TY - JOUR
T1 - Individualized 6-mercaptopurine increments in consolidation treatment of childhood acute lymphoblastic leukemia
T2 - A NOPHO randomized controlled trial
AU - Tulstrup, Morten
AU - Frandsen, Thomas L.
AU - Abrahamsson, Jonas
AU - Lund, Bendik
AU - Vettenranta, Kim
AU - Jonsson, Olafur Gisli
AU - Marquart, Hanne Vibeke Hansen
AU - Albertsen, Birgitte Klug
AU - Heyman, Mats
AU - Schmiegelow, Kjeld
AU - On behalf of the Nordic Society of Paediatric Haematology and Oncology (NOPHO)
PY - 2018
Y1 - 2018
N2 - 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/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. 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.
AB - 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/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. 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.
KW - 6-mercaptopurine
KW - acute lymphoblastic leukemia
KW - children
KW - consolidation therapy
KW - randomized controlled trial
U2 - 10.1111/ejh.12979
DO - 10.1111/ejh.12979
M3 - Journal article
C2 - 28983968
AN - SCOPUS:85038569859
SN - 0902-4441
VL - 100
SP - 53
EP - 60
JO - European Journal of Haematology
JF - European Journal of Haematology
IS - 1
ER -