title: Neuroblastoma and treatment-related myelodysplasia/leukemia: the Memorial Sloan-Kettering experience and a literature review.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. kushnerb@mskcc.org
authors.forename: B H
authors.initials: BH
authors.lastname: Kushner
authors.forename: N K
authors.initials: NK
authors.lastname: Cheung
authors.forename: K
authors.initials: K
authors.lastname: Kramer
authors.forename: G
authors.initials: G
authors.lastname: Heller
authors.forename: S C
authors.initials: SC
authors.lastname: Jhanwar
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D002173:Cancer Care Facilities; D006801:Humans; D007951:Leukemia, Myeloid / Q000139:chemically induced*; D009190:Myelodysplastic Syndromes / Q000139:chemically induced*; D009447:Neuroblastoma / Q000188:drug therapy*; D009518:New York
chemical_list: D000970:Antineoplastic Agents