title: Improved outcome in high-risk childhood acute lymphoblastic leukemia defined by prednisone-poor response treated with double Berlin-Frankfurt-Muenster protocol II.
abstract: One hundred ninety-eight children and adolescents were entered in the Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP)-ALL95 study for high-risk acute lymphoblastic leukemia (ALL). Inclusion criteria were poor response to initial prednisone/intrathecal methotrexate (prednisone-poor response [PPR]), resistance to induction therapy, translocation t(9;22), infants with the t(4;11), or CD10(-) ALL. The event-free survival (EFS) rate at 4 years was 56.5% (SE, 3.9%) for the entire group. The overall EFS rate in the current study was significantly better (P =.002) than that obtained in a comparable group of patients treated in the early 1990s in the AIEOP-ALL91 study. In particular, patients with PPR had a 4-year EFS of 61.1% (SE, 4.4%) versus 42.8% (SE, 5.4%) in the ALL 91 study (P =.008). Among PPR patients, those who were PPR-only (60.1%)-that is, they achieved CR and were negative for t(9;22) and t(4;11) translocations-had the best outcomes with this intensive treatment, even when additional adverse features (hyperleukocytosis, T phenotype) were present (4-year EFS, 70.1%; SE, 4.7%). We attribute this improvement to the replacement of 6 alternating blocks of non-cross-resistant drugs with an 8-drug reinduction regimen (Berlin-Frankfurt-Muenster [BFM] protocol II), repeated twice, in the context of a standard BFM-type intensive chemotherapy for high-risk ALL. This modified therapy may lead to high cure rates for patients defined as at high risk for intrinsic resistance to corticosteroids only.
authors.affiliation: Onco-Ematologia Pediatrica, Ospedale dei Bambini G. Di Cristina, Palermo, Italy. arico@ospedalecivicopa.org
authors.forename: Maurizio
authors.initials: M
authors.lastname: Aricò
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Valsecchi
authors.forename: Valentino
authors.initials: V
authors.lastname: Conter
authors.forename: Carmelo
authors.initials: C
authors.lastname: Rizzari
authors.forename: Andrea
authors.initials: A
authors.lastname: Pession
authors.forename: Chiara
authors.initials: C
authors.lastname: Messina
authors.forename: Elena
authors.initials: E
authors.lastname: Barisone
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Poggi
authors.forename: Giulio
authors.initials: G
authors.lastname: De Rossi
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Micalizzi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Masera
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D011241:Prednisone / Q000627:therapeutic use; D012074:Remission Induction / Q000379:methods; D018570:Risk Assessment; D016019:Survival Analysis; D013866:Thioguanine / Q000008:administration & dosage; D014178:Translocation, Genetic; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D000305:Adrenal Cortex Hormones; D003561:Cytarabine; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D001215:Asparaginase; D013866:Thioguanine; D011241:Prednisone