Pawińska Katarzyna, Balwierz Walentyna, Sztefko Krystyna, Czogała Małgorzata
Klinika Onkologii i Hematologii Dzieciecej, Polsko-Amerykański Instytut Pediatrii Collegium Medicum Uniwersytetu Jagiellońskiego w Krakowie.
Przegl Lek. 2006;63(1):44-6.
L-asparaginase is one of the most important agent used in multidrug chemotherapy regimens in the treatment of malignancies which derive from lymphoid system (acute lymhoblastic leukemias and non-hodgkin lymphoma). L-asparaginase leads to enzymatic cleavage of L-asparagine (amino acid essential for lymphoblasts' growth) to ammonia and L-aspartic acid, what results in depletion of L-asparagine in a serum and cerebrospinal fluid, and finally leads to destruction of lymphoblasts, which lack ability of endogenic L-asparagine production. In the course of L-asparaginase therapy severe side effects could be observed such as: coagulation disturbances, acute pancreatitis, anaphilactic shock and other types of allergic reaction, as well as liver and CNS failure. Monitoring of L-asparaginase activity in serum is recomended in order to optimalize therapy with L-asparaginase and reducing risk of severe side effects. Continuous assessment of L-asparaginase activity during therapy gives also opportunity to detect asymptomatic inactivation of L-ASPA - so called "silent inactivation", which is cused by production of antibodies against xenogenic protein, especcialy in IgG class. This process leads to shortening of half-life of L-ASPA. The paper shows presently available monitoring methods during therapy with L-ASPA, with all their pros and cons.
L-天冬酰胺酶是用于治疗源自淋巴系统的恶性肿瘤(急性淋巴细胞白血病和非霍奇金淋巴瘤)的多药化疗方案中最重要的药物之一。L-天冬酰胺酶导致L-天冬酰胺(成淋巴细胞生长所必需的氨基酸)酶解为氨和L-天冬氨酸,这导致血清和脑脊液中L-天冬酰胺的消耗,最终导致缺乏内源性L-天冬酰胺产生能力的成淋巴细胞的破坏。在L-天冬酰胺酶治疗过程中,可能会观察到严重的副作用,如:凝血障碍、急性胰腺炎、过敏反应和其他类型的过敏反应,以及肝和中枢神经系统衰竭。建议监测血清中L-天冬酰胺酶的活性,以优化L-天冬酰胺酶治疗并降低严重副作用的风险。在治疗期间持续评估L-天冬酰胺酶的活性,也有机会检测到L-ASPA的无症状失活——即所谓的“沉默失活”,这是由针对异种蛋白的抗体产生引起的,尤其是IgG类抗体。这个过程导致L-ASPA半衰期缩短。本文展示了目前L-ASPA治疗期间可用的监测方法,以及它们的优缺点。