Long-term results of five consecutive trials in childhood acute lymphoblastic leukemia performed by the ALL-BFM study group from 1981 to 2000.
Between 1981 and 2000, 6609 children (<18 years of age) were treated in five 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 (EFS) (survival) improved from 65% (77%) in study ALL-BFM 81 to 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 (HR) ALL patients, and eliminated in non- HR non-T-ALL patients, if it was replaced by high-dose and intrathecal (IT) MTX; (2) omission of delayed re-intensification severely impaired outcome of low-risk patients; (3) 6-month-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 significant improvement of outcome; (6) the daunorubicin dose in induction could be safely reduced in low-risk patients and (7) intensification of consolidation/re-intensification treatment led to considerable improvement of outcome in HR patients.
Möricke
A
A
Department of Pediatrics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Zimmermann
M
M
Reiter
A
A
Henze
G
G
Schrauder
A
A
Gadner
H
H
Ludwig
W D
WD
Ritter
J
J
Harbott
J
J
Mann
G
G
Klingebiel
T
T
Zintl
F
F
Niemeyer
C
C
Kremens
B
B
Niggli
F
F
Niethammer
D
D
Welte
K
K
Stanulla
M
M
Odenwald
E
E
Riehm
H
H
Schrappe
M
M
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000628:therapy*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000628:therapy*; D011379:Prognosis; D012307:Risk Factors; D033581:Stem Cell Transplantation; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome