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Blood, Vol. 95 No. 11 (June 1), 2000:
pp. 3310-3322
Improved outcome in childhood acute lymphoblastic leukemia despite
reduced use of anthracyclines and cranial radiotherapy: results of
trial ALL-BFM 90
Martin Schrappe,
Alfred Reiter,
Wolf-Dieter Ludwig,
Jochen Harbott,
Martin Zimmermann,
Wolfgang Hiddemann,
Charlotte Niemeyer,
Günter Henze,
Andreas Feldges,
Felix Zintl,
Bernhard Kornhuber,
Jörg Ritter,
Karl Welte,
Helmut Gadner, and
Hansjörg Riehm for the German-Austrian-Swiss ALL-BFM Study Group
From the Department of Pediatric Hematology and Oncology,
Medizinische Hochschule Hannover, Federal Republic of Germany (FRG);
Department of Hematology, Oncology and Tumor Immunology, Charité,
Campus Berlin-Buch, Humboldt University, Berlin, FRG; Oncogenetic
Laboratory, University Children's Hospital, Gießen, FRG; Department
of Hematology and Oncology, University Göttingen; Germany;
Department of Pediatrics, University Freiburg, FRG; Ostschweizerisches
Kinderspital, St Gallen, Switzerland; Department of Pediatric
Hematology and Oncology, Charité, Humboldt University, Berlin,
FRG; Department of Pediatric Hematology and Oncology, University Jena,
FRG; Department of Pediatric Hematology and Oncology, University
Frankfurt, FRG; Department of Pediatric Hematology and Oncology,
University Münster, FRG; and St Anna Kinderspital, Wien, Austria.
A complete list of the members of the German-Austrian-Swiss ALL-BFM
Study Group appears at the end of this article.
Trial ALL-BFM 90 was designed to improve outcome in patients with
childhood acute lymphoblastic leukemia (ALL) by using a reduced
treatment regimen. Patients were stratified into a standard-risk group (SRG), a medium-risk group (MRG), both defined by adequate early
treatment response; and a high-risk group (HRG), defined by inadequate
response to the cytoreductive prednisone prephase, induction failure,
or Philadelphia-chromosome-positive ALL. Four treatment
modifications were evaluated: dose intensification in induction by a more rapid drug sequence; administration
of L-asparaginase during consolidation therapy in the
MRG (randomized); enforced consolidation by rotational elements in
the HRG; and reduction in the dose of anthracyclines and use of only
12-Gy preventive cranial radiotherapy in the MRG and HRG, with the aim
of avoiding toxicity. Among all 2178 patients ( 18 years of age),
the 6-year event-free survival (EFS) rate (± SE) was
78% ± 1%, with a median observation time of 4.8 years. EFS was
85% ± 2% in the SRG (n = 636) and 82% ± 1% in the
MRG (n = 1299). L-asparaginase did not improve outcome
in the MRG: the event-free interval was 83% ± 2% with
L-asparaginase (n = 528) and 81% ± 2% without it
(n = 557). Because there were more systemic relapses in the HRG
(n = 243), EFS was 34% ± 3%, an outcome inferior to that in
the HRG in a previous trial, ALL-BFM 86, in which EFS was
47% ± 5% (P = .04). The rates of isolated central
nervous system relapse in the MRG and HRG were 0.8% and 1.6%,
respectively; thus, the 12-Gy preventive cranial radiotherapy regimen
apparently provided sufficient central nervous system prophylaxis.
The overall improvement over the results in ALL-BFM 86 (6-year EFS,
72%; P = .001) was based on fewer recurrences among
patients in the MRG with B-cell-precursor ALL, indicating an advantage
of more condensed induction therapy. In multivariate analysis,
inadequate in vivo response emerged as the strongest adverse prognostic variable.
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U. R. Kees, J. Ford, M. Watson, A. Murch, M. Ringner, R. L. Walker, and P. Meltzer
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Should Adolescents With Acute Lymphoblastic Leukemia Be Treated as Old Children or Young Adults? Comparison of the French FRALLE-93 and LALA-94 Trials
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R. Korinthenberg, A. Schneider, and C. Niemeyer
Central Nervous System Prophylaxis With High-Dose Methotrexate Does Not Give Rise to Significant Electroencephalographic Changes in Children With Acute Lymphoblastic Leukemia
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D. Hoelzer, N. Gokbuget, W. Digel, T. Faak, M. Kneba, R. Reutzel, J. Romejko-Jarosinska, J. Zwolinski, and J. Walewski
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Comparison of Escherichia coli-asparaginase with Erwinia-asparaginase in the treatment of childhood lymphoid malignancies: results of a randomized European Organisation for Research and Treatment of Cancer---Children's Leukemia Group phase 3 trial
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M. N. Dworzak, G. Froschl, D. Printz, G. Mann, U. Potschger, N. Muhlegger, G. Fritsch, and H. Gadner
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Delay of the Diagnostic Lumbar Puncture and Intrathecal Chemotherapy in Children With Acute Lymphoblastic Leukemia Who Undergo Routine Corticosteroid Testing: Tokyo Children's Cancer Study Group Study L89-12
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A. J. Strauss, J. T. Su, V. M. K. Dalton, R. D. Gelber, S. E. Sallan, and L. B. Silverman
Bony Morbidity in Children Treated for Acute Lymphoblastic Leukemia
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Value of High-Dose Cytarabine During Interval Therapy of a Berlin-Frankfurt-Munster-Based Protocol in Increased-Risk Children With Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma: Results of the European Organization for Research and Treatment of Cancer 58881 Randomized Phase III Trial
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L. B. Silverman, R. D. Gelber, V. K. Dalton, B. L. Asselin, R. D. Barr, L. A. Clavell, C. A. Hurwitz, A. Moghrabi, Y. Samson, M. A. Schorin, et al.
Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber Consortium Protocol 91-01
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Y. Oki, Y. Kishi, M. Kami, O. Fruchter, M. G. Valsecchi, M. Schrappe, and C.-H. Pui
Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia in Children
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