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
The mutations of and -ITD represent the most frequent genetic aberration in acute myeloid leukemia. Indeed, the presence of an mutation reduces the negative prognostic impact of -ITD in patients treated with conventional "3+7" induction. However, little information is available on their pr...
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| Veröffentlicht in: | Cancers 2020-12, Vol.13 (1), p.34 |
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| creator | Minetto, Paola Candoni, Anna Guolo, Fabio Clavio, Marino Zannier, Maria Elena Miglino, Maurizio Dubbini, Maria Vittoria Carminati, Enrico Sicuranza, Anna Ciofini, Sara Colombo, Nicoletta Pugliese, Girolamo Marcolin, Riccardo Santoni, Adele Ballerini, Filippo Lanino, Luca Cea, Michele Gobbi, Marco Bocchia, Monica Fanin, Renato Lemoli, Roberto Massimo |
| description | The mutations of
and
-ITD represent the most frequent genetic aberration in acute myeloid leukemia. Indeed, the presence of an
mutation reduces the negative prognostic impact of
-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
and/or
-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
mut (
< 0.05) and ELN 2017 risk score (
< 0.05) were significant predictors of survival.
-mutated patients had a favorable outcome, with no significant differences between patients with or without concomitant
-ITD (
= 0.372), irrespective of
-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
mut and question the role of HSCT in 1st CR in
mut patients with concomitant
-ITD. |
| doi_str_mv | 10.3390/cancers13010034 |
| format | Article |
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and
-ITD represent the most frequent genetic aberration in acute myeloid leukemia. Indeed, the presence of an
mutation reduces the negative prognostic impact of
-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
and/or
-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
mut (
< 0.05) and ELN 2017 risk score (
< 0.05) were significant predictors of survival.
-mutated patients had a favorable outcome, with no significant differences between patients with or without concomitant
-ITD (
= 0.372), irrespective of
-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
mut and question the role of HSCT in 1st CR in
mut patients with concomitant
-ITD.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers13010034</identifier><identifier>PMID: 33374216</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Acute myeloid leukemia ; Bone marrow ; Chemotherapy ; Cytarabine ; Fludarabine ; Hematology ; Leukemia ; Linux ; Medical prognosis ; Mortality ; Multivariate analysis ; Mutation ; Myeloid leukemia ; Risk groups ; Statistical analysis ; Stem cell transplantation ; Survival ; Survival analysis ; Transplants & implants</subject><ispartof>Cancers, 2020-12, Vol.13 (1), p.34</ispartof><rights>2021. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-345440416d354d6e217fe1bc1aa95e5adac22a2efc48b9d0d6c56f8cc0d77b4e3</citedby><cites>FETCH-LOGICAL-c421t-345440416d354d6e217fe1bc1aa95e5adac22a2efc48b9d0d6c56f8cc0d77b4e3</cites><orcidid>0000-0003-0756-109X ; 0000-0003-4436-1310 ; 0000-0002-1530-6729 ; 0000-0003-2404-8829 ; 0000-0001-6094-4351 ; 0000-0003-3166-6078 ; 0000-0003-3538-3913</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796342/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796342/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33374216$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Minetto, Paola</creatorcontrib><creatorcontrib>Candoni, Anna</creatorcontrib><creatorcontrib>Guolo, Fabio</creatorcontrib><creatorcontrib>Clavio, Marino</creatorcontrib><creatorcontrib>Zannier, Maria Elena</creatorcontrib><creatorcontrib>Miglino, Maurizio</creatorcontrib><creatorcontrib>Dubbini, Maria Vittoria</creatorcontrib><creatorcontrib>Carminati, Enrico</creatorcontrib><creatorcontrib>Sicuranza, Anna</creatorcontrib><creatorcontrib>Ciofini, Sara</creatorcontrib><creatorcontrib>Colombo, Nicoletta</creatorcontrib><creatorcontrib>Pugliese, Girolamo</creatorcontrib><creatorcontrib>Marcolin, Riccardo</creatorcontrib><creatorcontrib>Santoni, Adele</creatorcontrib><creatorcontrib>Ballerini, Filippo</creatorcontrib><creatorcontrib>Lanino, Luca</creatorcontrib><creatorcontrib>Cea, Michele</creatorcontrib><creatorcontrib>Gobbi, Marco</creatorcontrib><creatorcontrib>Bocchia, Monica</creatorcontrib><creatorcontrib>Fanin, Renato</creatorcontrib><creatorcontrib>Lemoli, Roberto Massimo</creatorcontrib><title>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</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>The mutations of
and
-ITD represent the most frequent genetic aberration in acute myeloid leukemia. Indeed, the presence of an
mutation reduces the negative prognostic impact of
-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
and/or
-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
mut (
< 0.05) and ELN 2017 risk score (
< 0.05) were significant predictors of survival.
-mutated patients had a favorable outcome, with no significant differences between patients with or without concomitant
-ITD (
= 0.372), irrespective of
-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
mut and question the role of HSCT in 1st CR in
mut patients with concomitant
-ITD.</description><subject>Acute myeloid leukemia</subject><subject>Bone marrow</subject><subject>Chemotherapy</subject><subject>Cytarabine</subject><subject>Fludarabine</subject><subject>Hematology</subject><subject>Leukemia</subject><subject>Linux</subject><subject>Medical prognosis</subject><subject>Mortality</subject><subject>Multivariate analysis</subject><subject>Mutation</subject><subject>Myeloid leukemia</subject><subject>Risk groups</subject><subject>Statistical analysis</subject><subject>Stem cell transplantation</subject><subject>Survival</subject><subject>Survival analysis</subject><subject>Transplants & 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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</title><author>Minetto, Paola ; Candoni, Anna ; Guolo, Fabio ; Clavio, Marino ; Zannier, Maria Elena ; Miglino, Maurizio ; Dubbini, Maria Vittoria ; Carminati, Enrico ; Sicuranza, Anna ; Ciofini, Sara ; Colombo, Nicoletta ; Pugliese, Girolamo ; Marcolin, Riccardo ; Santoni, Adele ; Ballerini, Filippo ; Lanino, Luca ; Cea, Michele ; Gobbi, Marco ; Bocchia, Monica ; Fanin, Renato ; Lemoli, Roberto Massimo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-345440416d354d6e217fe1bc1aa95e5adac22a2efc48b9d0d6c56f8cc0d77b4e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Acute myeloid leukemia</topic><topic>Bone marrow</topic><topic>Chemotherapy</topic><topic>Cytarabine</topic><topic>Fludarabine</topic><topic>Hematology</topic><topic>Leukemia</topic><topic>Linux</topic><topic>Medical prognosis</topic><topic>Mortality</topic><topic>Multivariate analysis</topic><topic>Mutation</topic><topic>Myeloid leukemia</topic><topic>Risk groups</topic><topic>Statistical analysis</topic><topic>Stem cell transplantation</topic><topic>Survival</topic><topic>Survival analysis</topic><topic>Transplants & implants</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Minetto, Paola</creatorcontrib><creatorcontrib>Candoni, Anna</creatorcontrib><creatorcontrib>Guolo, Fabio</creatorcontrib><creatorcontrib>Clavio, Marino</creatorcontrib><creatorcontrib>Zannier, Maria Elena</creatorcontrib><creatorcontrib>Miglino, Maurizio</creatorcontrib><creatorcontrib>Dubbini, Maria Vittoria</creatorcontrib><creatorcontrib>Carminati, Enrico</creatorcontrib><creatorcontrib>Sicuranza, 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Marco</au><au>Bocchia, Monica</au><au>Fanin, Renato</au><au>Lemoli, Roberto Massimo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2020-12-24</date><risdate>2020</risdate><volume>13</volume><issue>1</issue><spage>34</spage><pages>34-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>The mutations of
and
-ITD represent the most frequent genetic aberration in acute myeloid leukemia. Indeed, the presence of an
mutation reduces the negative prognostic impact of
-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
and/or
-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
mut (
< 0.05) and ELN 2017 risk score (
< 0.05) were significant predictors of survival.
-mutated patients had a favorable outcome, with no significant differences between patients with or without concomitant
-ITD (
= 0.372), irrespective of
-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
mut and question the role of HSCT in 1st CR in
mut patients with concomitant
-ITD.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>33374216</pmid><doi>10.3390/cancers13010034</doi><orcidid>https://orcid.org/0000-0003-0756-109X</orcidid><orcidid>https://orcid.org/0000-0003-4436-1310</orcidid><orcidid>https://orcid.org/0000-0002-1530-6729</orcidid><orcidid>https://orcid.org/0000-0003-2404-8829</orcidid><orcidid>https://orcid.org/0000-0001-6094-4351</orcidid><orcidid>https://orcid.org/0000-0003-3166-6078</orcidid><orcidid>https://orcid.org/0000-0003-3538-3913</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2072-6694 |
| ispartof | Cancers, 2020-12, Vol.13 (1), p.34 |
| issn | 2072-6694 2072-6694 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7796342 |
| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; MDPI - Multidisciplinary Digital Publishing Institute; PubMed Central |
| subjects | Acute myeloid leukemia Bone marrow Chemotherapy Cytarabine Fludarabine Hematology Leukemia Linux Medical prognosis Mortality Multivariate analysis Mutation Myeloid leukemia Risk groups Statistical analysis Stem cell transplantation Survival Survival analysis Transplants & implants |
| title | 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 |
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