title: Case-control study of multidrug resistance phenotype and response to induction treatment including or not fludarabine in newly diagnosed acute myeloid leukaemia patients.
abstract: One hundred and six patients aged </=60 years with newly diagnosed acute myeloid leukaemia (AML) treated with fludarabine-based regimens (cases) were matched with 106 AML patients treated with conventional non-fludarabine-based regimens (controls). The cases and controls were matched by expression of the multidrug resistance P-glycoprotein (MDR-Pgp), measured by flow cytometry as mean fluorescence index (MFI), cytogenetics, and age. The complete remission (CR) rate of the cases was 61% among the MDR-Pgp-positive (pos(ve)) patients (MFI >/= 6) vs. 75% among the MDR-Pgp-negative (neg(ve)) ones (MFI < 6) (P = 0.16). Conversely, in the controls, the CR rate was 44% among the MDR-Pgp-pos(ve) patients vs. 67% among the MDR-Pgp-neg(ve) ones (P = 0.02). The 4-year disease-free survival (DFS) and overall survival (OS) of MDR-Pgp-pos(ve) cases were significantly longer than those of MDR-Pgp-pos(ve) controls (DFS, 28.1% vs. 6.5%, P = 0.004; OS, 33.5% vs. 9.6%, P = 0.01). This difference was not found among the MDR-Pgp-neg(ve) patients. By univariate (P = 0.007) and multivariate (P = 0.007) analysis, the MDR-Pgp-pos(ve) phenotype was negatively correlated with CR and it emerged as the most important independent negative prognostic factor, after cytogenetics. Our study confirms the prognostic impact of the MDR phenotype in AML and strongly suggests fludarabine-based induction treatments as a promising strategy for MDR-Pgp-pos(ve) AML patients. In this setting of patients, large prospective randomised studies should be planned.
authors.affiliation: Chair of Haematology, Unit of Blood Diseases and Cell Therapies, University of Brescia, Brescia, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Malagola
authors.forename: Daniela
authors.initials: D
authors.lastname: Damiani
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.forename: Angela
authors.initials: A
authors.lastname: Michelutti
authors.forename: Bruno
authors.initials: B
authors.lastname: Cesana
authors.forename: Antonio De
authors.initials: AD
authors.lastname: Vivo
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Piccaluga
authors.forename: Emanuela
authors.initials: E
authors.lastname: Ottaviani
authors.forename: Anna
authors.initials: A
authors.lastname: Candoni
authors.forename: Antonella
authors.initials: A
authors.lastname: Geromin
authors.forename: Mario
authors.initials: M
authors.lastname: Tiribelli
authors.forename: Renato
authors.initials: R
authors.lastname: Fanin
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Testoni
authors.forename: Francesco
authors.initials: F
authors.lastname: Lauria
authors.forename: Monica
authors.initials: M
authors.lastname: Bocchia
authors.forename: Marco
authors.initials: M
authors.lastname: Gobbi
authors.forename: Ivana
authors.initials: I
authors.lastname: Pierri
authors.forename: Alfonso
authors.initials: A
authors.lastname: Zaccaria
authors.forename: Eliana
authors.initials: E
authors.lastname: Zuffa
authors.forename: Patrizio
authors.initials: P
authors.lastname: Mazza
authors.forename: Giancarla
authors.initials: G
authors.lastname: Priccolo
authors.forename: Luigi
authors.initials: L
authors.lastname: Gugliotta
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bonini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Visani
authors.forename: Cristina
authors.initials: C
authors.lastname: Skert
authors.forename: Cesare
authors.initials: C
authors.lastname: Bergonzi
authors.forename: Aldo Maria
authors.initials: AM
authors.lastname: Roccaro
authors.forename: Carla
authors.initials: C
authors.lastname: Filí
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
authors.forename: Domenico
authors.initials: D
authors.lastname: Russo
mesh_terms: D000208:Acute Disease; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D018432:Drug Resistance, Multiple; D005260:Female; D006801:Humans; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D012074:Remission Induction; D018709:Statistics, Nonparametric; D015996:Survival Rate; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D014740:Vidarabine; C024352:fludarabine