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Prepublished online as a Blood First Edition Paper on April 30, 2002; DOI 10.1182/blood-2001-12-0371.
Submitted December 28, 2001
Accepted March 20, 2002
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, Guiseppe Fioritoni, Felicetto Ferrara, Francesco Di Raimondo, Eugenio Gallo, Vincenzo Liso, Francesco Fabbiano, Nicola Cascavilla, Giovanni Pizzolo, Andrea Camera, Fabrizio Pane, Francesco Lanza, and Daniela Cilloni
Biotecnologie Cellulari ed Ematologia, University La Sapienza of Rome, Roma, Italy
Medicina Clinica e Sperimentale, University of Perugia, Perugia, Italy
Divisione di Ematologia, Ospedale Niguarda, Milano, Italy
Divisione di Ematologia con Trapianto, Ospedale Civile, Pescara, Italy
Divisione di Ematologia, Ospedale Cardarelli, Napoli, Italy
Cattedra di Ematologia, Ospedale Ferrarotto, Catania, Italy
Ematologia Molinette, Divisione di Medicina, Ospedale S. Giovanni Battista, Torino, Italy
Ematologia Policlinico, University of Bari, Bari, Italy
Divisione di Ematologia, Ospedale V. Cervello, Palermo, Italy
Casa Sollievo della Sofferenza, Ospedale di S. Giovanni Rotondo, S. Giovanni Rotondo, Italy
Divisione di Ematologia, Ospedale Policlinico, Verona, Italy
Ematologia, University Federico II, Napoli, Italy
Dipartimento di Scienze Biomediche Arciospedale S. Anna, Sezione di Ematologia, Ferrara, Italy
Divisione di Medicina Interna ed Ematologia, Azienda Ospedaliera San Luigi Gonzaga, Orbassano Torino, Italy
* Corresponding author; email: agotaf{at}bce.med.uniroma1.it.
Little is known on 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-value) and function (Rhodamine-123 efflux) was obtained in 203 and 158 cases, respectively. MDR1 expression was detected in 44/203 patients (21.7%), while the function was found in 23/158 cases (14.6%). Expression of the multidrug resistance-associated protein 1 (MRP1) and lung-resistance protein (LRP) evaluated in 43 samples was found in 13 and 26 of cases, respectively. Among the 200 patients evaluable for the clinical correlation study, 125/157 (79.6%) without MDR1 expression achieved CR compared to 23/43 (53.5%) with MDR1 expression (P=0.001). At univariate analysis, MDR1 expression was significantly associated with CR when considered as a dichotomized (P=0.001) or continuous (P=0.01) variable. At multivariate analysis, dichotomized evaluation of MDR1 expression independently predicted CR (P=0.004) with age (P=0.03) and CD34 (P=0.03); as a continuous variable, MDR1 expression (P=0.03) was the only significant factor other than CD34 (P=0.01). MDR1 function failed to predict achievement of CR, as well as 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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