Leading prognostic relevance of the BCR-ABL translocation in adult acute B-lineage lymphoblastic leukemia: a prospective study of the German Multicenter Trial Group and confirmed polymerase chain reaction analysis.
The BCR-ABL fusion, the molecular equivalent of the Philadelphia translocation, gains importance for treatment stratification in adult acute lymphoblastic leukemia (ALL). In this prospective study, samples from 478 patients with CD10(+) B-cell precursor ALL (c-ALL and pre-B ALL) underwent BCR-ABL reverse transcription-polymerase chain reaction (RT-PCR) analysis with double testing of positive samples. Patients were stratified according to the PCR result and treated in 2 German Multicenter Trials of Adult ALL. The outcome was followed and the prognostic impact of BCR-ABL was compared to clinical risk features. Of the 478 samples, 432 had an evaluable BCR-ABL result. Thirty-seven percent of the c-ALL and pre-B ALL patients were BCR-ABL(+) (p190, 77%; p210, 20%; simultaneous p190/p210, 3%). BCR-ABL positivity was associated with the high-risk features of older age (45 years versus 30 years median age; P =.0001) and higher white blood cell counts (23 500/microL versus 11 550/microL; P =.0001). Univariate and multivariate analyses revealed BCR-ABL as the leading factor for a poor prognosis (P =.0001) in comparison to clinical risk criteria. Irrespective of the breakpoint, presence of any BCR-ABL transcript predicted a lower chance of initial treatment response (68.4% versus 84.6%; P =.001) and a lower probability of disease-free survival at 3 years (0.13 versus 0.47; P =.0001). This bad outcome was not influenced by postinduction high-dose treatment stratifications. The results show a high prevalence of BCR-ABL fusion transcripts with predominance of p190. BCR-ABL RT-PCR is confirmed as a sensitive, rapid method to diagnose t(9;22), and p190 and p210 are unequivocally demonstrated as the most important predictors of poor long-term survival despite intensified chemotherapy.
Gleissner
Beate
B
Department of Hematology, Oncology, and Transfusion Medicine, University Hospital Benjamin Franklin, Free University of Berlin, Germany. gleisner@zedat.fu-berlin.de
Gökbuget
Nicola
N
Bartram
Claus R
CR
Janssen
Bart
B
Rieder
Harald
H
Janssen
Johannes W G
JW
Fonatsch
Christa
C
Heyll
Axel
A
Voliotis
Dimitris
D
Beck
Joachim
J
Lipp
Thomas
T
Munzert
Gerd
G
Maurer
Jürgen
J
Hoelzer
Dieter
D
Thiel
Eckhard
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D002051:Burkitt Lymphoma / Q000235:genetics / Q000401:mortality / Q000473:pathology; D020732:Cytogenetic Analysis; D017931:DNA Primers; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000401:mortality / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis; D015996:Survival Rate; D014178:Translocation, Genetic / Q000235:genetics*; D016896:Treatment Outcome
D017931:DNA Primers; D012333:RNA, Messenger; D016044:Fusion Proteins, bcr-abl