Case-control study of multidrug resistance phenotype and response to induction treatment including or not fludarabine in newly diagnosed acute myeloid leukaemia patients

Michele Malagola, Daniela Damiani, Giovanni Martinelli, Angela Michelutti, Bruno Cesana, Antonio De Vivo, Pier Paolo Piccaluga, Emanuela Ottaviani, Anna Candoni, Antonella Geromin, Mario Tiribelli, Renato Fanin, Nicoletta Testoni, Francesco Lauria, Monica Bocchia, Marco Gobbi, Ivana Pierri, Alfonso Zaccaria, Eliana Zuffa, Patrizio Mazza & 10 others Giancarla Priccolo, Luigi Gugliotta, Alessandro Bonini, Giuseppe Visani, Cristina Skert, Cesare Bergonzi, Aldo Maria Roccaro, Carla Filí, Michele Baccarani, Domenico Russo

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 (posve) patients (MFI ≥ 6) vs. 75% among the MDR-Pgp-negative (negve) ones (MFI <6) (P = 0.16). Conversely, in the controls, the CR rate was 44% among the MDR-Pgp-posve 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-posve cases were significantly longer than those of MDR-Pgp-posve 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-negve patients. By univariate (P = 0.007) and multivariate (P = 0.007) analysis, the MDR-Pgp-posve 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-posve AML patients. In this setting of patients, large prospective randomised studies should be planned.

Original languageEnglish
Pages (from-to)87-95
Number of pages9
JournalBritish Journal of Haematology
Volume136
Issue number1
DOIs
Publication statusPublished - Jan 2007

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Multiple Drug Resistance
P-Glycoprotein
Acute Myeloid Leukemia
Case-Control Studies
Phenotype
Therapeutics
Fluorescence
Cytogenetics
Disease-Free Survival
fludarabine
Survival
Flow Cytometry
Prospective Studies

Keywords

  • Acute myeloid leukaemia
  • Fludarabine
  • Multidrug-resistance

ASJC Scopus subject areas

  • Hematology

Cite this

Case-control study of multidrug resistance phenotype and response to induction treatment including or not fludarabine in newly diagnosed acute myeloid leukaemia patients. / Malagola, Michele; Damiani, Daniela; Martinelli, Giovanni; Michelutti, Angela; Cesana, Bruno; Vivo, Antonio De; Piccaluga, Pier Paolo; Ottaviani, Emanuela; Candoni, Anna; Geromin, Antonella; Tiribelli, Mario; Fanin, Renato; Testoni, Nicoletta; Lauria, Francesco; Bocchia, Monica; Gobbi, Marco; Pierri, Ivana; Zaccaria, Alfonso; Zuffa, Eliana; Mazza, Patrizio; Priccolo, Giancarla; Gugliotta, Luigi; Bonini, Alessandro; Visani, Giuseppe; Skert, Cristina; Bergonzi, Cesare; Roccaro, Aldo Maria; Filí, Carla; Baccarani, Michele; Russo, Domenico.

In: British Journal of Haematology, Vol. 136, No. 1, 01.2007, p. 87-95.

Research output: Contribution to journalArticle

Malagola, M, Damiani, D, Martinelli, G, Michelutti, A, Cesana, B, Vivo, AD, Piccaluga, PP, Ottaviani, E, Candoni, A, Geromin, A, Tiribelli, M, Fanin, R, Testoni, N, Lauria, F, Bocchia, M, Gobbi, M, Pierri, I, Zaccaria, A, Zuffa, E, Mazza, P, Priccolo, G, Gugliotta, L, Bonini, A, Visani, G, Skert, C, Bergonzi, C, Roccaro, AM, Filí, C, Baccarani, M & Russo, D 2007, 'Case-control study of multidrug resistance phenotype and response to induction treatment including or not fludarabine in newly diagnosed acute myeloid leukaemia patients', British Journal of Haematology, vol. 136, no. 1, pp. 87-95. https://doi.org/10.1111/j.1365-2141.2006.06390.x
Malagola, Michele ; Damiani, Daniela ; Martinelli, Giovanni ; Michelutti, Angela ; Cesana, Bruno ; Vivo, Antonio De ; Piccaluga, Pier Paolo ; Ottaviani, Emanuela ; Candoni, Anna ; Geromin, Antonella ; Tiribelli, Mario ; Fanin, Renato ; Testoni, Nicoletta ; Lauria, Francesco ; Bocchia, Monica ; Gobbi, Marco ; Pierri, Ivana ; Zaccaria, Alfonso ; Zuffa, Eliana ; Mazza, Patrizio ; Priccolo, Giancarla ; Gugliotta, Luigi ; Bonini, Alessandro ; Visani, Giuseppe ; Skert, Cristina ; Bergonzi, Cesare ; Roccaro, Aldo Maria ; Filí, Carla ; Baccarani, Michele ; Russo, Domenico. / Case-control study of multidrug resistance phenotype and response to induction treatment including or not fludarabine in newly diagnosed acute myeloid leukaemia patients. In: British Journal of Haematology. 2007 ; Vol. 136, No. 1. pp. 87-95.
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AU - Cesana, Bruno

AU - Vivo, Antonio De

AU - Piccaluga, Pier Paolo

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AU - Candoni, Anna

AU - Geromin, Antonella

AU - Tiribelli, Mario

AU - Fanin, Renato

AU - Testoni, Nicoletta

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AU - Bocchia, Monica

AU - Gobbi, Marco

AU - Pierri, Ivana

AU - Zaccaria, Alfonso

AU - Zuffa, Eliana

AU - Mazza, Patrizio

AU - Priccolo, Giancarla

AU - Gugliotta, Luigi

AU - Bonini, Alessandro

AU - Visani, Giuseppe

AU - Skert, Cristina

AU - Bergonzi, Cesare

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