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Blood, Vol. 94 No. 10 (November 15), 1999:
pp. 3294-3306
Improved Treatment Results in Childhood B-Cell Neoplasms With Tailored
Intensification of Therapy: A Report of the
Berlin-Frankfurt-Münster Group Trial NHL-BFM 90
Alfred Reiter,
Martin Schrappe,
Markus Tiemann,
Wolf-Dieter Ludwig,
Elif Yakisan,
Martin Zimmermann,
Georg Mann,
Andreas Chott,
Wolfram Ebell,
Thomas Klingebiel,
Norbert Graf,
Bernhard Kremens,
Stefan Müller-Weihrich,
Hans-Jürgen Plüss,
Felix Zintl,
Günter Henze, and
Hansjörg Riehm
From the Department of Pediatric Hematology and Oncology,
Medizinische Hochschule, Hannover, Germany; the Lymphnode Registry of
The Society of German Pathologists, Institute of Hematopathology,
Christian-Albrechts-Universität, Kiel, Germany; the Department of
Hematology, Oncology and Tumor Immunology, Charité, Humboldt
University Berlin, Berlin, Germany; the St. Anna Kinderspital, Vienna,
Austria; the Department of Pathology, University of Vienna, Vienna,
Austria; the Department of Pediatric Hematology and Oncology,
Charité, Humboldt University, Berlin, Germany; the Department of
Pediatrics, University of Tübingen, Tübingen, Germany; the
Department of Pediatrics, University of Saarland, Homburg, Germany; the
Department of Pediatric Hematology and Oncology, University of Essen,
Essen, Germany; the Department of Pediatrics, Technical University,
München, Germany; the Department of Pediatrics, University of
Zürich, Zürich, Switzerland; and the Department of
Pediatrics, Friedrich Schiller University, Jena, Germany.
In study NHL-BFM 90, we investigated whether the serum lactate
dehydrogenase (LDH) concentration and early response are useful markers
for stratification of therapy for childhood B-cell neoplasms in
addition to stage, if the outcome of patients with abdominal stage III
and LDH  500 U/L can be improved by high-dose (HD) methotrexate (MTX)
at 5 g/m2 instead of intermediate-dose (ID) MTX at 500 mg/m2 in the preceding study 86; whether 2 therapy courses
are enough for patients with complete resection; and whether combined
systemic and intraventricular chemotherapy is efficacious for central
nervous system-positive (CNS+) patients.
After a cytoreductive prephase, treatment was stratified into 3 risk
groups: patients in R1 (completely resected) received 2 5-day courses
(ID-MTX, dexamethasone, oxazaphorins, etoposide, cytarabine,
doxorubicin, and intrathecal therapy), patients in R2 (extra-abdominal
primary only or abdominal tumor and LDH <500 U/L) received 4 courses
containing HD-MTX, and patients in R3 (abdominal primary and LDH 500
U/L or bone marrow/CNS/multilocal bone disease) received 6 courses.
Incomplete responders after 2 courses received an intensification
containing HD-cytarabine/etoposide. Patients with no or necrotic tumor
thereafter received 3 more courses; 6 patients with viable tumor
received autologous bone marrow transplantation. From April 1990 through March 1995, 413 evaluable patients were enrolled (R1, 17%; R2,
40%; and R3, 43%). The 6-year event-free survival (pEFS) was 89% ± 2% for all and 100%, 96% ±2%, and 78% ± 3% in R1,
R2, and R3, respectively. The pEFS of patients with abdominal stage III
and LDH 500 U/L was 81% ± 4% as compared with 43% ± 10% in
study 86. Of 26 CNS+ patients, 5 died early, but only 3 relapsed.
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