Journal of Clinical Oncology, Vol 16, 3880-3889, Copyright © 1998 by American Society of Clinical Oncology
Neuroblastoma and treatment-related myelodysplasia/leukemia: the Memorial Sloan-Kettering experience and a literature review
BH Kushner, NK Cheung, K Kramer, G Heller and SC Jhanwar
Department of Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. kushnerb@mskcc.org
PURPOSE: To assess treatment-related myelodysplasia/leukemia (t-AML) in
neuroblastoma patients by a review of the Memorial Sloan-Kettering Cancer
Center (MSKCC) data and the literature. PATIENTS AND METHODS: We studied
380 previously untreated and treated MSKCC patients. Low-risk patients
received no cytotoxic therapy. High-risk patients received the N4, N5, or
N6 regimens. Dosing per cycle and cumulative dosing of leukemogenic agents
peaked with N6, which included four cycles of cyclophosphamide 4,200 mg/m2
and doxorubicin 75 mg/m2, plus three cycles of cisplatin 200 mg/m2 and
etoposide 600 mg/m2. We reviewed the literature. RESULTS: t-AML occurred in
six MSKCC patients, which included three of 53 patients in whom the only
chemotherapy consisted of N6, and three patients treated for relapsed or
refractory neuroblastoma; no case of leukemia emerged among the 50 low-risk
patients. Four cases were found incidentally in routine follow-up bone
marrow tests. The 36-month cumulative incidence of t-AML in the N6 cohort
was 7% (95% confidence interval, 0 to 15). Published data parallel the
MSKCC experience in that t-AML after neuroblastoma was once rare but has
become less so since the mid-1980s, when the intensified use of
topoisomerase-II inhibitors and alkylators first gained wide acceptance and
produced better response rates and longer survival. CONCLUSION:
Neuroblastoma itself is not associated with a host susceptibility to
leukemia. However, current neuroblastoma treatment programs that use
high-dose cyclophosphamide, cisplatin, and topoisomerase-II inhibitors may
entail a considerable risk for t-AML. The incidence of t-AML in
neuroblastoma patients may be underestimated because treatment and clinical
factors can mask its presence. Efforts to devise effective but less
leukemogenic treatment for neuroblastoma or to truncate leukemogenic
therapy, eg, by exploiting molecular techniques for the early
identification of complete remission, are warranted.
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