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Favorable outcome of B-cell acute lymphoblastic leukemia in childhood: a
report of three consecutive studies of the BFM group
A Reiter, M Schrappe, WD Ludwig, F Lampert, J Harbott, G Henze, CM Niemeyer, H Gadner, S Muller-Weihrich and J Ritter
Department of Pediatric Hematology and Oncology, Medizinische Hochschule
Hannover, Germany.
In 1981 the BFM group introduced a new treatment strategy for B-cell acute
lymphoblastic leukemia (B-ALL). A cytoreductive prephase
(prednisone/cyclophosphamide) was followed by eight 5-day courses of
chemotherapy. Fractionated cyclophosphamide, methotrexate (MTX) 0.5 g/m2
(24-hour infusion), and MTX intrathecally were administered at each course
and cytosine arabinoside (ARA-C)/teniposide (VM-26) was given alternately
with doxorubicin. In study ALL-BFM-83, central nervous system (CNS)
chemotherapy was intensified by adding dexamethasone, while MTX/ARA-C was
administered intraventricularly. Therapy duration was reduced to six
courses. In study ALL-BFM-86, MTX 0.5 g/m2 was replaced by high-dose (HD)
MTX, 5 g/m2 (24-hour infusion), and MTX/ARA-C/prednisolone intrathecal
therapy was introduced. Doses of ARA-C and VM-26 were increased and
fractionated, cyclophosphamide was partially replaced by ifosfamide, and
vincristine was added. CNS irradiation was 24 Gy for prevention and 30 Gy
for overt disease in studies ALL-BFM-81 and -83, but was omitted in
ALL-BFM-86. In all, 87 patients were enrolled, 22 (8 CNS-positive) in study
All-BFM-81, 24 (7 CNS-positive) in study ALL-BFM-83, and 41 (0
CNS-positive) in study ALL- BFM-86. The estimated 5-year duration of
event-free survival (EFS) was 43% in study ALL-BFM 81, 50% in study
ALL-BFM-83, and 78% in study ALL- BFM-86 (minimal follow-up, 25 months).
Nineteen of 24 relapses occurred while on therapy or shortly thereafter. In
study ALL-BFM 81, the CNS was the most frequent site of failure. In
ALL-BFM-83, there were no isolated CNS relapses, but more bone marrow (BM)
relapses occurred. In ALL-BFM-86, localized manifestations were the
predominant site of failure, no isolated BM relapses occurred, and only one
CNS relapse was diagnosed. No single parameter exerted a consistent
influence on outcome with one exception. The presence of residual disease
after the first two courses was correlated with an increased risk of
therapy failure. We conclude that an intensive, short-pulse therapy
delivered within a 4-month period is highly effective in the treatment of
B-ALL. In addition to fractionated cyclophosphamide/ifosfamide, a 24-hour
infusion of HD MTX 5 g/m2 in conjunction with an i.th. therapy is an
important component for prevention of both systemic and CNS relapses. CNS
irradiation is not needed for CNS-negative patients.
Volume 80,
Issue 10,
pp. 2471-2478,
11/15/1992
Copyright © 1992 by The American Society of Hematology
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