Risk-adjusted therapy of acute lymphoblastic leukemia can decrease treatment burden and improve survival: treatment results of 2169 unselected pediatric and adolescent patients enrolled in the trial ALL-BFM 95.
The trial ALL-BFM 95 for treatment of childhood acute lymphoblastic leukemia was designed to reduce acute and long-term toxicity in selected patient groups with favorable prognosis and to improve outcome in poor-risk groups by treatment intensification. These aims were pursued through a stratification strategy using white blood cell count, age, immunophenotype, treatment response, and unfavorable genetic aberrations providing an excellent discrimination of risk groups. Estimated 6-year event-free survival (6y-pEFS) for all 2169 patients was 79.6% (+/- 0.9%). The large standard-risk (SR) group (35% of patients) achieved an excellent 6y-EFS of 89.5% (+/- 1.1%) despite significant reduction of anthracyclines. In the medium-risk (MR) group (53% of patients), 6y-pEFS was 79.7% (+/- 1.2%); no improvement was accomplished by the randomized use of additional intermediate-dose cytarabine after consolidation. Omission of preventive cranial irradiation in non-T-ALL MR patients was possible without significant reduction of EFS, although the incidence of central nervous system relapses increased. In the high-risk (HR) group (12% of patients), intensification of consolidation/reinduction treatment led to considerable improvement over the previous ALL-BFM trials yielding a 6y-pEFS of 49.2% (+/- 3.2%). Compared without previous trial ALL-BFM 90, consistently favorable results in non-HR patients were achieved with significant treatment reduction in the majority of these patients.
Möricke
Anja
A
Department of Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Reiter
Alfred
A
Zimmermann
Martin
M
Gadner
Helmut
H
Stanulla
Martin
M
Dördelmann
Michael
M
Löning
Lutz
L
Beier
Rita
R
Ludwig
Wolf-Dieter
WD
Ratei
Richard
R
Harbott
Jochen
J
Boos
Joachim
J
Mann
Georg
G
Niggli
Felix
F
Feldges
Andreas
A
Henze
Günter
G
Welte
Karl
K
Beck
Jörn-Dirk
JD
Klingebiel
Thomas
T
Niemeyer
Charlotte
C
Zintl
Felix
F
Bode
Udo
U
Urban
Christian
C
Wehinger
Helmut
H
Niethammer
Dietrich
D
Riehm
Hansjörg
H
Schrappe
Martin
M
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016543:Central Nervous System Neoplasms / Q000517:prevention & control; D002648:Child; D002675:Child, Preschool; D016371:Cranial Irradiation; D003561:Cytarabine / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018570:Risk Assessment; D055502:Secondary Prevention; D016019:Survival Analysis
D003561:Cytarabine