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• W2590967462 abstract "8539 Background: Although mercaptopurine (MP) is the thiopurine antimetabolite conventionally used in the treatment of childhood acute lymphoblastic leukemia (ALL), thioguanine (TG) is more potent than MP in vitro; and in patients, oral or intravenous TG achieves cytotoxic concentrations in CSF. We therefore performed a pilot study of TG administered orally and by 24 h continuous IV infusion (CIVI), as part of multi-agent chemotherapy, in children with standard risk ALL. Methods: Children with newly diagnosed standard risk ALL (age 1 - 10 yrs, WBC < 50k) were eligible. Treatment was based on the best regimen of the CCG 105 trial, with the addition of CIVI TG (480mg/m2) once during consolidation, twice during each interim maintenance and every 8 weeks during the first year of maintenance, and the substitution of oral TG (60mg/m2/d) for oral MP during maintenance. Red blood cell thioguanine nucleotides (TGNs) concentrations were determined periodically. Results: 58 (31 female) pts, median age 4.3 (range 1.4 - 9.9) yrs, were enrolled. The 8 year event-free survival was 84% (plateau reached at 4 yrs), with an 8 year overall survival of 88% (median potential follow-up 8.9 yrs). There were no CNS relapses and no toxic deaths. Toxicities following CIVI-TG included reversible neutropenia and elevated hepatic transaminases. Six pts experienced reversible veno-occlusive disease (VOD) while receiving oral TG. As the contribution of CIVI-TG to the later development of VOD was not known, the study was amended following the 5th case of VOD to discontinue CIVI TG and change all pts to oral MP. TGN concentrations during oral TG administration averaged 95 ng/8x108 RBC (range 12 -447), greater than observed with oral MP administration. Conclusions: Substituting TG for MP is associated with reversible VOD. However, the lack of CNS relapses in this pilot study suggests that TG may lower the risk of developing CNS leukemia. A subsequent randomized study of oral TG vs. MP was performed by the CCG based, in part, on the results of this trial. No significant financial relationships to disclose." @default.
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• W2590967462 date "2005-06-01" @default.
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• W2590967462 title "Treatment of newly diagnosed children with lower-risk leukemia: A collaborative Children’s Cancer Group (CCG)/NCI pilot trial incorporating 6-thioguanine" @default.
• W2590967462 doi "https://doi.org/10.1200/jco.2005.23.16_suppl.8539" @default.
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