title: Late intensification chemotherapy has not improved the results of intensive chemotherapy in adult acute lymphoblastic leukemia. Results of a prospective multicenter randomized trial (PETHEMA ALL-89). Spanish Society of Hematology.
abstract: OBJECTIVE
  Intensive induction and post-remission therapies have improved the prognosis in adult acute lymphoblastic leukemia (ALL). However, different from children, the impact of late intensification therapy in the overall results of treatment has not been consistently evaluated. The objective of this study was to analyze the results of a multicenter prospective protocol, PETHEMA ALL-89, in which, after intensive induction and consolidation therapy, randomization to receive delayed intensification treatment was performed.
  
  
  METHODS
  One hundred and eight adults (age > or = 15 years) diagnosed with ALL (ALL L3 excluded) in 22 Spanish hospitals from 1989 to 1994 were treated with a five-drug induction therapy, followed by four cycles of early post-remission treatment during four months, and maintenance therapy for two years. Patients in remission at the end of the first year were randomized to receive one six-week cycle of late intensification therapy. Uni- and multivariate analyses of early response to treatment, complete remission (CR), leukemia-free survival (LFS) and overall survival (OS) were performed.
  
  
  RESULTS
  The median (range) age of the series was 28 (15-74) years and leukocyte count 26 x 10(9)/L (1-600). ALL L1/L2 was present in 38/70 patients, early pre-B in 13, common in 53, pre-B in 12 and T in 30 cases. The CR rate was 86%, and refractory disease 9%. Median LFS was 34 months, with a 5-yr probability of 41% (95% CI, 29-53), whereas median OS was 51 months and 5-year probability 47% (34-59%). There were no differences in either LFS and OS between patients who did or did not receive delayed intensification therapy. Prognostic factors for CR attainment were advanced age and slow response to therapy. These two features were, in addition to high leukocyte counts, the parameters with negative influence in both LFS and OS.
  
  
  CONCLUSIONS
  The results of PETHEMA ALL-89 are similar to those referred in other chemotherapy-based protocols in adult ALL. Delayed intensification has not improved the length of remission and survival. Efforts to improve the prognosis of adult ALL patients must be mainly focused in early intensification treatment.
authors.affiliation: Hematology Department, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain. jmribera@as.hugtip.scs.es
authors.forename: J M
authors.initials: JM
authors.lastname: Ribera
authors.forename: J J
authors.initials: JJ
authors.lastname: Ortega
authors.forename: A
authors.initials: A
authors.lastname: Oriol
authors.forename: M
authors.initials: M
authors.lastname: Fontanillas
authors.forename: J M
authors.initials: JM
authors.lastname: Hernández-Rivas
authors.forename: S
authors.initials: S
authors.lastname: Brunet
authors.forename: J
authors.initials: J
authors.lastname: García-Conde
authors.forename: J
authors.initials: J
authors.lastname: Maldonado
authors.forename: J
authors.initials: J
authors.lastname: Zuazu
authors.forename: S
authors.initials: S
authors.lastname: Gardella
authors.forename: J
authors.initials: J
authors.lastname: Besalduch
authors.forename: P
authors.initials: P
authors.lastname: León
authors.forename: J
authors.initials: J
authors.lastname: Macià
authors.forename: A
authors.initials: A
authors.lastname: Domingo-Albós
authors.forename: E
authors.initials: E
authors.lastname: Feliu
authors.forename: J F
authors.initials: JF
authors.lastname: San Miguel
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011379:Prognosis; D011446:Prospective Studies; D012074:Remission Induction / Q000379:methods; D013030:Spain; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome