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

VL - 100

SP - 53

EP - 60

JO - European Journal of Haematology

JF - European Journal of Haematology

SN - 0902-4441

IS - 1

ER -