Case-control study of multidrug resistance phenotype and response to induction treatment including or not fludarabine in newly diagnosed acute myeloid leukaemia patients.
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.
Malagola
Michele
M
Chair of Haematology, Unit of Blood Diseases and Cell Therapies, University of Brescia, Brescia, Italy.
Damiani
Daniela
D
Martinelli
Giovanni
G
Michelutti
Angela
A
Cesana
Bruno
B
Vivo
Antonio De
AD
Piccaluga
Pier Paolo
PP
Ottaviani
Emanuela
E
Candoni
Anna
A
Geromin
Antonella
A
Tiribelli
Mario
M
Fanin
Renato
R
Testoni
Nicoletta
N
Lauria
Francesco
F
Bocchia
Monica
M
Gobbi
Marco
M
Pierri
Ivana
I
Zaccaria
Alfonso
A
Zuffa
Eliana
E
Mazza
Patrizio
P
Priccolo
Giancarla
G
Gugliotta
Luigi
L
Bonini
Alessandro
A
Visani
Giuseppe
G
Skert
Cristina
C
Bergonzi
Cesare
C
Roccaro
Aldo Maria
AM
Filí
Carla
C
Baccarani
Michele
M
Russo
Domenico
D
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
D014740:Vidarabine; C024352:fludarabine