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  • Angenendt, LinusUniv Hosp Munster, Munster, Germany,University Hospital Münster (author)

Chromosomal Abnormalities and Prognosis in NPM1-Mutated Acute Myeloid Leukemia : A Pooled Analysis of Individual Patient Data From Nine International Cohorts

  • Article/chapterEnglish2019

Publisher, publication year, extent ...

  • AMER SOC CLINICAL ONCOLOGY,2019
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-396959
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-396959URI
  • https://doi.org/10.1200/JCO.19.00416DOI
  • https://lup.lub.lu.se/record/b6adf402-6bf6-45fd-a4a9-5adc6d5c71c9URI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:142169620URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • PURPOSE: Nucleophosmin 1 (NPM1) mutations are associated with a favorable prognosis in acute myeloid leukemia (AML) when an internal tandem duplication (ITD) in the fms-related tyrosine kinase 3 gene (FLT3) is absent (FLT3-ITDneg) or present with a low allelic ratio (FLT3-ITDlow). The 2017 European LeukemiaNet guidelines assume this is true regardless of accompanying cytogenetic abnormalities. We investigated the validity of this assumption.METHODS: We analyzed associations between karyotype and outcome in intensively treated patients with NPM1(mut)/FLT3-ITDneg/low AML who were prospectively enrolled in registry databases from nine international study groups or treatment centers.RESULTS: Among 2,426 patients with NPM1(mut)/FLT3-ITDneg/low AML, 2,000 (82.4%) had a normal and 426 (17.6%) had an abnormal karyotype, including 329 patients (13.6%) with intermediate and 83 patients (3.4%) with adverse-risk chromosomal abnormalities. In patients with NPM1(mut)/FLT3-ITDneg/low AML, adverse cytogenetics were associated with lower complete remission rates (87.7%, 86.0%, and 66.3% for normal, aberrant intermediate, and adverse karyotype, respectively; P < .001), inferior 5-year overall (52.4%, 44.8%, 19.5%, respectively; P < .001) and event-free survival (40.6%, 36.0%, 18.1%, respectively; P < .001), and a higher 5-year cumulative incidence of relapse (43.6%, 44.2%, 51.9%, respectively; P = .0012). These associations remained in multivariable mixed-effects regression analyses adjusted for known clinicopathologic risk factors (P < .001 for all end points). In patients with adverse-risk chromosomal aberrations, we found no significant influence of the NPM1 mutational status on outcome.CONCLUSION: Karyotype abnormalities are significantly associated with outcome in NPM1(mut)/FLT3-ITDneg/low AML. When adverse-risk cytogenetics are present, patients with NPM1(mut) share the same unfavorable prognosis as patients with NPM1 wild type and should be classified and treated accordingly. Thus, cytogenetic risk predominates over molecular risk in NPM1(mut)/FLT3-ITDneg/low AML.

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  • Röllig, ChristophTech Univ Dresden, Univ Hosp, Dresden, Germany,University Clinic Carl Gustav Carus at the TU Dresden (author)
  • Montesinos, PauHosp Univ & Politec La Fe, Valencia, Spain;Ctr Invest Biomed Red Canc, Madrid, Spain,University and Polytechnic Hospital la Fe (author)
  • Martinez-Cuadron, DavidHosp Univ & Politec La Fe, Valencia, Spain;Ctr Invest Biomed Red Canc, Madrid, Spain,University and Polytechnic Hospital la Fe (author)
  • Barragan, EvaHosp Univ & Politec La Fe, Valencia, Spain;Ctr Invest Biomed Red Canc, Madrid, Spain,University and Polytechnic Hospital la Fe (author)
  • Garcia, RaimundoGen Hosp Castellon, Castellon de La Plana, Spain,General Hospital Castellón (author)
  • Botella, CarmenHosp Gen Alicante, Alicante, Spain,Alicante University General Hospital (author)
  • Martinez, PilarHosp 12 Octubre, Madrid, Spain,12 de Octubre University Hospital (author)
  • Ravandi, FarhadUniv Texas MD Anderson Canc Ctr, Houston, TX 77030 USA,University of Texas (author)
  • Kadia, TapanUniv Texas MD Anderson Canc Ctr, Houston, TX 77030 USA,University of Texas (author)
  • Kantarjian, Hagop M.Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA,University of Texas (author)
  • Cortes, JorgeUniv Texas MD Anderson Canc Ctr, Houston, TX 77030 USA,University of Texas (author)
  • Juliusson, GunnarLund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)stem-gju (author)
  • Lazarevic, VladimirLund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)med-lzv (author)
  • Höglund, MartinUppsala universitet,Hematologi(Swepub:uu)martinhl (author)
  • Lehmann, SörenKarolinska Institutet,Uppsala universitet,Hematologi(Swepub:uu)sorle534 (author)
  • Recher, ChristianCHU Toulouse, Toulouse, France,Toulouse University Hospital (author)
  • Pigneux, ArnaudCHU Bordeaux, Hop Haut Leveque, Bordeaux, France,Hopital Haut-Leveque C.H.U de Bordeaux (author)
  • Bertoli, SarahCHU Toulouse, Toulouse, France,Toulouse University Hospital (author)
  • Dumas, Pierre-YvesCHU Bordeaux, Hop Haut Leveque, Bordeaux, France,Hopital Haut-Leveque C.H.U de Bordeaux (author)
  • Dombret, HerveParis Diderot Univ, Paris, France,Paris Diderot University (author)
  • Preudhomme, ClaudeInst Natl Sante & Rech Med Lille, Lille, France,Institut Gustave Roussy (author)
  • Micol, Jean-BaptisteParis Saclay Univ, Gustave Roussy, Villejuif, France,University of Paris-Saclay (author)
  • Terre, ChristineCtr Transfus Sanguine, Le Chesnay, France,Centre de Transfusion Sanguine (author)
  • Racil, ZdenekMasaryk Univ, Univ Hosp Brno, Brno, Czech Republic,University Hospital Brno (author)
  • Novak, JanCharles Univ Prague, Univ Hosp Kralovske Vinohrady, Fac Med 3, Prague, Czech Republic,University Hospital Kralovske Vinohrady (author)
  • Zak, PavelCharles Univ Prague, Univ Hosp Hradec Kralove, Hradec Kralove, Czech Republic,University Hospital Hradec Kralove (author)
  • Wei, Andrew H.Monash Univ, Alfred Hosp, Melbourne, Vic, Australia,Monash University (author)
  • Tiong, Ing S.Monash Univ, Alfred Hosp, Melbourne, Vic, Australia,Monash University (author)
  • Wall, MeaghanSt Vincents Hosp, Melbourne, Vic, Australia,St. Vincent's Hospital, Melbourne (author)
  • Estey, ElihuUniv Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA,University of Washington,University Hospital Münster (author)
  • Shaw, CaroleUniv Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA,University of Washington (author)
  • Exeler, RitaUniv Munster, Munster, Germany,University of Münster (author)
  • Wagenführ, LisaTech Univ Dresden, Univ Hosp, Dresden, Germany,Medizinsche Klinik und Poliklinik I, Dresden (author)
  • Stölzel, FriedrichTech Univ Dresden, Univ Hosp, Dresden, Germany,Medizinsche Klinik und Poliklinik I, Dresden (author)
  • Thiede, ChristianTech Univ Dresden, Univ Hosp, Dresden, Germany,Medizinsche Klinik und Poliklinik I, Dresden (author)
  • Stelljes, MatthiasUniv Hosp Munster, Munster, Germany,University Hospital Münster (author)
  • Lenz, GeorgUniv Hosp Munster, Munster, Germany,University Hospital Münster (author)
  • Mikesch, Jan-HenrikUniv Hosp Munster, Munster, Germany,University Hospital Münster (author)
  • Serve, HubertUniv Hosp Frankfurt, Frankfurt, Germany,University Hospital Frankfurt (author)
  • Ehninger, GerhardTech Univ Dresden, Univ Hosp, Dresden, Germany,Medizinsche Klinik und Poliklinik I, Dresden (author)
  • Berdel, Wolfgang E.Univ Hosp Munster, Munster, Germany (author)
  • Kramer, MichaelTech Univ Dresden, Univ Hosp, Dresden, Germany,Medizinsche Klinik und Poliklinik I, Dresden (author)
  • Krug, UtzKlinikum Leverkusen, Leverkusen, Germany,Hospital Leverkusen (author)
  • Schliemann, ChristophUniv Hosp Munster, Munster, Germany,University Hospital Münster (author)
  • Univ Hosp Munster, Munster, GermanyUniversity Hospital Münster (creator_code:org_t)

Related titles

  • In:Journal of Clinical Oncology: AMER SOC CLINICAL ONCOLOGY37:29, s. 2632-26420732-183X1527-7755

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