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Prepublished online as a Blood First Edition Paper on July 3, 2003; DOI 10.1182/blood-2002-08-2372.

Submitted August 20, 2002
Accepted May 24, 2003
Thioguanine offers no advantage over Mercaptopurine in maintenance treatment of childhood ALL: results of the randomized trial COALL-92
Doerthe O Harms*, Ulrich Goebel, Hans J Spaar, Ulrike B Graubner, Norbert Jorch, Peter Gutjahr, and Gritta E Janka-Schaub
Children's University Hospital, Hamburg, Germany
Children's University Hospital, Duesseldorf, Germany
Children's University Hospital, Munich, Germany
Children's Hospital Prof.Hess, Bremen, Germany
Children's Hospital Gilead, Bielefeld, Germany
Children's University Hospital, Mainz, Germany
* Corresponding author; email: doerthe.harms{at}tele2.ch.
The German co-operative study COALL-92 was designed to examine the clinical effectiveness of thioguanine (TG) versus mercaptopurine (MP) in maintenance treatment of childhood acute lymphoblastic leukemia (ALL) in a randomized multicenter trial. The conversion of TG into thiopurine nucleotides, the cytostatic active metabolite of both thiopurines, is more directly. Furthermore TG has shown to be more cytotoxic in vitro compared to MP. Therefore a higher effectiveness of TG in maintenance treatment was postulated. Of 521 patients enrolled into the protocol, 474 were randomized to receive either MP or TG during maintenance therapy in a daily oral dose. After a median observation time of 6.6 years the probability of event-free survival was 79% ± 3 for the MP group (238 children) and 78% ± 3 in the TG group (236 patients). In spite of TGN levels, exceeding those of the MP group 7 times, treatment with TG did not improve the outcome but was more complicated to handle due to a specific toxicity profile of prolonged myelosuppression with marked thrombocytopenia. Therefore MP should remain the preferred drug for maintenance treatment of ALL, unless other studies demonstrated superiority of TG in larger trials or selected patient groups.

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