title: Moderate increase of secondary hematologic malignancies after myeloablative radiochemotherapy and autologous stem-cell transplantation in patients with indolent lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group.
abstract: OBJECTIVE
  An increased risk of therapy-related myelodysplastic syndrome (t-MDS) and acute myeloid leukemia (t-AML) after high-dose therapy and autologous stem-cell transplantation (ASCT) for malignant lymphoma has been described by several studies, reporting a highly variable incidence ranging from 1% to 12%. To assess this risk more precisely, the German Low Grade Lymphoma Study Group investigated the incidence of t-MDS/t-AML after ASCT on the basis of a randomized comparison of ASCT versus interferon alfa (IFN-alpha) maintenance in indolent lymphoma.
  
  
  METHODS
  Between 1996 and 2002, 440 patients with indolent lymphoma were randomly assigned after a cyclophosphamide, doxorubicin, vincristine, and prednisone-like induction therapy regimen to myeloablative radiochemotherapy followed by ASCT or IFN-alpha. The incidence of secondary hematologic malignancies was determined by standardized follow-up of all study patients. Bone marrow samples from patients with proven or suspected t-MDS/t-AML were centrally reviewed.
  
  
  RESULTS
  After a median follow-up of 44 months, 431 patients were assessable. Five of 195 patients developed a secondary hematologic malignancy after ASCT. Two of these patients developed a secondary AML. Accordingly, the estimated 5-year risk for secondary hematologic neoplasias after ASCT was 3.8%. In contrast, in the IFN-alpha arm, the 5-year risk of hematologic neoplasias was 0.0% (P = .0248).
  
  
  CONCLUSIONS
  The data of this randomized trial demonstrate an increased risk of secondary hematologic malignancies after myeloablative radiochemotherapy and ASCT compared with conventional chemotherapy. However, as ASCT significantly improves progression-free survival, it is currently not evident to what extent the higher rate of t-MDS/t-AML will diminish the benefit of ASCT in indolent lymphoma.
authors.affiliation: Department of Internal Medicine III, Ludwig-Maximilians-University, University Hospital Grosshadern, Marchioninistrasse 15, 81377 Munich, Germany. georg.lenz@med3.med.uni-muenchen.de
authors.forename: Georg
authors.initials: G
authors.lastname: Lenz
authors.forename: Martin
authors.initials: M
authors.lastname: Dreyling
authors.forename: Eva
authors.initials: E
authors.lastname: Schiegnitz
authors.forename: Torsten
authors.initials: T
authors.lastname: Haferlach
authors.forename: Joerg
authors.initials: J
authors.lastname: Hasford
authors.forename: Michael
authors.initials: M
authors.lastname: Unterhalt
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hiddemann
mesh_terms: D000208:Acute Disease; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007951:Leukemia, Myeloid / Q000453:epidemiology* / Q000209:etiology*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000453:epidemiology* / Q000209:etiology*; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000209:etiology*; D011241:Prednisone / Q000008:administration & dosage; D011446:Prospective Studies; D011878:Radiotherapy; D012307:Risk Factors; D033581:Stem Cell Transplantation; D014182:Transplantation, Autologous; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone