title: Extended exposure to alkylator chemotherapy: delayed appearance of myelodysplasia.
abstract: OBJECTIVE
  A case series of gliomas treated with alkylator-based chemotherapy who subsequently developed myelodysplastic syndrome (tMDS) or acute myelocytic leukemia (AML).
  
  
  BACKGROUND
  Alkylator-based chemotherapy is recognized to be leukemogenic; however, it is infrequently described as a delayed consequence of anti-glioma treatment.
  
  
  METHODS
  Seven patients (4 men; 3 women) ages 34-69 years (median 44), with gliomas (3 Grade 2; 4 Grade 3) were treated with surgery, all but one with involved-field radiotherapy and all with alkylator-based chemotherapy (temozolomide; 6 patients, nitrosoureas; 5 patients, both agents; 5 patients).
  
  
  RESULTS
  Exposure to alkylator-based chemotherapy ranged from 8 to 30 months (median 24). The diagnosis of tMDS was determined by bone marrow biopsy in 7 patients. Seven patients showed chromosomal abnormalities consistent with chemotherapy induced MDS. Three patients were diagnosed with AML as well (in two determined by bone marrow and one at autopsy). Interval from last chemotherapy exposure to diagnosis of tMDS/AML ranged from 3 to 31 months (median 24 months). Two patients were treated with bone marrow transplantation and 5 received supportive care only. Five patients have died, 2 as a consequence of recurrent brain tumor, 1 as a complication of transplantation, and 2 due to AML.
  
  
  CONCLUSIONS
  Although rare, induction of tMDS/AML following extended use of alkylator-based chemotherapy may become more relevant with the evolving practice to treat gliomas for protracted periods. Future work to determine at risk patients would be important.
authors.affiliation: Department of Neurology and Neurological Surgery, University of Washington, DC, USA. chambemc@u.washington.edu
authors.forename: Marc C
authors.initials: MC
authors.lastname: Chamberlain
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Raizer
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000139:chemically induced* / Q000401:mortality; D009607:Nitrosourea Compounds / Q000627:therapeutic use; D012086:Reoperation / Q000706:statistics & numerical data; D016019:Survival Analysis; D017741:Survivors; D000077204:Temozolomide; D013997:Time Factors
chemical_list: D018906:Antineoplastic Agents, Alkylating; D009607:Nitrosourea Compounds; D003606:Dacarbazine; D000077204:Temozolomide