The mutations of NPM1 and FLT3-ITD represent the most frequent genetic aberration in acute myeloid leukemia. Indeed, the presence of an NPM1 mutation reduces the negative prognostic impact of FLT3-ITD in patients treated with conventional “3+7” induction. However, little information is available on their prognostic role with intensified regimens. Here, we investigated the efficacy of a fludarabine, high-dose cytarabine and idarubicin induction (FLAI) in 149 consecutive fit AML patients (median age 52) carrying the NPM1 and/or FLT3-ITD mutation, treated from 2008 to 2018. One-hundred-and-twenty-nine patients achieved CR (86.6%). After a median follow up of 68 months, 3-year overall survival was 58.6%. Multivariate analysis disclosed that both NPM1mut (p < 0.05) and ELN 2017 risk score (p < 0.05) were significant predictors of survival. NPM1-mutated patients had a favorable outcome, with no significant differences between patients with or without concomitant FLT3-ITD (p = 0.372), irrespective of FLT3-ITD allelic burden. Moreover, in landmark analysis, performing allogeneic transplantation (HSCT) in first CR proved to be beneficial only in ELN 2017 high-risk patients. Our data indicate that FLAI exerts a strong anti-leukemic effect in younger AML patients with NPM1mut and question the role of HSCT in 1st CR in NPM1mut patients with concomitant FLT3-ITD.

Fludarabine, high-dose cytarabine and idarubicin-based induction may overcome the negative prognostic impact of flt3-itd in npm1 mutated aml, irrespectively of flt3-itd allelic Burden / Minetto, P.; Candoni, A.; Guolo, F.; Clavio, M.; Zannier, M. E.; Miglino, M.; Dubbini, M. V.; Carminati, E.; Sicuranza, A.; Ciofini, S.; Colombo, N.; Pugliese, G.; Marcolin, R.; Santoni, A.; Ballerini, F.; Lanino, L.; Cea, M.; Gobbi, M.; Bocchia, M.; Fanin, R.; Lemoli, R. M.. - In: CANCERS. - ISSN 2072-6694. - 13:1(2021), pp. 1-13. [10.3390/cancers13010034]

Fludarabine, high-dose cytarabine and idarubicin-based induction may overcome the negative prognostic impact of flt3-itd in npm1 mutated aml, irrespectively of flt3-itd allelic Burden

Candoni A.;
2021

Abstract

The mutations of NPM1 and FLT3-ITD represent the most frequent genetic aberration in acute myeloid leukemia. Indeed, the presence of an NPM1 mutation reduces the negative prognostic impact of FLT3-ITD in patients treated with conventional “3+7” induction. However, little information is available on their prognostic role with intensified regimens. Here, we investigated the efficacy of a fludarabine, high-dose cytarabine and idarubicin induction (FLAI) in 149 consecutive fit AML patients (median age 52) carrying the NPM1 and/or FLT3-ITD mutation, treated from 2008 to 2018. One-hundred-and-twenty-nine patients achieved CR (86.6%). After a median follow up of 68 months, 3-year overall survival was 58.6%. Multivariate analysis disclosed that both NPM1mut (p < 0.05) and ELN 2017 risk score (p < 0.05) were significant predictors of survival. NPM1-mutated patients had a favorable outcome, with no significant differences between patients with or without concomitant FLT3-ITD (p = 0.372), irrespective of FLT3-ITD allelic burden. Moreover, in landmark analysis, performing allogeneic transplantation (HSCT) in first CR proved to be beneficial only in ELN 2017 high-risk patients. Our data indicate that FLAI exerts a strong anti-leukemic effect in younger AML patients with NPM1mut and question the role of HSCT in 1st CR in NPM1mut patients with concomitant FLT3-ITD.
2021
13
1
1
13
Fludarabine, high-dose cytarabine and idarubicin-based induction may overcome the negative prognostic impact of flt3-itd in npm1 mutated aml, irrespectively of flt3-itd allelic Burden / Minetto, P.; Candoni, A.; Guolo, F.; Clavio, M.; Zannier, M. E.; Miglino, M.; Dubbini, M. V.; Carminati, E.; Sicuranza, A.; Ciofini, S.; Colombo, N.; Pugliese, G.; Marcolin, R.; Santoni, A.; Ballerini, F.; Lanino, L.; Cea, M.; Gobbi, M.; Bocchia, M.; Fanin, R.; Lemoli, R. M.. - In: CANCERS. - ISSN 2072-6694. - 13:1(2021), pp. 1-13. [10.3390/cancers13010034]
Minetto, P.; Candoni, A.; Guolo, F.; Clavio, M.; Zannier, M. E.; Miglino, M.; Dubbini, M. V.; Carminati, E.; Sicuranza, A.; Ciofini, S.; Colombo, N.; Pugliese, G.; Marcolin, R.; Santoni, A.; Ballerini, F.; Lanino, L.; Cea, M.; Gobbi, M.; Bocchia, M.; Fanin, R.; Lemoli, R. M.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1294048
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