Effects of allopurinol on 6-mercaptopurine metabolism in unselected patients with pediatric acute lymphoblastic leukemia: a prospective phase II study
Jonatan Källström,
Riita Niinimäki,
Johan Fredlund,
Hartmut Vogt,
Laura Korhonen,
Anders Castor,
Josefine Palle,
Arja Harila,
Magnus Borssén,
Jonas Abrahamsson,
Torben Ek
Affiliations
Jonatan Källström
Children’s Cancer Centre, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Pediatrics, Institute for Clinical Sciences, University of Gothenburg
Riita Niinimäki
Department of Pediatrics and Adolescents, Oulu University Hospital
Johan Fredlund
Department of Pediatrics, Halmstad County Hospital
Hartmut Vogt
Department of Pediatrics, Linköping University Hospital
Laura Korhonen
Department of Pediatrics, University of Turku
Anders Castor
Department of Pediatrics, Skåne University Hospital, Lund
Josefine Palle
Department of Woman _s and Children _s Health, Uppsala University
Arja Harila
Department of Woman _s and Children _s Health, Uppsala University
Magnus Borssén
Department of Pediatrics, Norrlands University Hospital, Umeå
Jonas Abrahamsson
Children’s Cancer Centre, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Pediatrics, Institute for Clinical Sciences, University of Gothenburg
Torben Ek
Children’s Cancer Centre, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Pediatrics, Institute for Clinical Sciences, University of Gothenburg
Allopurinol can be used in maintenance therapy (MT) for pediatric acute lymphoblastic leukemia (ALL) to mitigate hepatic toxicity in patients with skewed 6- mercaptopurine metabolism. Allopurinol increases the erythrocyte levels of thioguanine nucleotides (e-TGN), which is the proposed main mediator of the antileukemic effect and decreases methyl mercaptopurine (e-MeMP) levels, associated with hepatotoxicity. We investigated the effects of allopurinol in thiopurine methyltransferase (TPMT) wild-type patients without previous clinical signs of skewed 6MP metabolism. Fifty-one patients from Sweden and Finland were enrolled in this prospective beforeafter trial during ALL MT. Mean e-TGN increased from 280 nmol/mmol Hb after 12 weeks of standard MT to 440 after 12 weeks of MT with addition of allopurinol 50 mg/m2 (p
