title: Secondary malignant neoplasms after intensive treatment of relapsed acute lymphoblastic leukaemia in childhood.
abstract: OBJECTIVE
  To investigate the cumulative incidence of and the risk factors for developing second malignant neoplasms (SMN) in children and adolescents following treatment for relapse of acute lymphocytic leukaemia (ALL).
  
  
  METHODS
  Patients (1376) up to 18 years of age with first relapse of non-B-cell ALL were treated and achieved a 2nd complete remission (CR). The treatment followed trial protocol in five consecutive multicentre trials of the ALL-REZ BFM Study Group between March 1983 and December 2001. The incidence of SMN was analysed, correlated with clinical and therapeutic parameters, and compared to the age-specific incidence rates of cancers as cited in German cancer registries.
  
  
  RESULTS
  Out of the 1376 patients 21 were diagnosed with SMN including non-lymphoblastic leukaemia/myelodysplastic syndrome (n=6), osteo-/Ewing's-/fibroblastic sarcoma (n=4), B-cell ALL/lymphoma (n=2), thyroid carcinoma (n=2), basal cell carcinoma, adeno carcinoma, squamous cell carcinoma, meningioma, malignant histiocytosis, glioblastoma and anaplastic astrocytoma (n=1 each). The overall cumulative risk of SMN at 15 years (median follow-up of 13.1 years) was 1.26%+/-0.38% (SE). SMN was found to be significantly associated with stem cell transplantation (SCT), and high cumulative doses of cranial irradiation, etoposide and cyclophosphamide. In multivariate analysis etoposide (VP16) and cyclophophamide (CY) were found to be independently associated with SMN (p=0.047 and 0.002). Compared to the incidence of neoplasm in the age-matched population, there was a 10-fold increase of neoplasia.
  
  
  CONCLUSIONS
  Despite repeated exposure to intense frontline and relapse treatment (including multiagent chemotherapy, cranial irradiation and stem cell transplantation in some patients) the cumulative incidence of SMN was unexpectedly low, though significantly higher than in the general age-matched population. The association of SMN to SCT seemed to be a secondary effect at least partially mediated by exposure to high doses of VP16 and CY given for conditioning therapy.
authors.affiliation: Charité Universitätsmedizin Berlin, OHC, Klinik für Pädiatrie m.S. Onkologie/Hämatologie, Berlin, Germany. anja.borgmann@charite.de
authors.forename: Anja
authors.initials: A
authors.lastname: Borgmann
authors.forename: Christina
authors.initials: C
authors.lastname: Zinn
authors.forename: Reinhard
authors.initials: R
authors.lastname: Hartmann
authors.forename: Ralf
authors.initials: R
authors.lastname: Herold
authors.forename: Peter
authors.initials: P
authors.lastname: Kaatsch
authors.forename: Gabriele
authors.initials: G
authors.lastname: Escherich
authors.forename: Anja
authors.initials: A
authors.lastname: Möricke
authors.forename: Günter
authors.initials: G
authors.lastname: Henze
authors.forename: Arend
authors.initials: A
authors.lastname: von Stackelberg
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D015337:Multicenter Studies as Topic; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000401:mortality; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000628:therapy*; D012074:Remission Induction; D012307:Risk Factors; D055502:Secondary Prevention