Pegylated asparaginase in combination with high‐dose methotrexate for consolidation in adult acute lymphoblastic leukaemia in first remission: a pilot study

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Abstract
Summary. The German Multicentre acute lymphoblastic leukaemia (ALL) study group (GMALL) performed a pilot study using pegylated asparaginase (PEG‐ASP) in combination with high‐dose methotrexate as consolidation therapy in the 05/93 protocol. The aim of the study was an intra‐individual comparison of two different doses of PEG‐ASP in 26 patients, with regard to the depletion of asparagine in serum and toxicity. ‘Pharmacokinetic’ monitoring was performed to evaluate the effect of an intra‐individual dose escalation of PEG‐ASP from 500 to 1000 U/m2 intravenously in successive doses. Serum asparaginase activity was targeted at ≥100 U/l for 1 week and ≥50 U/l for 10 d. The second course of PEG‐ASP was administered to 23 patients. Due to hypersensitivity reactions in five patients, only 18 patients were evaluable for pharmacokinetic monitoring. With respect to the PEG‐ASP activity, an effective depletion of asparagine could be postulated in the majority of patients during 10 d after the first administration. The effect of an intraindividual dose escalation form 500 to 1000 U/m2 was evaluable in 17 of 22 patients. An increment in peak PEG‐ASP activity >70% was observed in 65% of the patients. PEG‐ASP was well tolerated. Despite the long half‐life of PEG‐ASP, neither pancreatic nor central nervous toxicities occurred among the 26 adult patients treated in this pilot study.

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