Combination of FLT3-ITD Allelic Ratio, NPM1 Mutation, and Immunophenotypic Markers to Modulate Outcome Prediction in Patients with Normal Karyotype Acute Myelogenous Leukemia Undergoing Hematopoietic Stem Cell Transplantation
•NPM1 mutation and FLT3-ITD allelic ratio are important clinical predictors.•HSCT confers a better outcome in patients with genotype NPM1wt/FLT3-ITDneg/low.•Immunophenotypic markers may help further refine genetic subgroups for HSCT.•Lack of CD13 expression ameliorates the benefit associated with fa...
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| Veröffentlicht in: | Biology of blood and marrow transplantation 2020-11, Vol.26 (11), p.1995-2000 |
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| container_issue | 11 |
| container_start_page | 1995 |
| container_title | Biology of blood and marrow transplantation |
| container_volume | 26 |
| creator | Jiang, Gina Capo-Chichi, Jose-Mario Liu, Aijun Atenafu, Eshetu G. Kumar, Rajat Minden, Mark D. Chang, Hong |
| description | •NPM1 mutation and FLT3-ITD allelic ratio are important clinical predictors.•HSCT confers a better outcome in patients with genotype NPM1wt/FLT3-ITDneg/low.•Immunophenotypic markers may help further refine genetic subgroups for HSCT.•Lack of CD13 expression ameliorates the benefit associated with favorable genotype.
NPM1 mutation status and the allelic ratio (AR) of FLT3-internal tandem duplication (FLT3-ITD) are routinely tested for disease risk stratification in patients with normal karyotype (NK) acute myelogenous leukemia (AML); however, the predictive impact of immunophenotypic markers on different NPM1/FLT3 genotypes remains unclear. We performed a retrospective analysis of 423 patients with NK-AML subclassified into groups based on NPM1/FLT3 genotype. Allogeneic hematopoietic stem cell transplantation (HSCT) was performed in 124 of 423 patients (29%) and was significantly associated with longer event-free survival (EFS) and overall survival (OS), except for patients with the favorable genotype, defined as mutated NPM1 (NPM1mut) combined with normal FLT3 status (FLT3-ITDneg) or FLT3-ITD AR |
| doi_str_mv | 10.1016/j.bbmt.2020.07.017 |
| format | Article |
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NPM1 mutation status and the allelic ratio (AR) of FLT3-internal tandem duplication (FLT3-ITD) are routinely tested for disease risk stratification in patients with normal karyotype (NK) acute myelogenous leukemia (AML); however, the predictive impact of immunophenotypic markers on different NPM1/FLT3 genotypes remains unclear. We performed a retrospective analysis of 423 patients with NK-AML subclassified into groups based on NPM1/FLT3 genotype. Allogeneic hematopoietic stem cell transplantation (HSCT) was performed in 124 of 423 patients (29%) and was significantly associated with longer event-free survival (EFS) and overall survival (OS), except for patients with the favorable genotype, defined as mutated NPM1 (NPM1mut) combined with normal FLT3 status (FLT3-ITDneg) or FLT3-ITD AR <.5 (FLT3-ITDlow). A subset of AML patients bearing the favorable NPM1mut/FLT3-ITDneg/low genotype share similar outcomes with AML patients who have the intermediate FLT3/NPM1 genotype defined by normal NPM1 (NPM1wt) and FLT3-ITDneg/low. In these individuals, the lack of CD13 expression (CD13neg) was associated with shorter EFS (P = .041) and OS (P = .017). CD13neg was an independent predictor for shorter OS (hazard ratio, 1.985; P = .028).</description><identifier>ISSN: 1083-8791</identifier><identifier>EISSN: 1523-6536</identifier><identifier>DOI: 10.1016/j.bbmt.2020.07.017</identifier><identifier>PMID: 32712325</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>AML ; FLT3-ITD ; fms-Like Tyrosine Kinase 3 - genetics ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunophenotyping ; Karyotype ; Leukemia, Myeloid, Acute - genetics ; Leukemia, Myeloid, Acute - therapy ; Mutation ; NPM1 ; Nuclear Proteins - genetics ; Nucleophosmin ; Prognosis ; Retrospective Studies</subject><ispartof>Biology of blood and marrow transplantation, 2020-11, Vol.26 (11), p.1995-2000</ispartof><rights>2020 American Society for Transplantation and Cellular Therapy</rights><rights>Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c400t-b0d029a104bde7ee896860150a1c512ac1dd777b23c54b073605c0a5d495a4a03</citedby><cites>FETCH-LOGICAL-c400t-b0d029a104bde7ee896860150a1c512ac1dd777b23c54b073605c0a5d495a4a03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbmt.2020.07.017$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32712325$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jiang, Gina</creatorcontrib><creatorcontrib>Capo-Chichi, Jose-Mario</creatorcontrib><creatorcontrib>Liu, Aijun</creatorcontrib><creatorcontrib>Atenafu, Eshetu G.</creatorcontrib><creatorcontrib>Kumar, Rajat</creatorcontrib><creatorcontrib>Minden, Mark D.</creatorcontrib><creatorcontrib>Chang, Hong</creatorcontrib><title>Combination of FLT3-ITD Allelic Ratio, NPM1 Mutation, and Immunophenotypic Markers to Modulate Outcome Prediction in Patients with Normal Karyotype Acute Myelogenous Leukemia Undergoing Hematopoietic Stem Cell Transplantation</title><title>Biology of blood and marrow transplantation</title><addtitle>Biol Blood Marrow Transplant</addtitle><description>•NPM1 mutation and FLT3-ITD allelic ratio are important clinical predictors.•HSCT confers a better outcome in patients with genotype NPM1wt/FLT3-ITDneg/low.•Immunophenotypic markers may help further refine genetic subgroups for HSCT.•Lack of CD13 expression ameliorates the benefit associated with favorable genotype.
NPM1 mutation status and the allelic ratio (AR) of FLT3-internal tandem duplication (FLT3-ITD) are routinely tested for disease risk stratification in patients with normal karyotype (NK) acute myelogenous leukemia (AML); however, the predictive impact of immunophenotypic markers on different NPM1/FLT3 genotypes remains unclear. We performed a retrospective analysis of 423 patients with NK-AML subclassified into groups based on NPM1/FLT3 genotype. Allogeneic hematopoietic stem cell transplantation (HSCT) was performed in 124 of 423 patients (29%) and was significantly associated with longer event-free survival (EFS) and overall survival (OS), except for patients with the favorable genotype, defined as mutated NPM1 (NPM1mut) combined with normal FLT3 status (FLT3-ITDneg) or FLT3-ITD AR <.5 (FLT3-ITDlow). A subset of AML patients bearing the favorable NPM1mut/FLT3-ITDneg/low genotype share similar outcomes with AML patients who have the intermediate FLT3/NPM1 genotype defined by normal NPM1 (NPM1wt) and FLT3-ITDneg/low. In these individuals, the lack of CD13 expression (CD13neg) was associated with shorter EFS (P = .041) and OS (P = .017). CD13neg was an independent predictor for shorter OS (hazard ratio, 1.985; P = .028).</description><subject>AML</subject><subject>FLT3-ITD</subject><subject>fms-Like Tyrosine Kinase 3 - genetics</subject><subject>Hematopoietic Stem Cell Transplantation</subject><subject>Humans</subject><subject>Immunophenotyping</subject><subject>Karyotype</subject><subject>Leukemia, Myeloid, Acute - genetics</subject><subject>Leukemia, Myeloid, Acute - therapy</subject><subject>Mutation</subject><subject>NPM1</subject><subject>Nuclear Proteins - genetics</subject><subject>Nucleophosmin</subject><subject>Prognosis</subject><subject>Retrospective Studies</subject><issn>1083-8791</issn><issn>1523-6536</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc9uEzEQxlcIREvhBTggHzl0w9j7x1mJSxQojUjaCNKz5fVOUqdre7G9oDwub4LTFI6cPJK_-Wa--WXZWwoTCrT-sJ-0rYkTBgwmwCdA-bPsnFasyOuqqJ-nGqZFPuUNPctehbAHAF5Om5fZWcE4ZQWrzrPfc2dabWXUzhK3JVfLTZEvNp_IrO-x14p8O35dkpv1ipLVGB-Fl0TajiyMGa0b7tG6eBiSdCX9A_pAoiMr1429jEhux6icQbL22Gn1OEVbsk42aGMgv3S8JzfOG9mTr9Ifjk5IZmpMrasD9m6X3MdAljg-oNGS3NkO_c5puyPXaGR0g9MY0_DvEQ2ZY9-TjZc2DL20p2VfZy-2sg_45um9yO6uPm_m1_ny9stiPlvmqgSIeQsdsEZSKNsOOeK0qac10AokVRVlUtGu45y3rFBV2QIvaqgUyKorm0qWEoqL7P3Jd_Dux4ghCqODSgtJiymCYCXjiU3ZFEnKTlLlXQget2Lw2qT4goI4ohV7cUQrjmgFcJHQpqZ3T_5ja7D71_KXZRJ8PAkwpfyp0Yug0pVVOrxHFUXn9P_8_wDqObkM</recordid><startdate>202011</startdate><enddate>202011</enddate><creator>Jiang, Gina</creator><creator>Capo-Chichi, Jose-Mario</creator><creator>Liu, Aijun</creator><creator>Atenafu, Eshetu G.</creator><creator>Kumar, Rajat</creator><creator>Minden, Mark D.</creator><creator>Chang, Hong</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202011</creationdate><title>Combination of FLT3-ITD Allelic Ratio, NPM1 Mutation, and Immunophenotypic Markers to Modulate Outcome Prediction in Patients with Normal Karyotype Acute Myelogenous Leukemia Undergoing Hematopoietic Stem Cell Transplantation</title><author>Jiang, Gina ; Capo-Chichi, Jose-Mario ; Liu, Aijun ; Atenafu, Eshetu G. ; Kumar, Rajat ; Minden, Mark D. ; Chang, Hong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c400t-b0d029a104bde7ee896860150a1c512ac1dd777b23c54b073605c0a5d495a4a03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>AML</topic><topic>FLT3-ITD</topic><topic>fms-Like Tyrosine Kinase 3 - genetics</topic><topic>Hematopoietic Stem Cell Transplantation</topic><topic>Humans</topic><topic>Immunophenotyping</topic><topic>Karyotype</topic><topic>Leukemia, Myeloid, Acute - genetics</topic><topic>Leukemia, Myeloid, Acute - therapy</topic><topic>Mutation</topic><topic>NPM1</topic><topic>Nuclear Proteins - genetics</topic><topic>Nucleophosmin</topic><topic>Prognosis</topic><topic>Retrospective Studies</topic><toplevel>online_resources</toplevel><creatorcontrib>Jiang, Gina</creatorcontrib><creatorcontrib>Capo-Chichi, Jose-Mario</creatorcontrib><creatorcontrib>Liu, Aijun</creatorcontrib><creatorcontrib>Atenafu, Eshetu G.</creatorcontrib><creatorcontrib>Kumar, Rajat</creatorcontrib><creatorcontrib>Minden, Mark D.</creatorcontrib><creatorcontrib>Chang, Hong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biology of blood and marrow transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jiang, Gina</au><au>Capo-Chichi, Jose-Mario</au><au>Liu, Aijun</au><au>Atenafu, Eshetu G.</au><au>Kumar, Rajat</au><au>Minden, Mark D.</au><au>Chang, Hong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Combination of FLT3-ITD Allelic Ratio, NPM1 Mutation, and Immunophenotypic Markers to Modulate Outcome Prediction in Patients with Normal Karyotype Acute Myelogenous Leukemia Undergoing Hematopoietic Stem Cell Transplantation</atitle><jtitle>Biology of blood and marrow transplantation</jtitle><addtitle>Biol Blood Marrow Transplant</addtitle><date>2020-11</date><risdate>2020</risdate><volume>26</volume><issue>11</issue><spage>1995</spage><epage>2000</epage><pages>1995-2000</pages><issn>1083-8791</issn><eissn>1523-6536</eissn><abstract>•NPM1 mutation and FLT3-ITD allelic ratio are important clinical predictors.•HSCT confers a better outcome in patients with genotype NPM1wt/FLT3-ITDneg/low.•Immunophenotypic markers may help further refine genetic subgroups for HSCT.•Lack of CD13 expression ameliorates the benefit associated with favorable genotype.
NPM1 mutation status and the allelic ratio (AR) of FLT3-internal tandem duplication (FLT3-ITD) are routinely tested for disease risk stratification in patients with normal karyotype (NK) acute myelogenous leukemia (AML); however, the predictive impact of immunophenotypic markers on different NPM1/FLT3 genotypes remains unclear. We performed a retrospective analysis of 423 patients with NK-AML subclassified into groups based on NPM1/FLT3 genotype. Allogeneic hematopoietic stem cell transplantation (HSCT) was performed in 124 of 423 patients (29%) and was significantly associated with longer event-free survival (EFS) and overall survival (OS), except for patients with the favorable genotype, defined as mutated NPM1 (NPM1mut) combined with normal FLT3 status (FLT3-ITDneg) or FLT3-ITD AR <.5 (FLT3-ITDlow). A subset of AML patients bearing the favorable NPM1mut/FLT3-ITDneg/low genotype share similar outcomes with AML patients who have the intermediate FLT3/NPM1 genotype defined by normal NPM1 (NPM1wt) and FLT3-ITDneg/low. In these individuals, the lack of CD13 expression (CD13neg) was associated with shorter EFS (P = .041) and OS (P = .017). CD13neg was an independent predictor for shorter OS (hazard ratio, 1.985; P = .028).</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>32712325</pmid><doi>10.1016/j.bbmt.2020.07.017</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elsevier ScienceDirect Journals; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | AML FLT3-ITD fms-Like Tyrosine Kinase 3 - genetics Hematopoietic Stem Cell Transplantation Humans Immunophenotyping Karyotype Leukemia, Myeloid, Acute - genetics Leukemia, Myeloid, Acute - therapy Mutation NPM1 Nuclear Proteins - genetics Nucleophosmin Prognosis Retrospective Studies |
| title | Combination of FLT3-ITD Allelic Ratio, NPM1 Mutation, and Immunophenotypic Markers to Modulate Outcome Prediction in Patients with Normal Karyotype Acute Myelogenous Leukemia Undergoing Hematopoietic Stem Cell Transplantation |
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