Hoemberg Marc, Schwenzfeur Ruth, Berthold Frank, Simon Thorsten, Hero Barbara
Department of Pediatric Oncology and Hematology, Children's Hospital, University of Cologne, Cologne, Germany.
Pediatr Blood Cancer. 2022 Feb;69(2):e29374. doi: 10.1002/pbc.29374. Epub 2021 Sep 26.
13-cis-Retinoic acid (13-cisRA) is used as a postconsolidation treatment in patients with high-risk neuroblastoma. Hypercalcemia is a known side effect of retinoids. Frequency, symptoms, treatment, and risk factors for hypercalcemia were analyzed.
Data were retrospectively analyzed for 350 patients registered in the German Neuroblastoma trials NB97 and NB04 who were treated with high-risk protocols-including myeloablative chemotherapy with autologous stem cell transplantation (SCT) or maintenance therapy-and had received 13-cisRA between January 1, 2000 and December 31, 2010.
Hypercalcemia was reported in 78 patients (22.3%), and 37 patients (10.6%) developed Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or 4 hypercalcemia. The calcium levels were 2.5-4.6 mmol/L (median 3.1 mmol/L). Patients with a single kidney were at a higher risk of developing hypercalcemia (p = .001). Regarding postinduction treatment, 69 of 280 patients with SCT (24.6%) and nine of 70 patients without SCT (12.9%) developed hypercalcemia during 13-cisRA treatment (p = .037). Most patients developed hypercalcemia in the first cycle of 13-cisRA, and only in a single cycle. Hypercalcemia symptoms were frequent but moderate. In most patients, treatment with 13-cisRA was continued without dose reduction in subsequent cycles.
In this cohort, grades 3 and 4 hypercalcemia were observed more often than previously reported. A single kidney and pretreatment with myeloablative chemotherapy with stem cell transplantation were identified as potential risk factors for the development of hypercalcemia.
13-顺式维甲酸（13-cisRA）用于高危神经母细胞瘤患者的巩固治疗后。高钙血症是维甲酸类药物已知的副作用。分析了高钙血症的发生率、症状、治疗及危险因素。
对德国神经母细胞瘤试验NB97和NB04中登记的350例患者的数据进行回顾性分析，这些患者接受了高危方案治疗，包括自体干细胞移植（SCT）的清髓性化疗或维持治疗，并于2000年1月1日至2010年12月31日期间接受了13-cisRA治疗。
78例患者（22.3%）报告发生高钙血症，37例患者（10.6%）出现3级或4级高钙血症（按照不良事件通用术语标准[CTCAE]分级）。血钙水平为2.5 - 4.6 mmol/L（中位数3.1 mmol/L）。单肾患者发生高钙血症的风险更高（p = 0.001）。关于诱导治疗后，280例接受SCT的患者中有69例（24.6%），70例未接受SCT的患者中有9例（12.9%）在13-cisRA治疗期间发生高钙血症（p = 0.037）。大多数患者在13-cisRA的第一个周期发生高钙血症，且仅在一个周期内发生。高钙血症症状常见但程度较轻。大多数患者在后续周期中继续使用13-cisRA治疗且未减量。
在该队列中，3级和4级高钙血症的观察发生率高于既往报道。单肾以及干细胞移植清髓性化疗预处理被确定为高钙血症发生的潜在危险因素。
