Prognostic impact of DNMT3A mutation in acute myeloid leukemia with mutated NPM1.
Por:
Onate G, Bataller A, Garrido A, Hoyos M, Arnan M, Vives S, Coll R, Tormo M, Sampol M, Escoda L, Salamero O, Garcia A, Bargay J, Aljarilla A, Nomdedeu J, Esteve J, Sierra J, Pratcorona M
Publicada:
8 feb 2022
Ahead of Print:
1 feb 2022
Resumen:
The negative prognostic impact of internal tandem duplication of FLT3 (FLT3-ITD) in patients with acute myeloid leukemia with mutated NPM1 (AML-NPM1) is restricted to those with a higher FLT3-ITD allelic ratio (FLT3high; =0.5) and considered negligible in those with a wild-type (FLT3WT)/low ITD ratio (FLT3low). Because the comutation of DNMT3A (DNMT3Amut) has been suggested to negatively influence prognosis in AML-NPM1, we analyzed the impact of DNMT3Amut in FLT3-ITD subsets (absent, low, and high ratios). A total of 164 patients diagnosed with AML-NPM1 included in 2 consecutive CETLAM protocols and with DNMT3A and FLT3 status available were studied. Overall, DNMT3Amut status did not have a prognostic impact, with comparable overall survival (P = .2). Prognostic stratification established by FLT3-ITD (FLT3WT = FLT3low > FLT3high) was independent of DNMT3Amut status. Measurable residual disease (MRD) based on NPM1 quantitative polymerase chain reaction was available for 94 patients. DNMT3Amut was associated with a higher number of mutated NPM1 transcripts after induction (P = .012) and first consolidation (C1; P < .001). All DNMT3Amut patients were MRD+ after C1 (P < .001) and exhibited significant MRD persistence after C2 and C3 (MRD+ vs MRD-; P = .027 and P = .001, respectively). Finally, DNMT3Amut patients exhibited a trend toward greater risk of molecular relapse (P = .054). In conclusion, DNMT3Amut did not modify the overall prognosis exerted by FLT3-ITD in AML-NPM1 despite delayed MRD clearance, possibly because of MRD-driven preemptive intervention.
Filiaciones:
Onate G:
Autonomous University of Barcelona, Spain
Bataller A:
Hospital Clínic de Barcelona, Barcelona, Spain
Garrido A:
Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Hoyos M:
Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Arnan M:
Catalan Institute of Oncology
Vives S:
ICO-Hospital Germans Trias i Pujol, Badalona, Spain
Coll R:
Haematological Services, ICO GIRONA, Girona, Spain
Tormo M:
Hospital Clinico Universitary. INCLIVA Research Institute, Valencia 46010, Spain
Sampol M:
Hospital Universitario Son Espases, Palma de Mallorca, Spain
Escoda L:
ICO-Hosp Joan XXIII, Tarragona, Spain
Salamero O:
Hospital Universitari de la Vall d' Hebron, VHIO, Barcelona, Spain
Garcia A:
Hospital Arnau de Vilanova
Bargay J:
hospital Son LLatzer .Instituto Investigación Sanitaria Illes Balears( IdISBa), Palma Mallorca, Spain
Aljarilla A:
Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Nomdedeu J:
Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Esteve J:
IDIBAPS, Hospital Clinic
Sierra J:
Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Pratcorona M:
Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Green Published, gold, Green Submitted
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