Prognostic Relevance of <i>NPM1</i> and <i>FLT3</i> Mutations in Acute Myeloid Leukaemia, Longterm Follow-Up—A Single Center Experience
The prognosis of acute myeloid leukemia depends on genetic aberrations, particularly <i>NPM1</i> and <i>FLT3</i>-ITD mutations. The targeted drugs’ availability has renewed interest in <i>FLT3</i> mutations, but the impact of these genetic alterations using these...
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| Language: | English |
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MDPI AG
2022-09-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/19/4716 |
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| author | Erika Borlenghi Chiara Cattaneo Diego Bertoli Elisa Cerqui Silvana Archetti Angela Passi Margherita Oberti Tatiana Zollner Carlotta Giupponi Chiara Pagani Nicola Bianchetti Chiara Bottelli Samuele Bagnasco Margherita Sciumè Alessandra Tucci Giuseppe Rossi |
| author_facet | Erika Borlenghi Chiara Cattaneo Diego Bertoli Elisa Cerqui Silvana Archetti Angela Passi Margherita Oberti Tatiana Zollner Carlotta Giupponi Chiara Pagani Nicola Bianchetti Chiara Bottelli Samuele Bagnasco Margherita Sciumè Alessandra Tucci Giuseppe Rossi |
| author_sort | Erika Borlenghi |
| collection | DOAJ |
| description | The prognosis of acute myeloid leukemia depends on genetic aberrations, particularly <i>NPM1</i> and <i>FLT3</i>-ITD mutations. The targeted drugs’ availability has renewed interest in <i>FLT3</i> mutations, but the impact of these genetic alterations using these treatments is yet to be confirmed. Our objective was to evaluate the results obtained with the intensified NILG-AML 01/00 protocol (ClinicalTrials.gov Identifier: NCT 00400673) in 171 unselected patients (median age, 54.5 years, range 15–74) carrying the <i>FLT3</i> (ITD or TKD) and/or <i>NPM1</i> mutations. The CR rate and 5-y survival were 88.3% and 58% +/− 4, respectively, significantly higher in the <i>NPM1</i>-mutated (CR 93.9%, <i>p</i>: 0.0001; survival 71% +/− 6, <i>p</i>: 0.0017, respectively). In isolated ITD patients, the CR was lower (66.7%, <i>p</i>: 0.0009), and the 3 years-relapse-free survival worse (24%, <i>p</i>: <0.0002). The presence of ITD, irrespective of the allelic ratio, or TKD mutation, did not significantly affect the survival or relapse-free survival among the <i>NPM1</i>-co-mutated patients. Our data indicate that a high dose of ARAC plus idarubicin consolidation exerts a strong anti-leukemic effect in <i>NPM1</i>-mutated patients both with the <i>FLT3</i> wild-type and mutated AML, while in the <i>NPM1</i> wild-type and <i>FLT3</i>-mutated, the therapeutic effect remains unsatisfactory. New strategies incorporating target therapy with second-generation inhibitors will improve these results and their addition to this aggressive chemotherapeutic program merits testing. |
| first_indexed | 2024-03-09T21:57:21Z |
| format | Article |
| id | doaj.art-1ba1b960839341c28cc1fe0ad33cc37c |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T21:57:21Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-1ba1b960839341c28cc1fe0ad33cc37c2023-11-23T19:55:27ZengMDPI AGCancers2072-66942022-09-011419471610.3390/cancers14194716Prognostic Relevance of <i>NPM1</i> and <i>FLT3</i> Mutations in Acute Myeloid Leukaemia, Longterm Follow-Up—A Single Center ExperienceErika Borlenghi0Chiara Cattaneo1Diego Bertoli2Elisa Cerqui3Silvana Archetti4Angela Passi5Margherita Oberti6Tatiana Zollner7Carlotta Giupponi8Chiara Pagani9Nicola Bianchetti10Chiara Bottelli11Samuele Bagnasco12Margherita Sciumè13Alessandra Tucci14Giuseppe Rossi15Department of Haematology, ASST Spedali Civili, 25100 Brescia, ItalyDepartment of Haematology, ASST Spedali Civili, 25100 Brescia, ItalyDiagnostic Department, Clinical Chemistry Laboratory, ASST Spedali Civili, 25100 Brescia, ItalyDepartment of Haematology, ASST Spedali Civili, 25100 Brescia, ItalyDiagnostic Department, Clinical Chemistry Laboratory, ASST Spedali Civili, 25100 Brescia, ItalyDepartment of Haematology, ASST Spedali Civili, 25100 Brescia, ItalyDepartment of Haematology, ASST Spedali Civili, 25100 Brescia, ItalyDepartment of Haematology, ASST Spedali Civili, 25100 Brescia, ItalyDepartment of Haematology, ASST Spedali Civili, 25100 Brescia, ItalyDepartment of Haematology, ASST Spedali Civili, 25100 Brescia, ItalyDepartment of Haematology, ASST Spedali Civili, 25100 Brescia, ItalyDepartment of Haematology, ASST Spedali Civili, 25100 Brescia, ItalyDepartment of Haematology, ASST Spedali Civili, 25100 Brescia, ItalyDepartment of Haematology, ASST Spedali Civili, 25100 Brescia, ItalyDepartment of Haematology, ASST Spedali Civili, 25100 Brescia, ItalyDepartment of Haematology, ASST Spedali Civili, 25100 Brescia, ItalyThe prognosis of acute myeloid leukemia depends on genetic aberrations, particularly <i>NPM1</i> and <i>FLT3</i>-ITD mutations. The targeted drugs’ availability has renewed interest in <i>FLT3</i> mutations, but the impact of these genetic alterations using these treatments is yet to be confirmed. Our objective was to evaluate the results obtained with the intensified NILG-AML 01/00 protocol (ClinicalTrials.gov Identifier: NCT 00400673) in 171 unselected patients (median age, 54.5 years, range 15–74) carrying the <i>FLT3</i> (ITD or TKD) and/or <i>NPM1</i> mutations. The CR rate and 5-y survival were 88.3% and 58% +/− 4, respectively, significantly higher in the <i>NPM1</i>-mutated (CR 93.9%, <i>p</i>: 0.0001; survival 71% +/− 6, <i>p</i>: 0.0017, respectively). In isolated ITD patients, the CR was lower (66.7%, <i>p</i>: 0.0009), and the 3 years-relapse-free survival worse (24%, <i>p</i>: <0.0002). The presence of ITD, irrespective of the allelic ratio, or TKD mutation, did not significantly affect the survival or relapse-free survival among the <i>NPM1</i>-co-mutated patients. Our data indicate that a high dose of ARAC plus idarubicin consolidation exerts a strong anti-leukemic effect in <i>NPM1</i>-mutated patients both with the <i>FLT3</i> wild-type and mutated AML, while in the <i>NPM1</i> wild-type and <i>FLT3</i>-mutated, the therapeutic effect remains unsatisfactory. New strategies incorporating target therapy with second-generation inhibitors will improve these results and their addition to this aggressive chemotherapeutic program merits testing.https://www.mdpi.com/2072-6694/14/19/4716acute myeloid leukaemiahigh dose cytarabine (HD-ARAC)idarubicin<i>FLT3</i> mutation<i>NPM1</i> mutation |
| spellingShingle | Erika Borlenghi Chiara Cattaneo Diego Bertoli Elisa Cerqui Silvana Archetti Angela Passi Margherita Oberti Tatiana Zollner Carlotta Giupponi Chiara Pagani Nicola Bianchetti Chiara Bottelli Samuele Bagnasco Margherita Sciumè Alessandra Tucci Giuseppe Rossi Prognostic Relevance of <i>NPM1</i> and <i>FLT3</i> Mutations in Acute Myeloid Leukaemia, Longterm Follow-Up—A Single Center Experience Cancers acute myeloid leukaemia high dose cytarabine (HD-ARAC) idarubicin <i>FLT3</i> mutation <i>NPM1</i> mutation |
| title | Prognostic Relevance of <i>NPM1</i> and <i>FLT3</i> Mutations in Acute Myeloid Leukaemia, Longterm Follow-Up—A Single Center Experience |
| title_full | Prognostic Relevance of <i>NPM1</i> and <i>FLT3</i> Mutations in Acute Myeloid Leukaemia, Longterm Follow-Up—A Single Center Experience |
| title_fullStr | Prognostic Relevance of <i>NPM1</i> and <i>FLT3</i> Mutations in Acute Myeloid Leukaemia, Longterm Follow-Up—A Single Center Experience |
| title_full_unstemmed | Prognostic Relevance of <i>NPM1</i> and <i>FLT3</i> Mutations in Acute Myeloid Leukaemia, Longterm Follow-Up—A Single Center Experience |
| title_short | Prognostic Relevance of <i>NPM1</i> and <i>FLT3</i> Mutations in Acute Myeloid Leukaemia, Longterm Follow-Up—A Single Center Experience |
| title_sort | prognostic relevance of i npm1 i and i flt3 i mutations in acute myeloid leukaemia longterm follow up a single center experience |
| topic | acute myeloid leukaemia high dose cytarabine (HD-ARAC) idarubicin <i>FLT3</i> mutation <i>NPM1</i> mutation |
| url | https://www.mdpi.com/2072-6694/14/19/4716 |
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