title: Second malignant neoplasms after treatment of childhood acute lymphoblastic leukemia.
abstract: OBJECTIVE
  Second malignant neoplasms (SMNs) after diagnosis of childhood acute lymphoblastic leukemia (ALL) are rare events.
  
  
  METHODS
  We analyzed data on risk factors and outcomes of 642 children with SMNs occurring after treatment for ALL from 18 collaborative study groups between 1980 and 2007.
  
  
  RESULTS
  Acute myeloid leukemia (AML; n = 186), myelodysplastic syndrome (MDS; n = 69), and nonmeningioma brain tumor (n = 116) were the most common types of SMNs and had the poorest outcome (5-year survival rate, 18.1% ± 2.9%, 31.1% ± 6.2%, and 18.3% ± 3.8%, respectively). Five-year survival estimates for AML were 11.2% ± 2.9% for 125 patients diagnosed before 2000 and 34.1% ± 6.3% for 61 patients diagnosed after 2000 (P < .001); 5-year survival estimates for MDS were 17.1% ± 6.4% (n = 36) and 48.2% ± 10.6% (n = 33; P = .005). Allogeneic stem-cell transplantation failed to improve outcome of secondary myeloid malignancies after adjusting for waiting time to transplantation. Five-year survival rates were above 90% for patients with meningioma, Hodgkin lymphoma, thyroid carcinoma, basal cell carcinoma, and parotid gland tumor, and 68.5% ± 6.4% for those with non-Hodgkin lymphoma. Eighty-nine percent of patients with brain tumors had received cranial irradiation. Solid tumors were associated with cyclophosphamide exposure, and myeloid malignancy was associated with topoisomerase II inhibitors and starting doses of methotrexate of at least 25 mg/m(2) per week and mercaptopurine of at least 75 mg/m(2) per day. Myeloid malignancies with monosomy 7/5q- were associated with high hyperdiploid ALL karyotypes, whereas 11q23/MLL-rearranged AML or MDS was associated with ALL harboring translocations of t(9;22), t(4;11), t(1;19), and t(12;21) (P = .03).
  
  
  CONCLUSIONS
  SMNs, except for brain tumors, AML, and MDS, have outcomes similar to their primary counterparts.
authors.affiliation: Department of Paediatric and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark. kschmiegelow@rh.dk
authors.forename: Kjeld
authors.initials: K
authors.lastname: Schmiegelow
authors.forename: Mette Frandsen
authors.initials: MF
authors.lastname: Levinsen
authors.forename: Andishe
authors.initials: A
authors.lastname: Attarbaschi
authors.forename: Andre
authors.initials: A
authors.lastname: Baruchel
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Devidas
authors.forename: Gabriele
authors.initials: G
authors.lastname: Escherich
authors.forename: Brenda
authors.initials: B
authors.lastname: Gibson
authors.forename: Christiane
authors.initials: C
authors.lastname: Heydrich
authors.forename: Keizo
authors.initials: K
authors.lastname: Horibe
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ishida
authors.forename: Der-Cherng
authors.initials: DC
authors.lastname: Liang
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Gérard
authors.initials: G
authors.lastname: Michel
authors.forename: Rob
authors.initials: R
authors.lastname: Pieters
authors.forename: Caroline
authors.initials: C
authors.lastname: Piette
authors.forename: Ching-Hon
authors.initials: CH
authors.lastname: Pui
authors.forename: Susana
authors.initials: S
authors.lastname: Raimondi
authors.forename: Lewis
authors.initials: L
authors.lastname: Silverman
authors.forename: Martin
authors.initials: M
authors.lastname: Stanulla
authors.forename: Batia
authors.initials: B
authors.lastname: Stark
authors.forename: Naomi
authors.initials: N
authors.lastname: Winick
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Valsecchi
mesh_terms: D000293:Adolescent; D001932:Brain Neoplasms / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D053208:Kaplan-Meier Estimate; D059785:Karyotype; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology; D008297:Male; D009190:Myelodysplastic Syndromes / Q000453:epidemiology; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000209:etiology / Q000401:mortality; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate