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Individualized 6‐mercaptopurine increments in consolidation treatment of childhood acute lymphoblastic leukemia: A NOPHO randomized controlled trial |
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| Authors: | Morten Tulstrup Thomas L Frandsen Jonas Abrahamsson Bendik Lund Kim Vettenranta Olafur Gisli Jonsson Hanne Vibeke Hansen Marquart Birgitte Klug Albertsen Mats Heyman Kjeld Schmiegelow On behalf of the Nordic Society of Paediatric Haematology and Oncology |
| Institution: | 1. Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark;2. Department of Pediatrics, Institution for Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;3. Department of Pediatrics, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway;4. Department of Laboratory Medicine, Faculty of Medicine and Health sciences, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway;5. Department of Paediatrics, University of Tampere, Tampere, Finland;6. Department of Pediatrics, Landspitali University Hospital, Reykjavík, Iceland;7. Department of Clinical Immunology, Section 7631, University Hospital Rigshospitalet, Copenhagen, Denmark;8. Department of Pediatric Oncology, Skejby Hospital, Aarhus, Denmark;9. Department of Pediatrics, Astrid Lindgrens Hospital, Stockholm, Sweden;10. Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark |
| Abstract: | ObjectivesThis randomized controlled trial tested the hypothesis that children with non‐high‐risk acute lymphoblastic leukemia could benefit from individualized 6‐mercaptopurine increments during consolidation therapy (NCT00816049). Primary and secondary end points were end of consolidation minimal residual disease (MRD) positivity and event‐free survival.Methods392 patients were randomized to experimental and 396 to standard therapy. Patients allocated to standard therapy received oral 6‐mercaptopurine (25 mg/m2/day) from days 30 to 85, while the experimental arm received stepwise increments of additional 25 mg/m2/day beginning on days 50 and/or 71 unless dose‐limiting myelosuppression had occurred.ResultsIn the experimental arm, 166 patients (42%) received one dose increment, and 62 (16%) received two. Fifty‐seven of 387 (15%) patients in the experimental arm were MRD positive at end of consolidation vs 77 of 389 (20%) in the control arm (P = .08). Five‐year probability of event‐free survival was 0.89 (95% CI: 0.85‐0.93) in the experimental arm vs 0.93 (0.90‐0.96) in the control arm (P = .13). The median accumulated length of 6‐mercaptopurine treatment interruptions was 7 (IQR 2‐12) in the experimental arm vs 4 (IQR 0‐10) in the control arm (P = .002).ConclusionThis study found no benefit from individualized 6‐mercaptopurine increments compared to standard therapy. |
| Keywords: | 6‐mercaptopurine acute lymphoblastic leukemia children consolidation therapy randomized controlled trial |