title: Acute myeloid leukemia and myelodysplastic syndromes after radiation therapy are similar to de novo disease and differ from other therapy-related myeloid neoplasms.
abstract: OBJECTIVE
  Therapy-related myeloid neoplasms (t-MN) represent a unique clinical syndrome occurring in patients treated with chemotherapy and/or external-beam radiation (XRT) and are characterized by poorer prognosis compared with de novo disease. XRT techniques have evolved in recent years and are associated with significantly reduced bone marrow exposure. The characteristics of post-XRT t-MN in the current era have not been studied.
  
  
  METHODS
  We analyzed patients who developed acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) after XRT alone (47 patients) or cytotoxic chemotherapy/combined-modality therapy (C/CMT, 181 patients) and compared them with patients with de novo MDS or AML (222 patients). We estimated bone marrow exposure to radiation and compared the clinical, pathologic, and cytogenetic features and outcome of the XRT patients with the C/CMT patients and with patients with de novo MDS and AML.
  
  
  RESULTS
  Patients with t-MN after XRT alone had superior overall survival (P = .006) and lower incidence of high-risk karyotypes (P = .01 for AML and < .001 for MDS) compared with patients in the C/CMT group. In contrast, there were no significant differences in survival or frequency of high-risk karyotypes between the XRT and de novo groups.
  
  
  CONCLUSIONS
  AML and MDS diagnosed in the past decade in patients after receiving XRT alone differ from t-MN occurring after C/CMT and share genetic features and clinical behavior with de novo AML/MDS. Our results suggest that post-XRT MDS/AML may not represent a direct consequence of radiation toxicity and warrant a therapeutic approach similar to de novo disease.
authors.affiliation: Massachusetts General Hospital, 55 Fruit St, Warren 225, Boston, MA 02114, USA.
authors.forename: Valentina
authors.initials: V
authors.lastname: Nardi
authors.forename: Karen M
authors.initials: KM
authors.lastname: Winkfield
authors.forename: Chi Young
authors.initials: CY
authors.lastname: Ok
authors.forename: Andrzej
authors.initials: A
authors.lastname: Niemierko
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kluk
authors.forename: Eyal C
authors.initials: EC
authors.lastname: Attar
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Sa A
authors.initials: SA
authors.lastname: Wang
authors.forename: Robert P
authors.initials: RP
authors.lastname: Hasserjian
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D009381:Neoplasms, Radiation-Induced / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D016609:Neoplasms, Second Primary / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D055815:Young Adult