Bajčiová V
Klin Onkol. 2015;28 Suppl 4:4S115-20. doi: 10.14735/amko20154s115.
Malignant melanoma is a rare malignancy in the pediatric population. Etiology is usually unknown. Clinical symptoms are nonspecific, clinical behavior and biology features may differ from those in an adult population. The most important prognostic factor is spread of disease. Surgical resection is treatment of choice for localized melanoma. Advanced and metastatic melanoma is still an incurable disease.
We are presenting an eight-year- old boy with metastatic malignant melanoma of unknown origin based on TP53 mutation (Li Fraumeni syndrome). He underwent surgery and adjuvant chemotherapy (temozolomide as single agent). Complete remission was achieved at the end of treatment. Two years after the end of therapy (and 31 months from diagnosis) he developed metastatic progression to the lungs. He has received immunotherapy with ipilimumab, according to our knowledge as the first child under the age of 12 in Europe. He completed three courses of ipilimumab, with irAE (immune related adverse event) grade III during the first course of anti CTLA 4. Therefore, further doses of ipilimumab were given with corticoids and antihistamines as premedication. Also, asymptomatic thyreoiditis grade II has been confirmed. The best documented treatment response is stable disease. Performance status was excellent. Three years since the first progression, he developed further massive progression to the lungs. Second line immunotherapy with anti-PD 1 monoclonal antibody (pembrolizumab) is currently going on. So far, the overall survival of the patient is 74 months.
The presented case study supports the administration of immunotherapy in children younger than 12 years. Therapeutic effect has led to significant overall survival with tolerable toxicity. The problem remains significantly limited number of pediatric clinical trials using immunotherapy.
恶性黑色素瘤在儿科人群中是一种罕见的恶性肿瘤。病因通常不明。临床症状不具有特异性，其临床行为和生物学特征可能与成人人群不同。最重要的预后因素是疾病的扩散。手术切除是局限性黑色素瘤的首选治疗方法。晚期和转移性黑色素瘤仍然是一种无法治愈的疾病。
我们报告一名8岁男孩，基于TP53突变（李-弗劳梅尼综合征）患有来源不明的转移性恶性黑色素瘤。他接受了手术及辅助化疗（替莫唑胺单药治疗）。治疗结束时实现了完全缓解。治疗结束两年后（诊断后31个月），他出现了肺部转移进展。据我们所知，他接受了伊匹单抗免疫治疗，是欧洲首例12岁以下儿童。他完成了三个疗程的伊匹单抗治疗，在抗CTLA-4的第一个疗程中出现了3级irAE（免疫相关不良事件）。因此，后续剂量的伊匹单抗在使用皮质类固醇和抗组胺药进行预处理的情况下给药。此外，已确诊为无症状2级甲状腺炎。记录最好的治疗反应是疾病稳定。体能状态良好。自首次进展以来三年，他肺部又出现了进一步的广泛进展。目前正在进行抗PD-1单克隆抗体（帕博利珠单抗）的二线免疫治疗。到目前为止，该患者的总生存期为74个月。
本病例研究支持对12岁以下儿童进行免疫治疗。治疗效果使总生存期显著延长，且毒性可耐受。问题仍然是使用免疫治疗的儿科临床试验数量明显有限。
