issues, difficulty swallowing, nerve compression, bleeding, and cosmetic disfigurement. Treatment traditionally involves surgical excision, but this approach carries risks such as nerve damage, high recurrence, and poor cosmetic results. In recent years, sclerotherapy, specifically Bleomycin injection, has emerged as a less invasive alternative, offering potential benefits like reduced recurrence and better cosmetic outcomes. Since its introduction in Vietnam in 2016, Bleomycin has been used to treat LM, but comprehensive studies on its safety, efficacy, and long-term outcomes in pediatric patients are lacking. This study aims to fill this gap by evaluating the effectiveness of intralesional Bleomycin injections in children with LM treated at the National Children's Hospital between 2018 and 2022. The study will assess the safety, efficacy, and long-term outcomes of Bleomycin, focusing on lesion size reduction, recurrence rates, and cosmetic and health-related quality of life (QoL) improvements. The retrospective study will involve more than 800 pediatric patients and use tools like the Patient Scar Assessment Questionnaire (PSAQ) and Short Form-36 (SF-36) health survey to evaluate cosmetic outcomes and overall well-being. The research will also compare the effectiveness of Bleomycin alone versus in combination with surgery, examining whether Bleomycin can reduce the need for additional interventions. By offering a comprehensive evaluation of both clinical and patient-reported outcomes, the study aims to establish Bleomycin as a viable, minimally invasive treatment option for pediatric LM, improving both clinical and cosmetic outcomes for these patients. In addition, this study will provide valuable local data on Bleomycin's use in Vietnam, potentially influencing national treatment guidelines. The results will be disseminated in peer-reviewed journals, contributing to global understanding of Bleomycin's role in managing lymphatic malformations in children.

Conditions

Lymphangioma; Lymphatic Malformations

Keywords

Bleomycin; Lymphangioma; Lymphatic malformations; Intralesional Bleomycin injection; Sclerotherapy; Quality of life; Pediatric vascular anomalies; Head and neck; Safety and efficacy; Cosmetic; Non-surgical; Abdominal; Axilla; Thorax

Outcome Measures

Primary Outcomes (7)

• Change in Lesion Size

  The degree of lesion size change will be measured to assess the efficacy of intralesional Bleomycin injection. This will be evaluated through clinical examination and imaging techniques (e.g., ultrasound or MRI) to determine the extent of regression of the lymphangioma.

  Through study completion, an average of 5 years

• Recurrence Rate

  This outcome will track the recurrence rate of lymphangiomas after treatment with Bleomycin. Recurrence is defined as the reappearance or regrowth of the lesion after an initial reduction in size following treatment.

  Through study completion, an average of 5 years

• Adverse Reactions

  The safety of the Bleomycin treatment will be assessed by monitoring adverse reactions, including infection, bleeding, swelling, or allergic reactions at the injection site, as well as any systemic side effects.

  1 week after each injection

• Number of Injections Required for Remission

  The number of Bleomycin injections required to achieve remission (defined as significant size reduction or complete resolution of the lesion) will be recorded. This will help assess the treatment protocol's efficiency and the typical treatment burden for patients.

  Through study completion, an average of 5 years

• Proportion of patients requiring additional interventions

  This outcome will track the proportion of patients requiring additional interventions (e.g., surgical excision or further sclerotherapy sessions) after the initial Bleomycin treatment. The goal is to determine if Bleomycin alone is sufficient to treat the lymphangiomas or if supplementary interventions are necessary.

  Through study completion, an average of 5 years

• PSAQ score - Cosmetic Outcomes and Scar Perception

  Cosmetic outcomes and patient scar perception were evaluated using the Patient Scar Assessment Questionnaire (PSAQ). This validated tool includes multiple subscales assessing appearance, symptoms, consciousness, and satisfaction with appearance. Each subscale is scored on a 4-point Likert scale, with individual item scores ranging from 1 to 4, where lower scores indicate better cosmetic outcomes and greater patient satisfaction. The minimum total score is 18, and the maximum is 72, with lower total scores representing more favorable scar outcomes.

  Through study completion, an average of 5 years

• SF-36 score - Health-Related Quality of Life (QoL)

  Health-related quality of life was assessed using the Short Form-36 Health Survey (SF-36), a validated instrument comprising 36 items across eight domains: physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, and general health perceptions. Scores for each domain range from 0 to 100, with higher scores indicating better health-related quality of life. Both individual domain scores and composite physical and mental component summary scores were analyzed.

  Through study completion, an average of 5 years

Secondary Outcomes (2)

• Follow-Up Time

  Through study completion, an average of 5 years

• Time to Regrowth of Lesion

  Through study completion, an average of 5 years

Study Arms (1)

Pediatric Patients with Lymphangiomas Treated with Intralesional Bleomycin

This cohort consists of pediatric patients under the age of 18, diagnosed with lymphangiomas (lymphatic malformations), treated at the National Children's Hospital between 2018 and 2022. The lymphangiomas in this group are most commonly located in the head and neck, but may also occur, though less frequently, in the axilla, abdomen, thorax, groin, and extremities. The patients included in this cohort were selected based on their diagnosis of lymphangiomas without serious comorbidities that could complicate treatment or outcomes of the sclerotherapy. These patients were managed or observed during the study period, and the cohort represents a diverse age range of children under 18.

Drug: Sclerotherapy with intralesional bleomycin injection

Interventions

Sclerotherapy with intralesional bleomycin injection DRUG

The intervention studied is intralesional Bleomycin injection, which involves the direct injection of Bleomycin, a chemotherapeutic agent, into the lymphangioma lesions. This minimally invasive procedure is aimed at reducing the size of the lymphangioma by disrupting the abnormal growth of lymphatic vessels. The dosage of Bleomycin is tailored based on the patient's body weight, typically ranging from 1 to 3 mg per kg of body weight per injection. The intervention is distinct from other treatments, such as surgical excision or other sclerotherapy agents, as it specifically utilizes Bleomycin's mechanism of action to induce tissue sclerosis and promote lesion regression without the need for invasive surgery. This intervention may require multiple treatment sessions, depending on the size, location of the lymphangioma, and individual's response to therapy, with the goal of achieving long-term effectiveness and improving cosmetic outcomes.

Pediatric Patients with Lymphangiomas Treated with Intralesional Bleomycin

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The population of pediatric patients for this study will consist of children under the age of 18 who have been diagnosed with lymphangiomas (lymphatic malformations). These patients will have a variety of lesion locations, including the head and neck, axilla (armpit), abdomen, thorax (chest), groin, or extremities. The age range will encompass infants, children, and adolescents. They might or might not have received previous treatment with Bleomycin or other interventions for lymphatic malformations. Additionally, they might or might not serious comorbidities such as uncontrolled systemic diseases or immunosuppressive conditions. The cohort will be selected from the patient population at the National Children's Hospital, and participants will be enrolled based on a confirmed diagnosis of lymphangioma from 2018 to 2022.

You may qualify if:

• Age: Pediatric patients under the age of 18 years.
• Diagnosis: Confirmed diagnosis of lymphangioma (lymphatic malformation).
• Location of Lesions: Lymphangiomas located in the head and neck, axilla, abdomen, thorax, groin, or extremities.
• Treatment History: No prior treatment with Bleomycin for lymphangioma.
• Health Status: No serious comorbidities or medical conditions that could interfere with the study or treatment process.
• Informed Consent: Patients (or their legal guardians) provide informed consent to participate in the study.

You may not qualify if:

• Age: Patients over the age of 18 years.
• Pregnancy: Pregnant or breastfeeding patients.
• Other Treatments: Patients who have received prior treatments with Bleomycin for lymphangioma.
• Severe Comorbidities: Presence of serious comorbidities (e.g., uncontrolled cardiovascular disease, active infections) that may interfere with the study or treatment process.
• Allergy: Known allergy or hypersensitivity to Bleomycin or any of its components.
• Active Infections: Patients with active local or systemic infections at the time of enrollment.
• Immunosuppression: Immunocompromised patients (due to illness or medications).

Sponsors & Collaborators

• National Children's Hospital, Vietnam: lead

Study Sites (1)

Department of Surgery, The National Children Hospital, Hanoi

Hanoi, Vietnam

Location

Related Publications (13)

• Porwal PK, Dubey KP, Morey A, Singh H, Pooja S, Bose A. Bleomycin Sclerotherapy in Lymphangiomas of Head and Neck: Prospective Study of 8 Cases. Indian J Otolaryngol Head Neck Surg. 2018 Mar;70(1):145-148. doi: 10.1007/s12070-017-1243-x. Epub 2018 Jan 8.

  PMID: 29456959 BACKGROUND

• Ameh EA, Nmadu PT. Cervical cystic hygroma: pre-, intra-, and post-operative morbidity and mortality in Zaria, Nigeria. Pediatr Surg Int. 2001 Jul;17(5-6):342-3. doi: 10.1007/s003830000558.

  PMID: 11527161 BACKGROUND

• Acevedo JL, Shah RK, Brietzke SE. Nonsurgical therapies for lymphangiomas: a systematic review. Otolaryngol Head Neck Surg. 2008 Apr;138(4):418-24. doi: 10.1016/j.otohns.2007.11.018.

  PMID: 18359347 BACKGROUND

• Bawazir OA, Bawazir R, Bawazir A, Kausar N, Said H. Efficacy and Clinical Outcomes of Bleomycin in the Treatment of Lymphangiomas: A Multicenter Experience. Dermatol Surg. 2021 Jul 1;47(7):948-952. doi: 10.1097/DSS.0000000000002976.

  PMID: 33625132 BACKGROUND

• Yang Y, Sun M, Ma Q, Cheng X, Ao J, Tian L, Wang L, Lei D. Bleomycin A5 sclerotherapy for cervicofacial lymphatic malformations. J Vasc Surg. 2011 Jan;53(1):150-5. doi: 10.1016/j.jvs.2010.07.019. Epub 2010 Sep 16.

  PMID: 20843632 BACKGROUND

• Parashar G, Shankar G, Sahadev R, Santhanakrishnan R. Intralesional Sclerotherapy with Bleomycin in Lymphatic Malformation of Tongue an Institutional Experience and Outcomes. J Indian Assoc Pediatr Surg. 2020 Mar-Apr;25(2):80-84. doi: 10.4103/jiaps.JIAPS_2_19. Epub 2020 Jan 28.

  PMID: 32139985 BACKGROUND

• Durani P, McGrouther DA, Ferguson MW. The Patient Scar Assessment Questionnaire: a reliable and valid patient-reported outcomes measure for linear scars. Plast Reconstr Surg. 2009 May;123(5):1481-1489. doi: 10.1097/PRS.0b013e3181a205de.

  PMID: 19407619 BACKGROUND

• Contopoulos-Ioannidis DG, Karvouni A, Kouri I, Ioannidis JP. Reporting and interpretation of SF-36 outcomes in randomised trials: systematic review. BMJ. 2009 Jan 12;338:a3006. doi: 10.1136/bmj.a3006.

  PMID: 19139138 BACKGROUND

• Ardicli B, Karnak I, Ciftci AO, Tanyel FC, Senocak ME. Sclerotherapy with bleomycin versus surgical excision for extracervical cystic lymphatic malformations in children. Surg Today. 2016 Jan;46(1):97-101. doi: 10.1007/s00595-015-1128-0. Epub 2015 Feb 15.

  PMID: 25682445 BACKGROUND

• Upadhyaya VD, Bhatnagar A, Kumar B, Neyaz Z, Kishore JS, Sthapak E. Is multiple session of intralesional bleomycin mandatory for complete resolution of macrocystic lymphatic malformation? Indian J Plast Surg. 2018 Jan-Apr;51(1):60-65. doi: 10.4103/ijps.IJPS_154_17.

  PMID: 29928081 BACKGROUND

• Baskin D, Tander B, Bankaoglu M. Local bleomycin injection in the treatment of lymphangioma. Eur J Pediatr Surg. 2005 Dec;15(6):383-6. doi: 10.1055/s-2005-872922.

  PMID: 16418953 BACKGROUND

• Wassef M, Blei F, Adams D, Alomari A, Baselga E, Berenstein A, Burrows P, Frieden IJ, Garzon MC, Lopez-Gutierrez JC, Lord DJ, Mitchel S, Powell J, Prendiville J, Vikkula M; ISSVA Board and Scientific Committee. Vascular Anomalies Classification: Recommendations From the International Society for the Study of Vascular Anomalies. Pediatrics. 2015 Jul;136(1):e203-14. doi: 10.1542/peds.2014-3673. Epub 2015 Jun 8.

  PMID: 26055853 BACKGROUND

• Tiwari P, Pandey V, Bera RN, Sharma SP, Chauhan N. Bleomycin sclerotherapy in lymphangiomas of the head and neck region: a prospective study. Int J Oral Maxillofac Surg. 2021 May;50(5):619-626. doi: 10.1016/j.ijom.2020.09.008. Epub 2020 Oct 12.

  PMID: 33059994 BACKGROUND

MeSH Terms

Conditions

Lymphangioma; Lymphatic Abnormalities

Interventions

Sclerotherapy

Condition Hierarchy (Ancestors)

Neoplasm, Lymphatic Tissue; Neoplasms by Histologic Type; Neoplasms; Lymphatic Diseases; Hemic and Lymphatic Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Drug Therapy; Therapeutics

Study Officials

• Quang T Nguyen, M.D.

  Department of Pediatric Surgery, The National Hospital of Pediatrics, Hanoi, Vietnam

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Pediatric surgeon

Study Record Dates

• First Submitted: April 6, 2025
• First Posted: April 24, 2025
• Study Start: January 1, 2018
• Primary Completion: December 31, 2022
• Study Completion: February 4, 2025
• Last Updated: April 24, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

VN (1)