title: Therapy-related myelodysplasia and secondary acute myelogenous leukemia after high-dose therapy with autologous hematopoietic progenitor-cell support for lymphoid malignancies.
abstract: OBJECTIVE
  To evaluate the incidence of and risk factors for therapy-related myelodysplasia (tMDS) and secondary acute myelogenous leukemia (sAML), after high-dose therapy (HDT) with autologous bone marrow or peripheral-blood progenitor-cell support, in patients with non-Hodgkin's lymphoma (NHL).
  
  
  METHODS
  Between January 1985 and November 1996, 230 patients underwent HDT comprising cyclophosphamide therapy and total-body irradiation, with autologous hematopoietic progenitor-cell support, as consolidation of remission. With a median follow-up of 6 years, 27 (12%) developed tMDS or sAML.
  
  
  RESULTS
  Median time to development of tMDS or sAML was 4.4 years (range, 11 months to 8.8 years) after HDT. Karyotyping (performed in 24 cases) at diagnosis of tMDS or sAML revealed complex karyotypes in 18 patients. Seventeen patients had monosomy 5/5q-, 15 had -7/7q-, seven had -18/18q-, seven had -13/13q-, and four had -20/20q-. Twenty-one patients died from complications of tMDS or sAML or treatment for tMDS or sAML, at a median of 10 months (range, 0 to 26 months). Sixteen died without evidence of recurrent lymphoma. Six patients were alive at a median follow-up of 6 months (range, 2 to 22 months) after diagnosis of tMDS or sAML. On multivariate analysis, prior fludarabine therapy (P =.009) and older age (P =.02) were associated with the development of tMDS or sAML. Increased interval from diagnosis to HDT and bone marrow involvement at diagnosis were of borderline significance (P =.05 and.07, respectively).
  
  
  CONCLUSIONS
  tMDS and sAML are serious complications of HDT for NHL and are associated with very poor prognosis. Alternative strategies for reducing their incidence and for treatment are needed.
authors.affiliation: Imperial Cancer Research Fund Medical Oncology Unit, Department of Medical Oncology, St Bartholomew's Hospital, London.
authors.forename: I N
authors.initials: IN
authors.lastname: Micallef
authors.forename: D M
authors.initials: DM
authors.lastname: Lillington
authors.forename: J
authors.initials: J
authors.lastname: Apostolidis
authors.forename: J A
authors.initials: JA
authors.lastname: Amess
authors.forename: M
authors.initials: M
authors.lastname: Neat
authors.forename: J
authors.initials: J
authors.lastname: Matthews
authors.forename: T
authors.initials: T
authors.lastname: Clark
authors.forename: J M
authors.initials: JM
authors.lastname: Foran
authors.forename: A
authors.initials: A
authors.lastname: Salam
authors.forename: T A
authors.initials: TA
authors.lastname: Lister
authors.forename: A Z
authors.initials: AZ
authors.lastname: Rohatiner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics / Q000401:mortality; D008228:Lymphoma, Non-Hodgkin / Q000150:complications* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics / Q000401:mortality; D016609:Neoplasms, Second Primary / Q000209:etiology* / Q000235:genetics; D017063:Outcome Assessment, Health Care; D012307:Risk Factors; D015996:Survival Rate; D014182:Transplantation, Autologous / Q000009:adverse effects