Replacing cyclophosphamide, cytarabine, and mercaptopurine chemotherapy with cyclophosphamide plus etoposide during consolidation and delayed intensification may not improve disease-free survival (DFS) in very high-risk patients with pediatric B cell acute lymphoblastic leukemia (B-ALL), according to a study published in Haematologica.

The current standard of care cures approximately 90% of pediatric patients with B-ALL. However, a subset of patients remain at very high risk of relapse, with an expected 4-year DFS rate of less than 80%. Researchers compared the cyclophosphamide plus etoposide regimen with a modified Berlin-Frankfurt-Munster regimen in patients aged 30 years and younger with newly diagnosed, very high-risk B-ALL. Patient enrollment began in February 2012 and the randomization closed in February 2017.

In total, 732 patients were randomly assigned post-induction to receive the modified Berlin-Frankfurt-Munster regimen (242 patients) or 440 mg/m2 cyclophosphamide and 100 mg/m2 etoposide (490 patients) for the first 5 days during part 2 of consolidation and delayed intensification.

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The study was stopped when interim results suggested no benefit. Preliminary data showed that 4-year DFS rates were 85.5% for patients in the modified Berlin-Frankfurt-Munster arm but only 72.3% for patients in the cyclophosphamide plus etoposide arm (P =.76). Additionally, there were no significant differences in grade 3 or 4 adverse events between the 2 treatment arms.

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The authors concluded that future therapeutic studies investigating immunologically and molecularly targeted therapies are warranted, as these therapeutic options may have greater potential for improving outcomes in this patient population compared with further intensification of cytotoxic chemotherapy.


1. Burke MJ, Salzer WL, Devidas M et al. Replacement of cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-ALL: a report from the COG [published online December 13, 2018]. Haematologica. doi: 10.3324/haematol.2018.204545