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Individualized 6‐mercaptopurine increments in consolidation treatment of childhood acute lymphoblastic leukemia: A NOPHO randomized controlled trial
Author(s) -
Tulstrup Morten,
Frandsen Thomas L.,
Abrahamsson Jonas,
Lund Bendik,
Vettenranta Kim,
Jonsson Olafur Gisli,
Marquart Hanne Vibeke Hansen,
Albertsen Birgitte Klug,
Heyman Mats,
Schmiegelow Kjeld
Publication year - 2018
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.12979
Subject(s) - mercaptopurine , medicine , randomized controlled trial , lymphoblastic leukemia , acute lymphocytic leukemia , minimal residual disease , surgery , leukemia
Objectives This 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. Methods 392 patients were randomized to experimental and 396 to standard therapy. Patients allocated to standard therapy received oral 6‐mercaptopurine (25 mg/m 2 /day) from days 30 to 85, while the experimental arm received stepwise increments of additional 25 mg/m 2 /day beginning on days 50 and/or 71 unless dose‐limiting myelosuppression had occurred. Results In 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). Conclusion This study found no benefit from individualized 6‐mercaptopurine increments compared to standard therapy.