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Klin Padiatr 2013; 225(S 01): S62-S72
DOI: 10.1055/s-0033-1337966
Zum 80. Geburtstag von Prof. Riehm
© Georg Thieme Verlag KG Stuttgart · New York

Key Treatment Questions in Childhood Acute Lymphoblastic Leukemia: Results in 5 Consecutive Trials Performed by the ALL-BFM Study Group From 1981 to 2000

Kernfragen der Behandlung von akuten lymphoblastischen Leukämien im Kindesalter: Ergebnisse aus 5 konsekutiven Studien der ALL-BFM-Studiengruppe von 1981 bis 2000
M. Schrappe
1   Department of Pediatrics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany
,
A. Möricke
1   Department of Pediatrics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany
,
A. Reiter
2   Department of Pediatric Hematology and Oncology, University Children’s Hospital, Giessen, Germany
,
G. Henze
3   Department of Pediatric Hematology and Oncology, Charité, Humboldt University, Berlin, Germany
,
K. Welte
4   Department of Pediatric Hematology and Oncology, Medizinische ­Hochschule, Hannover, Germany
,
H. Gadner
5   Department of Pediatrics, St. Anna Kinderspital, Vienna, Austria
,
W.-D. Ludwig
6   Department. of Hematology, Oncology, and Tumor Immunology, Robert-Rössle-Clinic, HELIOS Medical Center Berlin-Buch, Germany
,
J. Ritter
7   Department of Pediatric Hematology and Oncology, University Children’s Hospital, Münster, Germany
,
J. Harbott
8   Oncogenetic Laboratory, University Children’s Hospital, Giessen, Germany
,
G. Mann
5   Department of Pediatrics, St. Anna Kinderspital, Vienna, Austria
,
T. Klingebiel
9   Department of Pediatric Hematology and Oncology, University Children’s Hospital, Frankfurt, Germany
,
B. Gruhn
10   Department of Pediatric Hematology and Oncology, University Children’s Hospital, Jena, Germany
,
C. Niemeyer
11   Department of Pediatric Hematology and Oncology, University Children’s Hospital, Freiburg, Germany
,
B. Kremens
12   Department of Pediatric Hematology and Oncology, University Children’s Hospital, Essen, Germany
,
F. Niggli
13   Department of Pediatric Hematology and Oncology, University Children’s Hospital, Zürich, Switzerland
,
K.-M. Debatin
14   Department of Pediatric Hematology and Oncology, University Children’s Hospital, Ulm, Germany
,
R. Ratei
6   Department. of Hematology, Oncology, and Tumor Immunology, Robert-Rössle-Clinic, HELIOS Medical Center Berlin-Buch, Germany
,
M. Stanulla
1   Department of Pediatrics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany
,
R. Beier
4   Department of Pediatric Hematology and Oncology, Medizinische ­Hochschule, Hannover, Germany
,
G. Cario
1   Department of Pediatrics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany
,
A. Schrauder
1   Department of Pediatrics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany
,
M. Zimmermann
4   Department of Pediatric Hematology and Oncology, Medizinische ­Hochschule, Hannover, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
22 May 2013 (online)

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Abstract

Between 1981 and 2000, 6 609 children (<18 years of age) were treated in 5 consecutive trials of the Berlin-Frankfurt-Münster (BFM) study group for childhood acute lymphoblastic leukemia (ALL). Patients were treated in up to 82 centers in Germany, Austria, and Switzerland. Probability of 10-year event-free survival (survival) improved from 65% (77%) in study ALL-BFM 81–78% (85%) in ALL-BFM 95. In parallel to relapse reduction, major efforts focused on reducing acute and late toxicity through advanced risk adaptation of treatment. The major findings derived from these ALL-BFM trials were as follows: 1) preventive cranial radiotherapy could be safely reduced to 12 Gy in T-ALL and high-risk ALL patients and eliminated in non-high-risk non-T-ALL patients, if it was replaced by high-dose and intrathecal methotrexate; 2) omission of delayed reintensification severely impaired outcome of low-risk patients; 3) 6 months less maintenance therapy caused an increase in systemic relapses; 4) slow response to an initial 7-day prednisone window was identified as adverse prognostic factor; 5) condensed induction therapy resulted in a significant improvement of outcome; 6) the daunorubicin dose in induction could be safely reduced in low-risk patients; 7) intensification of consolidation/reintensification treatment led to considerable improvement of outcome in high-risk patients.

Zusammenfassung

In den Jahren von 1981–2000 wurden 6 609 Kinder mit ALL unter 18 Jahren in 5 aufeinander folgenden klinischen Studien der Berlin-Frankfurt-Münster (BFM) Gruppe in bis zu 82 Kliniken in Deutschland, Österreich und der Schweiz behandelt. Die 10 Jahres-Wahrscheinlichkeit des ereignisfreien Überlebens (bzw. Gesamtüberlebens) verbesserte sich von 65% (77%) in Studie ALL-BFM 81 auf 78% (85%) in Studie ALL-BFM 95. Neben der Reduktion der Rezidive fokussier­ten die Studien durch einen risikoadaptierten Ansatz vor allem auf eine Senkung der akuten und späten Toxizität. Die wichtigsten Ergebnisse dieser Studien waren folgende: 1) Die präventive Schädelbestrahlung konnte bei T-ALL und Hochrisiko-ALL in der Dosis auf 12 Gy reduziert werden und bei allen anderen Patienten sogar eliminiert werden; 2) die Reinduktionstherapie ist selbst bei Niedrigrisiko ALL unverzichtbar; 3) eine um 6 Monate verkürzte Erhaltungstherapie führt zu einem Anstieg von systemischen Re­zidiven; 4) das verzögerte Ansprechen auf eine 7-tägige Prednisonvorphase ist ein ungünstiger Prognosefaktor; 5) eine „kondensierte“, also dosisintensivierte Induktionstherapie führt zu einem signifikant besseren Therapieergebnis; 6) die Daunorubicin Dosis konnte bei Niedrigrisiko Patienten sicher gesenkt werden; 7) mit einer Intensivierung der Konsolidierungselemente ließ sich bei Hochrisikopatienten ein erheblich besseres Therapieergebnis erreichen.

Key words

acute lymphoblastic ­leukemia - ALL - long-term follow-up - prognostic factors

Schlüsselwörter

akute lymphoblastische Leukämie - ALL - Prognosefaktoren - Langzeitergebnisse
 

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