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Blood, 1 March 2002, Vol. 99, No. 5, pp. 1536-1543
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
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
Beate Gleißner,
Nicola Gökbuget,
Claus R. Bartram,
Bart Janssen,
Harald Rieder,
Johannes W. G. Janssen,
Christa Fonatsch,
Axel Heyll,
Dimitris Voliotis,
Joachim Beck,
Thomas Lipp,
Gerd Munzert,
Jürgen Maurer,
Dieter Hoelzer,
Eckhard Thiel, and
the
German Multicenter Trials of Adult Acute Lymphoblastic
Leukemia Study Group
From the Department of Hematology, Oncology, and
Transfusion Medicine, University Hospital Benjamin Franklin, Free
University of Berlin, Germany; Department of Hematology, Internal
Medicine, University of Frankfurt, Germany; Institute of Human
Genetics, University of Heidelberg, Germany; Department of Clinical
Genetics, Philipps University, Marburg, Germany; Institute for Medical
Biology, University of Vienna, Austria; Department of Hematology,
Oncology, and Clinical Immunology, University of Düsseldorf,
Germany; Department of Hematology, University of Köln, Germany;
Department of Hematology, University of Mainz, Germany; Medical
Department I, Hospital München-Schwabing, Germany; Medical
Department III, University of Ulm, Germany.
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/µL versus 11 550/µL; 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.
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