Rizzari Carmelo, Citterio Marco, Zucchetti Massimo, Conter Valentino, Chiesa Robert, Colombini Antonella, Malguzzi Silvia, Silvestri Daniela, D'Incalci Maurizio
Department of Pediatric Hematology-Oncology, University of Milano-Bicocca, S. Gerardo Hospital, Monza, Italy.
Haematologica. 2006 Jan;91(1):24-31.
Pegylated-asparaginase (PEG-ASP) has been traditionally used as a second-line preparation in children with acute lymphoblastic leukemia (ALL) presenting with clinical allergy to native asparaginase (ASP) products. The main goal of the present study was to investigate the pharmacological effects of the administration of PEG-ASP given as a first-line product in children with ALL.
PEG-ASP serum enzymatic activity and serum and cerebrospinal fluid (CSF) levels of asparagine were investigated in 20 children with newly diagnosed ALL enrolled in the ongoing AIEOP ALL 2000 protocol and treated with PEG-ASP as a first-line ASP preparation. During induction the drug was administered at the dosage of 1,000 U/m2 i.v. on days 12 and 27. During reinduction the drug was administered only once at the same dosage.
Among the 20 patients treated in induction serum PEG-ASP activity equalled or exceeded 100 U/L in 18/18, 11/11 and 15/18 of the samples available on days 22, 25 and 27, respectively, and in 16/16, 12/15 and 5/8 samples available on days 36, 39 and 45, respectively. In the 15 patients treated during reinduction serum PEG-ASP activity > or =100 U/L was observed in 14/15, 11/14, 6/10, and 0/12 samples available on days 11, 15, 18 and 23, respectively, after the administration of the drug. Serum asparagine levels were below the detection limit (< or =0.2 microM) in all patients/samples and at all time points evaluated during induction; during reinduction only one patient had detectable asparagine levels from day 11. CSF asparagine levels were below the detection limit of the method only in a few patients during both induction and reinduction.
PEG-ASP given as a first-line ASP product in the context of an intensive chemotherapy protocol for pediatric ALL allowed adequate plasma enzymatic activity and asparagine depletion during both exposures to the drug. However, CSF asparagine depletion was inadequate.
聚乙二醇化天冬酰胺酶（PEG - ASP）传统上用于对天然天冬酰胺酶（ASP）产品有临床过敏反应的急性淋巴细胞白血病（ALL）患儿的二线治疗。本研究的主要目的是调查在ALL患儿中作为一线产品使用PEG - ASP给药的药理作用。
在20例新诊断的ALL患儿中进行研究，这些患儿参加了正在进行的AIEOP ALL 2000方案，并以PEG - ASP作为一线ASP制剂进行治疗。诱导期在第12天和第27天静脉注射给药，剂量为1000 U/m²。再诱导期仅以相同剂量给药一次。
在诱导期接受治疗的20例患者中，分别在第22天、第25天和第27天可获得的样本中，18/18、11/11和15/18的样本中血清PEG - ASP活性等于或超过100 U/L，在第36天、第39天和第45天可获得的样本中，分别为16/16、12/15和5/8。在再诱导期接受治疗的15例患者中，给药后分别在第11天、第15天、第18天和第23天可获得的样本中，14/15、11/14、6/10和0/12的样本中血清PEG - ASP活性≥100 U/L。诱导期所有患者/样本在所有评估时间点血清天冬酰胺水平均低于检测限（≤0.2 μM）；再诱导期仅1例患者在第11天有可检测到的天冬酰胺水平。在诱导期和再诱导期，仅少数患者脑脊液中天冬酰胺水平低于该方法的检测限。
在小儿ALL强化化疗方案中作为一线ASP产品使用PEG - ASP，在两次用药期间均能使血浆酶活性充足且天冬酰胺耗竭。然而，脑脊液中天冬酰胺耗竭不足。
