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Blood, Vol. 95 No. 9 (May 1), 2000:
pp. 2770-2775
Secondary neoplasms subsequent to Berlin-Frankfurt-Münster
therapy of acute lymphoblastic leukemia in childhood: significantly
lower risk without cranial radiotherapy
Lutz Löning,
Martin Zimmermann,
Alfred Reiter,
Peter Kaatsch,
Günter Henze,
Hansjörg Riehm, and
Martin Schrappe
From the Department of Pediatric Hematology and Oncology, Hannover
Medical School, Hannover; the Department of Pediatric Oncology,
University Children's Hospital Giessen; the Department of Pediatric
Oncology, University Hospital Rudolf-Virchow, Charité Berlin; and
the German Childhood Cancer Registry, University Mainz, Germany.
Secondary neoplasms (SNs) represent serious late
complications after successful treatment of malignant diseases. To
evaluate the rate and type of SNs after Berlin-Frankfurt-Münster
(BFM) treatment in children with acute lymphoblastic leukemia (ALL), we
analyzed the data from the BFM database and the German Childhood Cancer
Registry (GCCR). Between April 1979 and April 1995, 5006 children with
B-precursor or T-ALL were enrolled in 5 ALL-BFM multicenter trials. The
median follow-up time from diagnosis was 5.7 years (range 1.5-18 years). By December 1997, 52 SNs were documented, including 16 acute
myeloid leukemias (AMLs), 13 neoplasms of the central
nervous system (CNS), and 23 other neoplasms. Compared with the expected numbers estimated from incidence rates derived from
the GCCR, this represented a 14-fold increase for all cancers and a
19-fold increase for CNS tumors. SNs developed 0.9 to 15 years (median:
6 years) after the diagnosis of ALL; 46 patients were in first complete
remission (CR). The overall cumulative risk of SNs at 15 years was
3.3% (95% confidence interval [CI]: 1.6%-5.1%) and 2.9% (95%
CI: 1.6%-4.2%) in first CR. The risk was 3.5% (95% CI: 1.5%-5.5%)
after treatment, including cranial irradiation and significantly lower
in nonirradiated patients: 1.2% (95% CI: 0.2%-2.3%;
P = .048). The development of secondary AML was not
associated with the use of any specific cytotoxic agent. Considering
the high-survival rate of this large unselected ALL cohort, the risk of
SN is relatively low, though higher, especially after cranial
irradiation, than in the general population. Long-term follow-up is
mandatory, and further SNs with longer latency periods are to be expected.
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