Kloos Robin Q H, Pieters Rob, Escherich Gabriele, van der Sluis Inge M
Pediatric Oncology and Hematology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Pediatr Blood Cancer. 2016 Nov;63(11):1928-34. doi: 10.1002/pbc.26123. Epub 2016 Jul 4.
Asparaginase is an important component of pediatric acute lymphoblastic leukemia (ALL) therapy. Unfortunately, this treatment is hampered by hypersensitivity reactions. In general, allergies - regardless of severity - cause complete inactivation of the drug. However, we report atypical allergic reactions without inactivation of asparaginase, here called allergic-like reactions.
Patients with an allergic-like reaction, who were treated according to the Dutch Childhood Oncology Group ALL-11 or the CoALL 08-09 protocol, were described. The reactions were identified by continual measurement of asparaginase activity levels. Characteristics, including timing of occurrence, symptoms, grade, and the presence of antiasparaginase antibodies, were compared to those of real allergies.
Fourteen allergic-like reactions occurred in nine patients. Five reactions were to PEGasparaginase and nine to Erwinia asparaginase. Allergic-like reactions occurred relatively late after the start of infusion compared to real allergies. Antibodies were absent in all but one patient with an allergic-like reaction, while they were detected in all patients with a real allergy. Symptoms and grade did not differ between the groups. Asparaginase was continued with the same formulation in six patients of whom four finished treatment with adequate activity levels.
In conclusion, allergic-like reactions occur relatively late after the start of infusion and without antibodies. Despite these clinical differences, allergic-like reactions can only be distinguished from real allergies by continually measuring asparaginase activity levels. If clinically tolerated, formulations should not be switched in case of allergic-like reactions. Moreover, failure to recognize these reactions may lead to a less favorable prognosis if asparaginase therapy is terminated unnecessarily.
天冬酰胺酶是小儿急性淋巴细胞白血病（ALL）治疗的重要组成部分。不幸的是，这种治疗受到过敏反应的阻碍。一般来说，过敏反应——无论严重程度如何——都会导致药物完全失活。然而，我们报告了天冬酰胺酶未失活的非典型过敏反应，在此称为类过敏反应。
描述了根据荷兰儿童肿瘤学组ALL - 11或CoALL 08 - 09方案治疗的发生类过敏反应的患者。通过持续测量天冬酰胺酶活性水平来识别这些反应。将包括发生时间、症状、分级以及抗天冬酰胺酶抗体的存在情况等特征与真正过敏反应的特征进行比较。
9名患者发生了14次类过敏反应。5次反应针对聚乙二醇天冬酰胺酶，9次针对欧文氏菌天冬酰胺酶。与真正的过敏反应相比，类过敏反应在输注开始后相对较晚发生。除1名发生类过敏反应的患者外，所有患者均未检测到抗体，而所有真正过敏反应的患者均检测到抗体。两组之间的症状和分级没有差异。6名患者继续使用相同制剂的天冬酰胺酶治疗，其中4名患者以足够的活性水平完成了治疗。
总之，类过敏反应在输注开始后相对较晚发生且无抗体。尽管存在这些临床差异，但只有通过持续测量天冬酰胺酶活性水平才能将类过敏反应与真正的过敏反应区分开来。如果临床耐受，发生类过敏反应时不应更换制剂。此外，如果不必要地终止天冬酰胺酶治疗，未能识别这些反应可能导致预后较差。
