title: Treatment reduction in highly selected standard-risk childhood acute lymphoblastic leukemia. The AIEOP ALL-9501 study.
abstract: OBJECTIVE
  Treatment of childhood standard-risk (SR) acute lymphoblastic leukemia (ALL) is generally successful. However, intensive chemotherapy regimens may be associated with severe treatment sequelae. Efforts are therefore being made to identify those patients in whom less intensive treatment would be equally successful but cause fewer long-term sequelae. The aim of this study was to evaluate the efficacy of treatment reduction in a subset of children with ALL at minimal risk of failure.
  
  
  METHODS
  The population of patients with SR ALL included children aged between 1 and 6 years with less than 20,000 WBC/mm3, non-T immunophenotype, DNA index between 1.16 and 1.6, absence of t(9;22) and t(4;11) clonal translocations, no extramedullary leukemia, good response to prednisone and complete remission (CR) at the end of induction therapy. A reduced-intensity, BFM-type treatment schedule (AIEOP-ALL 9501 protocol) was used. Induction therapy was based on vincristine, prednisone, L-asparaginase and intrathecal methotrexate only; high-dose-methotrexate (2 g/m2) was given x4. The BFM Protocol II was given as reinduction therapy; thus the total dose of anthracyclines was 120 mg/m2 and no epipodophyllotoxins or cranial irradiation were employed.
  
  
  RESULTS
  Between May 1995 and December 1999, 123 patients were identified as having SR-ALL (7.8% of the ALL-95 population), of whom 102 received the SR protocol. After a median follow-up of 5.9 years, 11 patients in the SR protocol had relapsed, 1 had died in remission, and 1 had developed a second malignant neoplasm. The probabilities (standard errors) of survival and event-free survival (EFS) were, respectively, 97.0% (1.7) and 86.7% (3.5) at 5 years, and 95.3% (2.4) and 86.7% (3.5) at 7 years.
  
  
  CONCLUSIONS
  Although most of the relapsed patients were rescued, the long-term EFS probability in this small, highly selected group of patients remains inferior to expectation. Thus, alternative selection criteria, such as treatment response measured by minimal residual disease, should be considered to address the issue of treatment reduction.
authors.affiliation: Oncoematologia Pediatrica, Ospedale dei Bambini G. Di Cristina, 90134 Palermo, Italy. arico@ospedalecivicopa.org
authors.forename: Maurizio
authors.initials: M
authors.lastname: Aricò
authors.forename: Valentino
authors.initials: V
authors.lastname: Conter
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Valsecchi
authors.forename: Carmelo
authors.initials: C
authors.lastname: Rizzari
authors.forename: Marie France Pinta
authors.initials: MF
authors.lastname: Boccalatte
authors.forename: Elena
authors.initials: E
authors.lastname: Barisone
authors.forename: Chiara
authors.initials: C
authors.lastname: Messina
authors.forename: Giulio
authors.initials: G
authors.lastname: De Rossi
authors.forename: Luca
authors.initials: L
authors.lastname: Lo Nigro
authors.forename: Andrea
authors.initials: A
authors.lastname: Pession
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Concetta
authors.initials: C
authors.lastname: Micalizzi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001215:Asparaginase / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003630:Daunorubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology*; D011241:Prednisone / Q000627:therapeutic use; D012307:Risk Factors; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D014750:Vincristine; D001215:Asparaginase; D011241:Prednisone; D003630:Daunorubicin