Toxicities in Adults with Acute Lymphoblastic Leukemia (ALL) Treated with Regimens Using Pegasparaginase.
Toxicities in Adults with Acute Lymphoblastic Leukemia (ALL) Treated with Regimens Using Pegasparaginase.
复制标题
使用聚门冬酰胺酶的方案治疗成人急性淋巴细胞白血病 (ALL) 的毒性。
DOI：
10.1182/blood.v112.11.1924.1924
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发表时间：
2008
期刊：
影响因子：
20.3
通讯作者：
A. Bleyer
中科院分区：
文献类型：
--
作者：
M. Rytting;M. Earl;D. Douer;B. Muriera;A. Advani;A. Bleyer
背景：目前针对急性淋巴细胞白血病（ALL）的成人治疗策略是以儿科为基础的治疗方案，使这些患者暴露于多剂量的天冬酰胺酶（ASP）。由于给药方便，长效或聚乙二醇化ASP的暴露尤其突出，因为聚乙二醇化ASP可以静脉注射，比短效形式需要更少的剂量。在此之前，由于20世纪70年代有报道称ASP对成人的毒性高于儿童，因此成人患者很少接受含有ASP的治疗方案。我们报告了三种方案中遇到的毒性，其中包括多剂量聚乙二醇化ASP作为成人ALL患者治疗的一部分。方法：迄今为止，3种方案共纳入了92例患者，年龄在14岁至71岁之间。聚乙二醇化ASP的剂量范围为2000-2500 IU/m2。大约330剂聚乙二醇化ASP已被注射。结果：3 ~ 4级肝毒性最突出；47例（51%）患者出现3-4级转氨酶升高，22例（24%）患者出现3-4级高胆红素血症（表）。30例（33%）患者高血糖为3-4级毒性。5例（5%）患者发生聚乙二醇化ASP 3-4级过敏反应。12例（13%）患者发生血栓形成。值得注意的是，3例（3%）患者在磁共振成像扫描中出现脑白质病，伴有可逆性卒中样症状。大多数肝毒性自行消退，使患者能够继续化疗。所有有中风样症状的病人都已完全康复。结论：成人ALL患者接受包括长效ASP在内的多种化疗可发生相当大的肝毒性和高血糖。其他毒性的发生频率与使用长效ASP治疗的儿科患者相似。这种毒性特征值得密切监测，并从使用聚乙二醇化ASP治疗ALL成人的临床试验中持续收集数据。
Background: The current therapeutic strategy of applying pediatric-based regimens for acute lymphoblastic leukemia (ALL) to adults with ALL exposes these patients to multiple doses of asparaginase (ASP). Exposure to long-acting or pegylated ASP is particularly prominent due to dosing convenience, since pegylated ASP can be administered intravenously and requires fewer doses than shorter-acting forms. Previously, adult patients were much less likely to be treated with ASP-containing regimens due to reports from the 1970s of increased toxicity from ASP in adults compared with children. We report on the toxicities encountered in 3 protocols that include multiple doses of pegylated ASP as part of therapy for ALL in adult patients. Methods: Thus far, the 3 protocols have enrolled 92 patients between the ages of 14 and 71 years. The pegylated ASP dose ranges from 2000–2500 IU/m2. Approximately 330 doses of pegylated ASP have been given. Results: Grade 3–4 hepatic toxicity is the most prominent; grade 3–4 transaminase elevation occurred in 47 (51%) patients, and grade 3–4 hyperbilirubinemia was seen in 22 (24%) patients (Table). Hyperglycemia was grade 3–4 toxicity in 30 (33%) patients. Grade 3–4 allergic reactions to pegylated ASP occurred in 5 (5%) patients. Twelve (13%) patients developed thromboses. Of note, 3 (3%) patients have had leukoencephalopathy on magnetic resonance imaging scans with reversible stroke-like symptoms. The majority of hepatic toxicities resolve spontaneously, allowing patients to continue chemotherapy. All of the patients with stroke-like symptoms have fully recovered. Conclusions: Considerable hepatotoxicity and hyperglycemia occur in adult ALL patients treated with polychemotherapy that includes long-acting ASP. Other toxicities occur with a frequency similar to that seen in pediatric patients treated with a long-acting ASP. This toxicity profile warrants close monitoring and continued data collection from clinical trials that use pegylated ASP in adults with ALL.