Replacing cyclophosphamide/cytarabine/ mercaptopurine with cyclophosphamide/ etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: A report from the COG

Michael J. Burke, Wanda L. Salzer, Meenakshi Devidas, Yunfeng Dai, Lia Gore, Joanne M. Hilden, Eric Larsen, Karen R. Rabin, Patrick A. Zweidler-Mckay, Michael J. Borowitz, Brent Wood, Nyla A. Heerema, Andrew J. Carroll, Naomi Winick, William L. Carroll, Elizabeth A. Raetz, Mignon L. Loh, Stephen P. Hunger

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

With modern chemotherapy, approximately 90% of patients with pediatric acute lymphoblastic leukemia are now cured. However, subsets of patients can be identified who remain at very high risk of relapse with expected 4-year disease-free survival rates <80%; such patients are appropriate candidates for intensive therapeutic strategies designed to improve survival. The AALL1131 trial was designed to determine, in a randomized fashion, whether substitution with cyclophosphamide/etoposide (experimental arm 1) would improve the 4-year disease-free survival of children, adolescents, and young adults with very high-risk B-cell acute lymphoblastic leukemia compared to a modified Berlin-Frankfurt-Münster regimen (control arm). Patients 1-30 years of age with newly diagnosed very high-risk B-cell acute lymphoblastic leukemia were randomized after induction in a 1:2 fashion to the control arm or experimental arm 1 in which they were given cyclophosphamide (440 mg/m2 days 1-5)/ etoposide (100 mg/m2 days 1-5) during part 2 of consolidation and delayed intensification. Prospective interim monitoring rules for efficacy and futility were included where futility would be determined for a one-sided P-value ≥0.7664. The study was stopped for futility as the interim monitoring boundary was crossed [hazard ratio 0.606 (95% confidence interval: 0.297-1.237)] and the very high-risk arm of AALL1131 was closed in February 2017. Using data current as of December 31, 2017, 4-year disease-free survival rates were 85.5±6.8% (control arm) versus 72.3±6.3% (experimental arm 1) (P-value = 0.76). There were no significant differences in grade 3/4 adverse events between the two arms. Substitution of this therapy for very high-risk B-cell acute lymphoblastic leukemia patients on the Children’s Oncology Group AALL1131 trial (NCT02883049) randomized to cyclophosphamide/etoposide during part 2 of consolidation and delayed intensification did not improve disease-free survival.

Original languageEnglish (US)
Pages (from-to)986-992
Number of pages7
JournalHaematologica
Volume104
Issue number5
DOIs
StatePublished - Apr 30 2019

ASJC Scopus subject areas

  • Hematology

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    Burke, M. J., Salzer, W. L., Devidas, M., Dai, Y., Gore, L., Hilden, J. M., Larsen, E., Rabin, K. R., Zweidler-Mckay, P. A., Borowitz, M. J., Wood, B., Heerema, N. A., Carroll, A. J., Winick, N., Carroll, W. L., Raetz, E. A., Loh, M. L., & Hunger, S. P. (2019). Replacing cyclophosphamide/cytarabine/ mercaptopurine with cyclophosphamide/ etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: A report from the COG. Haematologica, 104(5), 986-992. https://doi.org/10.3324/haematol.2018.204545