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

James Nachman, Harland N. Sather, Paul S. Gaynon, John N. Lukens, Lawrence Wolff, Michael E. Trigg

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2222-2230
Number of pages9
JournalJournal of Clinical Oncology
Volume15
Issue number6
StatePublished - Jun 1997
Externally publishedYes

Fingerprint

Induction Chemotherapy
Berlin
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Disease-Free Survival
Neoplasms
Therapeutics
Survival Rate
Radiation
Asparaginase
Drug Therapy
Osteonecrosis
Vincristine
Hypersensitivity
Research Personnel
Escherichia coli

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

@article{c153a745d6e64561adf750241daefa03,
title = "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",
abstract = "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.",
author = "James Nachman and Sather, {Harland N.} and Gaynon, {Paul S.} and Lukens, {John N.} and Lawrence Wolff and Trigg, {Michael E.}",
year = "1997",
month = "6",
language = "English (US)",
volume = "15",
pages = "2222--2230",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "6",

}

TY - JOUR

T1 - 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

T2 - A report from the Children's Cancer Group

AU - Nachman, James

AU - Sather, Harland N.

AU - Gaynon, Paul S.

AU - Lukens, John N.

AU - Wolff, Lawrence

AU - Trigg, Michael E.

PY - 1997/6

Y1 - 1997/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0030915171&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030915171&partnerID=8YFLogxK

M3 - Article

VL - 15

SP - 2222

EP - 2230

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 6

ER -