Abstract

This case reports concomitant use of enzyme and substrate reduction therapy to improve chemotherapy adherence in a pediatric patient diagnosed with Ewing sarcoma (ES) and type 1 Gaucher disease (GD). The 17-year-old female presented with 5 months of right knee pain with associated mass on exam. She was diagnosed with ES with pulmonary metastasis. The patient was treated with 17 alternating cycles of vincristine-doxorubicin-cyclophosphamide and ifosfamide and etoposide chemotherapy followed by tumor resection and radiation per standard protocol. As part of her staging work-up, bone marrow biopsy was performed, significant for Gaucher cells. After the second cycle of chemotherapy the patient began to experience severe delays averaging 30 days between cycles compared to 17.29 days observed in Children’s Oncology Group data. Given her bone marrow biopsy findings and chemotherapy delays GD screening was obtained and the patient was diagnosed with GD following genetic confirmation. Due to delays in chemotherapy decreasing chance of remission, the patient was referred to Genetics for aggressive management with imiglucerase and eliglustat. After initiation of therapy the period between chemotherapy cycles decreased to 23 days on average, with a 21% increase in platelet count during therapy. The patient was able to complete ES therapy achieving remission. GD is associated with an increased risk of malignancy, as seen in our patient with ES. GD patients experience prolonged hematologic cytopenia during cancer treatment. Combining Enzyme and Substrate Reduction Therapies should be investigated as an option to improve chemotherapy adherence in GD patients.

摘要

该病例报告了同时使用酶和底物减少疗法来改善诊断为尤文肉瘤 (ES) 和 1 型戈谢病 (GD) 的儿科患者的化疗依从性。这位 17 岁的女性因右膝疼痛 5 个月就诊，检查时伴有肿块。她被诊断出患有 ES 并伴有肺转移。患者接受了 17 个交替循环的长春新碱-多柔比星-环磷酰胺和异环磷酰胺和依托泊苷化疗，然后按照标准方案进行肿瘤切除和放疗。作为分期检查的一部分，进行了骨髓活检，这对戈谢细胞具有重要意义。在第二个化疗周期后，患者开始经历严重的延迟，周期之间平均延迟 30 天，而儿童肿瘤组数据中观察到的延迟为 17.29 天。鉴于她的骨髓活检结果和化疗延迟，获得了 GD 筛查，并且在基因确认后患者被诊断为 GD。由于化疗的延迟降低了缓解的机会，患者被转诊至遗传科以使用伊米苷酶和 eliglustat 进行积极治疗。开始治疗后，化疗周期之间的时间平均减少到 23 天，治疗期间血小板计数增加了 21%。患者能够完成 ES 治疗，达到缓解。正如我们的 ES 患者所见，GD 与恶性肿瘤风险增加有关。GD 患者在癌症治疗期间会经历长时间的血液学血细胞减少。应研究结合酶和底物减少疗法作为改善 GD 患者化疗依从性的一种选择。