title: Childhood high-risk acute lymphoblastic leukemia in first remission: results after chemotherapy or transplant from the AIEOP ALL 2000 study.
abstract: The outcome of high-risk (HR) acute lymphoblastic leukemia patients enrolled in the AIEOP-BFM ALL 2000 study in Italy is described. HR criteria were minimal residual disease (MRD) levels ≥10(-3) at day 78 (MRD-HR), no complete remission (CR) at day 33, t(4;11) translocation, and prednisone poor response (PPR). Treatment (2 years) included protocol I, 3 polychemotherapy blocks, delayed intensification (protocol IIx2 or IIIx3), cranial radiotherapy, and maintenance. A total of 312 HR patients had a 5-year event-free survival (EFS) of 58.9% (standard error [SE] = 2.8) and an overall survival of 68.9% (SE = 2.6). In hierarchical order, EFS was 45.9% (4.4) in 132 MRD-HR patients, 41.2% (11.9) in 17 patients with no CR at day 33, 36.4% (14.5) in 11 patients with t(4;11), and 74.0% (3.6) in 152 HR patients only for PPR. No statistically significant difference was found for disease-free survival in patients with very HR features [MRD-HR, no CR at day 33, t(4;11) translocation], given hematopoietic stem cell transplantation (HSCT) (n = 66) or chemotherapy only (n = 88), after adjusting for waiting time to HSCT (5.7 months). Patients at HR only for PPR have a favorable outcome. MRD-HR is associated with poor outcome despite intensive treatment and/or HSCT and may qualify for innovative therapies. The study was registered at www.clinicaltrials.gov as #NCT00613457.
authors.affiliation: Department of Pediatrics, Ospedale S. Gerardo, University of Milano-Bicocca, Fondazione MBBM, Monza, Italy;
authors.forename: Valentino
authors.initials: V
authors.lastname: Conter
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Valsecchi
authors.forename: Rosanna
authors.initials: R
authors.lastname: Parasole
authors.forename: Maria Caterina
authors.initials: MC
authors.lastname: Putti
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Elena
authors.initials: E
authors.lastname: Barisone
authors.forename: Luca
authors.initials: L
authors.lastname: Lo Nigro
authors.forename: Nicola
authors.initials: N
authors.lastname: Santoro
authors.forename: Maurizio
authors.initials: M
authors.lastname: Aricò
authors.forename: Ottavio
authors.initials: O
authors.lastname: Ziino
authors.forename: Andrea
authors.initials: A
authors.lastname: Pession
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Testi
authors.forename: Concetta
authors.initials: C
authors.lastname: Micalizzi
authors.forename: Fiorina
authors.initials: F
authors.lastname: Casale
authors.forename: Marco
authors.initials: M
authors.lastname: Zecca
authors.forename: Gabriella
authors.initials: G
authors.lastname: Casazza
authors.forename: Paolo
authors.initials: P
authors.lastname: Tamaro
authors.forename: Gaetano
authors.initials: G
authors.lastname: La Barba
authors.forename: Lucia Dora
authors.initials: LD
authors.lastname: Notarangelo
authors.forename: Daniela
authors.initials: D
authors.lastname: Silvestri
authors.forename: Antonella
authors.initials: A
authors.lastname: Colombini
authors.forename: Carmelo
authors.initials: C
authors.lastname: Rizzari
authors.forename: Andrea
authors.initials: A
authors.lastname: Biondi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Masera
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D008297:Male; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D011878:Radiotherapy; D012074:Remission Induction; D016896:Treatment Outcome