Journal of Clinical Oncology, Vol 15, 2222-2230, Copyright © 1997 by American Society of Clinical Oncology
Augmented Berlin-Frankfurt-Munster therapy abrogates the adverse prognostic significance of slow early response to induction chemotherapy for children and adolescents with acute lymphoblastic leukemia and unfavorable presenting features: a report from the Children's Cancer Group
J Nachman, HN Sather, PS Gaynon, JN Lukens, L Wolff and ME Trigg
University of Chicago, IL, USA.
PURPOSE: Compared with previous Children's Cancer Group (CCG) acute
lymphoblastic leukemia (ALL) trials, therapy based on the Berlin-
Frankfurt-Munster (BFM) 76 trial has effected an improvement in event- free
survival (EFS). In an attempt to improve EFS further, CCG investigators
formulated an augmented BFM (A-BFM) regimen that provides prolonged,
intensified postinduction chemotherapy relative to the CCG- modified BFM
regimen. PATIENTS AND METHODS: We tested A-BFM in 101 patients with ALL and
unfavorable presenting features that showed slow early response (SER) to
induction therapy who attained remission on day 28. Their outcome was
compared with that of 251 concurrent patients with unfavorable presenting
features, a rapid early response to therapy (RER), and remission by day 28,
treated with CCG-BFM with or without cranial radiation (CRT). RESULTS: The
4-year EFS rate from the end of induction for SER patients treated with
A-BFM was 70.8% +/- 4.6%. Seventeen patients remain in continuous remission
beyond 5 years. Vincristine (VCR) neurotoxicity developed in 50% of
patients, but was rarely debilitating. Allergies to Escherichia coli
L-asparaginase (L- ASP) occurred in 35% of patients. Avascular necrosis of
bone (AVN) developed in 9% of patients. In comparison, a concurrent RER
group treated with standard BFM +/- CRT had a 4-year EFS rate of 73.1% +/-
4.6%. CONCLUSION: The toxicity of A-BFM is significant, but acceptable.
Compared with historical control SER patients treated with CCG-modified
BFM, A-BFM therapy appears to produce a significant improvement in EFS.
This is the first study to show that intensive chemotherapy, as given in
the A-BFM regimen, can abrogate the adverse prognostic significance of SER.
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