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Blood, Vol. 92 No. 6 (September 15), 1998:
pp. 1898-1909
Immunophenotypic and Genotypic Features, Clinical
Characteristics, and Treatment Outcome of Adult Pro-B Acute
Lymphoblastic Leukemia: Results of the German Multicenter Trials
GMALL 03/87 and 04/89
Wolf-Dieter Ludwig,
Harald Rieder,
Claus R. Bartram,
Barbara Heinze,
Stefan Schwartz,
Winfried Gassmann,
Helmut Löffler,
Dieter Hossfeld,
Gerhard Heil,
Susanne Handt,
Axel Heyll,
Helmut Diedrich,
Konstanze Fischer,
Adelheid Weiss,
Bernd Völkers,
Ülker Aydemir,
Christa Fonatsch,
Nicola Gökbuget,
Eckhard Thiel, and
Dieter Hoelzer
From the Medizinische Fakultät Charité,
Humboldt-Universität, Robert-Rössle-Klinik, Berlin,
Germany; the Klinikum der Philipps-Universität, Marburg, Germany;
Universitätsklinikum, Heidelberg, Germany; Medizinische
Universitätsklinik, Ulm, Germany; Universitätsklinikum
Benjamin Franklin, Berlin, Germany; Städtisches Krankenhaus, 2. Medizinische Klinik, Kiel, Germany; Universitätskrankenhaus
Eppendorf, Hamburg, Germany; Klinikum der RWTH, II. Med. Klinik,
Aachen, Germany; Universitätsklinik, Düsseldorf, Germany;
Medizinische Hochschule, Hannover, Germany; Klinikum der Stadt
Mannheim, Germany; Universitätsklinikum Frankfurt, Germany;
Biometrisches Zentrum für Therapiestudien, München,
Germany; and Institut für Medizinische Biologie der
Universität Wien, Wien, Austria.
In contrast to childhood acute lymphoblastic leukemia (ALL), the
cell-biological features, clinical characteristics, and treatment outcome of CD10 pro-B ALL have not yet been determined
in larger series of adult patients. Therefore, we studied 57 adult
patients with newly diagnosed pro-B ALL (median age, 30 years) enrolled
in two consecutive German multicenter ALL studies (03/87 and 04/89).
Extensive immunophenotypic characterization of leukemic blasts could be
performed on all patients, whereas adequate cytogenetic data were
available in 33 cases and molecular studies in 18 cases, using reverse
transcription-polymerase chain reaction to detect MLL-AF-4 transcripts.
Twenty-two patients demonstrated a t(4;11)(q21;q23) and/or
MLL-AF-4 rearrangements, and 6 patients had other structural
abnormalities, including a t(9;22)(q34;q11) (N = 2). Nine patients
had a normal karyotype. Patients with 11q23 abnormalities tended to be
younger (median age, 29 years) and were characterized by male
predominance (64%), hyperleukocytosis (median leukocyte count, 168 × 109/L), and a frequent coexpression of CD65s (64%) as
compared with patients with other cytogenetic abnormalities or a normal
karyotype. Twelve of 16 (75%) pro-B ALL patients in study 03/87 and 30 of 41 (73%) in study 04/89 achieved a complete remission (CR). Sixteen of 30 patients in study 04/89 remain in continuous CR (CCR) in contrast
to only 2 of 12 patients in study 03/87. Interestingly, all 7 patients
treated with high-dose cytarabine and mitoxantrone as consolidation in
study 04/89 remain alive and leukemia-free. One patient in study 03/87
and 8 in study 04/89 underwent autologous (N = 2) or allogeneic (N
= 7) bone marrow transplantation (BMT). The median remission duration
was 420 days for patients in study 03/87 and has not yet been reached
in study 04/89. The median survival time of all pro-B ALL patients was
571 days in study 03/87 and 747 days in study 04/89. Among the 22 patients with a t(4;11) and/or MLL-AF-4 rearrangements, 17 achieved a CR and 8 are still in CCR, of whom 4 underwent an allogeneic
BMT. Remission duration and overall survival did not differ
significantly between pro-B ALL patients with 11q23 abnormalities and
those with a normal karyotype or other structural abnormalities. These
data indicate that intensification of postremission treatment may
improve the prognosis of adult pro-B ALL, including patients with a
t(4;11).
© 1998 by The American Society of Hematology.
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