title: High-dose treatment with autologous bone marrow support as consolidation of first remission in younger patients with acute myelogenous leukaemia.
abstract: BACKGROUND
  Debate and controversy remain as to the optimal post-remission therapy for younger patients with acute myelogenous leukaemia (AML). The aim of this study was to evaluate high-dose treatment (HDT) with autologous bone marrow support (ABMS) as consolidation of first complete remission (CR).
  
  
  METHODS
  One hundred forty-four patients (AML-M3 excluded, median age 38 years, range 15-49 years) received remission induction therapy comprising: adriamycin 25 mg/m2, days 1-3, cytosine arabinoside (ara-C) and 6-thioguanine, both at 100 mg/m2 bid, days 1-7. Patients in whom CR was achieved received two further cycles of the same treatment prior to bone marrow being harvested and cryopreserved. HDT comprised ara-C: 1 g/m2 b.i.d. x six days and total body irradiation (TBI): 200 cGy b.i.d. for three days. Thawed autologous marrow was then re-infused.
  
  
  RESULTS
  Complete remission was achieved in 106 of 144 patients (73%) who were thus eligible to receive ara-C + TBI + ABMS; 61 actually received it. Following HDT, the median time to neutrophil recovery (> 0.5 x 10(9)/l) was 25 days (range 11-72 days) and to platelet recovery (> 20 x 10(9)/l), 42 days (range 15-159 days). There were eight treatment-related deaths. Analysis by 'intention to treat' shows both remission duration (log-rank, P = 0.001) and survival (log-rank, P = 0.004) to be significantly longer for the 106 patients eligible to receive HDT than for a historical control group (n = 133) who received identical remission induction and consolidation therapy but without ara-C + TBI + ABMS. With a median follow-up of 5.5 years, 39 of 106 patients remain in CR (37%) and 54 (51% of those in whom CR was achieved) remain alive, with a predicted actuarial survival of 52% at 5 years.
  
  
  CONCLUSIONS
  The addition of ara-C + TBI + ABMS to conventional consolidation therapy significantly improved remission duration and survival over those of a historical control group of patients with AML (aged < 50, AML-M3 excluded). HDT was, however, associated with significant treatment-related mortality and slow blood count recovery. The use of ara-C + TBI supported by peripheral blood progenitor cells should make the treatment safer and more widely applicable in AML.
authors.affiliation: ICRF Medical Oncology Unit, Dept of Medical Oncology, St. Bartholomewis Hospital, London, UK. a.rohatiner@icrf.icnet.uk
authors.forename: A Z
authors.initials: AZ
authors.lastname: Rohatiner
authors.forename: R
authors.initials: R
authors.lastname: Bassan
authors.forename: R
authors.initials: R
authors.lastname: Raimondi
authors.forename: J A
authors.initials: JA
authors.lastname: Amess
authors.forename: S
authors.initials: S
authors.lastname: Arnott
authors.forename: A
authors.initials: A
authors.lastname: Personen
authors.forename: F
authors.initials: F
authors.lastname: Rodeghiero
authors.forename: T
authors.initials: T
authors.lastname: Barbui
authors.forename: M J
authors.initials: MJ
authors.lastname: Bradburn
authors.forename: M
authors.initials: M
authors.lastname: Carter
authors.forename: T A
authors.initials: TA
authors.lastname: Lister
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D003561:Cytarabine / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D011379:Prognosis; D016019:Survival Analysis; D013866:Thioguanine / Q000008:administration & dosage; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014916:Whole-Body Irradiation
chemical_list: D003561:Cytarabine; D004317:Doxorubicin; D013866:Thioguanine