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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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