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  • Schmid, Christoph (author)

Outcome and risk factor analysis of molecular subgroups in cytogenetically normal AML treated by allogeneic transplantation.

  • Article/chapterEnglish2015

Publisher, publication year, extent ...

  • American Society of Hematology,2015

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  • LIBRIS-ID:oai:lup.lub.lu.se:52d8bed0-a9a2-4d59-bdbf-64b4a7718625
  • https://lup.lub.lu.se/record/8042796URI
  • https://doi.org/10.1182/blood-2015-06-651562DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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

Notes

  • Patients with cytogenetically normal acute myeloid leukemia (CN-AML) can be subdivided by molecular mutations. However, data on the influence of combinations of different aberrations on outcome after allogeneic hematopoietic stem cell transplantation (HSCT) is limited. Therefore, we performed a retrospective registry analysis on 702 adults with CN-AML undergoing HSCT in first complete remission (CR). Patients were grouped according to presence or absence of NPM1 mutations (NPM1(mut)) and FLT3 internal tandem duplications (FLT3-ITD). Double negative patients were evaluated for mutations of the CCAAT/enhancer binding protein α gene (CEBPα). The influence of genotypes on relapse, non-relapse mortality, leukemia-free survival (LFS) and overall survival (OS), and a prognostic classification combining NPM1/FLT3-ITD profile and classical risk factors were calculated. 2y-OS from HSCT was 81±5% in NPM1(mut)/FLT3(wt) (n=68), 75±3% in NPM1(wt)/FLT3(wt) (n=290), 66±3% in NPM1(mut)/FLT3-ITD (n=269) and 54±7% in NPM1(wt)/FLT3-ITD (n=75; p=0.003). Analysis of CEBPα among patients with NPM1(wt)/FLT3(wt) revealed excellent results both in patients with CEBPα(mut) (n=13, 2y-OS:100%), and with a triple negative genotype (n=138, 2y-OS:77±3%). In a Cox-model of predefined factors, older age, presence of FLT3-ITD and >1 course of chemotherapy to reach CR were associated with inferior outcome. 2y-OS/LFS were 88±3%/79±4% in patients without any, 77±2%/73±3% with one, and 53±4%/50±4 with>=2 risk factors (p=0.002 for LFS, p=0.003 for OS). Hence, FLT3-ITD proofed to be the decisive molecular marker for outcome after HSCT for CN-AML in CR1, regardless of NPM1 mutational status, variations of transplant protocols, or development of GvHD. Age, FLT3-ITD and response to induction chemotherapy allow for a prognostic risk classification.

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  • Labopin, Myriam (author)
  • Socié, Gerard (author)
  • Daguindau, Etienne (author)
  • Volin, Liisa (author)
  • Huynh, Anne (author)
  • Bourhis, Jean Henri (author)
  • Milpied, Noel (author)
  • Cornelissen, Jan (author)
  • Chevallier, Patrice (author)
  • Maertens, Johan (author)
  • Jindra, Pavel (author)
  • Blaise, Didier (author)
  • Lenhoff, StigLund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)med-slf (author)
  • Ifrah, Norbert (author)
  • Baron, Frédéric (author)
  • Ciceri, Fabio (author)
  • Gorin, Claude (author)
  • Savani, Bipin (author)
  • Giebel, Sebastian (author)
  • Polge, Emmanuelle (author)
  • Esteve, Jordi (author)
  • Nagler, Arnon (author)
  • Mohty, Mohamad (author)
  • Avdelningen för hematologi och transfusionsmedicinInstitutionen för laboratoriemedicin (creator_code:org_t)

Related titles

  • In:Blood: American Society of Hematology126:17, s. 2062-20691528-00200006-4971

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