Woo M H, Hak L J, Storm M C, Sandlund J T, Ribeiro R C, Rivera G K, Rubnitz J E, Harrison P L, Wang B, Evans W E, Pui C H, Relling M V
Departments of Pharmaceutical Sciences, Hematology-Oncology, and Biostatistics and Epidemiology, St. Jude Children's Research Hospital, and Colleges of Pharmacy and Medicine, University of Tennessee, Memphis, TN 38105, USA.
J Clin Oncol. 2000 Apr;18(7):1525-32. doi: 10.1200/JCO.2000.18.7.1525.
Development of antibodies and hypersensitivity to asparaginase are common and may attenuate asparaginase effect. Our aim was to determine the relationship between antiasparaginase antibodies or hypersensitivity reactions and event-free survival (EFS).
One hundred fifty-four children with acute lymphoblastic leukemia received Escherichia coli asparaginase 10,000 IU/m(2) intramuscularly three times weekly for nine doses during multiagent induction and reinduction phases and for seven monthly doses during continuation treatment. Erwinia asparaginase was used in case of clinical hypersensitivity to E coli but not for subclinical development of antibodies. Plasma antiasparaginase antibody concentrations were measured on day 29 of induction in 152 patients.
Antibodies were detectable in 54 patients (35.5%), of whom 30 (55.6%) exhibited hypersensitivity to asparaginase. Of the 98 patients who had no detectable antibodies, 18 (18.4%) had allergic reactions. Patients with antibodies were more likely to have a reaction than those without antibodies (P <.001). Among the 50 patients who experienced allergic reactions (including two for whom antibodies were not measured), 36 (72.0%) were subsequently given Erwinia asparaginase; seven (19.4%) reacted to this preparation. EFS did not differ among patients who did and did not have antibodies (P =.54), with 4-year EFS (+/- 1 SE) of 83% +/- 6% and 76% +/- 5%, respectively. Similarly, EFS did not differ among patients who did and did not develop allergic reactions (P =.68), with 4-year estimates of 82% +/- 6% and 78% +/- 5%, respectively.
In this setting, in which most patients with allergy were switched to another preparation, there was no adverse prognostic impact of clinical or subclinical allergy to asparaginase.
对门冬酰胺酶产生抗体及超敏反应很常见，且可能减弱门冬酰胺酶的疗效。我们的目的是确定抗门冬酰胺酶抗体或超敏反应与无事件生存期（EFS）之间的关系。
154例急性淋巴细胞白血病患儿在多药诱导和再诱导阶段接受大肠杆菌门冬酰胺酶10000 IU/m²，每周3次肌肉注射，共9剂，在维持治疗阶段每月注射7剂。若对大肠杆菌临床过敏则使用欧文氏菌门冬酰胺酶，但不用于抗体亚临床产生的情况。在152例患者诱导治疗的第29天检测血浆抗门冬酰胺酶抗体浓度。
54例患者（35.5%）可检测到抗体，其中30例（55.6%）对门冬酰胺酶表现出超敏反应。在98例未检测到抗体的患者中，18例（18.4%）有过敏反应。有抗体的患者比无抗体的患者更易发生反应（P<.001）。在50例发生过敏反应的患者中（包括2例未检测抗体的患者），36例（72.0%）随后接受了欧文氏菌门冬酰胺酶治疗；7例（19.4%）对此制剂有反应。有抗体和无抗体的患者EFS无差异（P = 0.54），4年EFS（±1 SE）分别为83%±6%和76%±5%。同样，发生和未发生过敏反应的患者EFS无差异（P = 0.68），4年估计值分别为82%±6%和78%±5%。
在这种情况下，大多数过敏患者换用了另一种制剂，门冬酰胺酶临床或亚临床过敏对预后无不良影响。
