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Prepublished online as a Blood First Edition Paper on April 30, 2002; DOI 10.1182/blood-2001-12-0371.
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Blood, 1 August 2002, Vol. 100, No. 3, pp. 974-981
NEOPLASIA
MDR1 protein expression is an independent predictor of complete
remission in newly diagnosed adult acute lymphoblastic
leukemia
Agostino Tafuri,
Chiara Gregorj,
Maria T. Petrucci,
Maria R. Ricciardi,
Marco Mancini,
Giuseppe Cimino,
Cristina Mecucci,
Alessandra Tedeschi,
Giuseppe Fioritoni,
Felicetto Ferrara,
Francesco Di
Raimondo,
Eugenio Gallo,
Vincenzo Liso,
Francesco Fabbiano,
Nicola Cascavilla,
Giovanni Pizzolo,
Andrea Camera,
Fabrizio Pane,
Francesco Lanza,
Daniela Cilloni,
Luciana Annino,
Antonella Vitale,
Maria L. Vegna,
Marco Vignetti,
Robin Foà, and
Franco Mandelli for
the GIMEMA Group
From the Dipartimento di Biotecnologie Cellulari ed
Ematologia, University La Sapienza, Roma; Dipartimento di Medicina
Clinica e Sperimentale, University of Perugia; Divisione di Ematologia,
Ospedale Niguarda, Milano; Divisione di Ematologia con Trapianto,
Ospedale Civile, Pescara; Divisione di Ematologia, Ospedale Cardarelli,
Napoli; Cattedra di Ematologia, Ospedale Ferrarotto, Catania;
Ematologia Molinette, Divisione di Medicina, Ospedale S. Giovanni
Battista, Torino; Ematologia Policlinico, University of Bari; Divisione
di Ematologia, Ospedale V. Cervello, Palermo; Ospedale Casa Sollievo
della Sofferenza, S. Giovanni Rotondo; Divisione di Ematologia,
Ospedale Policlinico, University of Verona; Ematologia, University
Federico II, Napoli; Sezione di Ematologia Dipartimento di Scienze
Biomediche Arciospedale S. Anna, Ferrara; Divisione di Medicina Interna
ed Ematologia Azienda Ospedaliera San Luigi Gonzaga, Orbassano Torino;
Sezione Ematologia, Ospedale Umberto I, Frosinone, Italy.
Little is known about the prognostic role of multidrug resistance
(MDR) in adults with newly diagnosed acute lymphoblastic leukemia
(ALL). In the context of the GIMEMA ALL0496 protocol, we evaluated the
impact of MDR1 (protein expression and function) on the achievement of
complete remission (CR) and clinical outcome. Flow cytometric analysis
of MDR1 expression (D) and function (rhodamine-123 efflux)
was obtained in 203 and 158 patients, respectively. MDR1 expression was
detected in 44 (21.7%) of 203 patients, and function was found in 23 (14.6%) of 158 (14.6%) patients. Expression of the multidrug
resistance-associated protein 1 (MRP1) and lung-resistance protein
(LRP) evaluated in 43 samples was found in 13 and 26 patients, respectively. Among the 200 patients evaluable for the clinical correlation study, 125 (79.6%) of 157 without MDR1 expression achieved
CR compared with 23 (53.5%) of 43 with MDR1 expression (P = .001). At univariate analysis, MDR1 expression was
significantly associated with CR when considered as a dichotomized
(P = .001) or continuous (P = .01)
variable. At multivariate analysis, dichotomized evaluation of MDR1
expression independently predicted CR (P = .004) with age
(P = .03) and CD34 (P = .03); as a
continuous variable, MDR1 expression (P = .03) was the
only significant factor other than CD34 (P = .01). MDR1
function failed to predict achievement of CR or of MRP1 and LRP
expression. MDR1 expression did not correlate with CR duration, nor did
it predict for survival duration. These results demonstrate that MDR1
expression in de novo adult ALL is an independent predictor of CR achievement.
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