Resum
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 (FLT3 high ; ≥0.5) and considered negligible in those with a wild-type (FLT3 WT)/low ITD ratio (FLT3 low). Because the comutation of DNMT3A (DNMT3A mut) has been suggested to negatively influence prognosis in AML- NPM1, we analyzed the impact of DNMT3A mut 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, DNMT3A mut status did not have a prognostic impact, with comparable overall survival (P =.2). Prognostic stratification established by FLT3 -ITD (FLT3 WT = FLT3 low > FLT3 high) was independent of DNMT3A mut status. Measurable residual disease (MRD) based on NPM1 quantitative polymerase chain reaction was available for 94 patients. DNMT3A mut was associated with a higher number of mutated NPM1 transcripts after induction (P =.012) and first consolidation (C1; P <.001). All DNMT3A mut 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, DNMT3A mut patients exhibited a trend toward greater risk of molecular relapse (P =.054). In conclusion, DNMT3A mut did not modify the overall prognosis exerted by FLT3 -ITD in AML- NPM1 despite delayed MRD clearance, possibly because of MRD-driven preemptive intervention.
| Idioma original | English |
|---|---|
| Pàgines (de-a) | 0882-890 |
| Nombre de pàgines | 9 |
| Revista | Blood advances |
| Volum | 6 |
| DOIs | |
| Estat de la publicació | Publicada - 2022 |
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Oñate, G., Bataller, A., Garrido, A., Hoyos Colell, M., Arnan, M., Vives Polo, S., Coll, R., Tormo, M., Sampol, A., Escoda, L., Salamero, O., Garcia, A., Bargay, J., Aljarilla, A., Nomdedeu, J., Esteve Reyner, J., Sierra, J., & Pratcorona, M. (2022). Prognostic impact of DNMT3A mutation in acute myeloid leukemia with mutated NPM1. Blood advances, 6, 0882-890. https://doi.org/10.1182/bloodadvances.2020004136
Oñate, Guadalupe ; Bataller, Alex ; Garrido, Ana et al. / Prognostic impact of DNMT3A mutation in acute myeloid leukemia with mutated NPM1. In: Blood advances. 2022 ; Vol. 6. pàg. 0882-890.
@article{f6da50a0cf3b47cf85f5602fa8df92e2,
title = "Prognostic impact of DNMT3A mutation in acute myeloid leukemia with mutated NPM1",
abstract = "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 (FLT3 high ; ≥0.5) and considered negligible in those with a wild-type (FLT3 WT)/low ITD ratio (FLT3 low). Because the comutation of DNMT3A (DNMT3A mut) has been suggested to negatively influence prognosis in AML- NPM1, we analyzed the impact of DNMT3A mut 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, DNMT3A mut status did not have a prognostic impact, with comparable overall survival (P =.2). Prognostic stratification established by FLT3 -ITD (FLT3 WT = FLT3 low > FLT3 high) was independent of DNMT3A mut status. Measurable residual disease (MRD) based on NPM1 quantitative polymerase chain reaction was available for 94 patients. DNMT3A mut was associated with a higher number of mutated NPM1 transcripts after induction (P =.012) and first consolidation (C1; P <.001). All DNMT3A mut 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, DNMT3A mut patients exhibited a trend toward greater risk of molecular relapse (P =.054). In conclusion, DNMT3A mut did not modify the overall prognosis exerted by FLT3 -ITD in AML- NPM1 despite delayed MRD clearance, possibly because of MRD-driven preemptive intervention.",
author = "Guadalupe O{\~n}ate and Alex Bataller and Ana Garrido and {Hoyos Colell}, Montserrat and Montserrat Arnan and {Vives Polo}, Susana and Rosa Coll and Mar Tormo and Antonia Sampol and Lourdes Escoda and Olga Salamero and Antoni Garcia and Joan Bargay and Alba Aljarilla and Josep Nomdedeu and {Esteve Reyner}, Jordi and Jorge Sierra and Marta Pratcorona",
year = "2022",
doi = "10.1182/bloodadvances.2020004136",
language = "English",
volume = "6",
pages = "0882--890",
}
Oñate, G, Bataller, A, Garrido, A, Hoyos Colell, M, Arnan, M, Vives Polo, S, Coll, R, Tormo, M, Sampol, A, Escoda, L, Salamero, O, Garcia, A, Bargay, J, Aljarilla, A, Nomdedeu, J, Esteve Reyner, J, Sierra, J & Pratcorona, M 2022, 'Prognostic impact of DNMT3A mutation in acute myeloid leukemia with mutated NPM1', Blood advances, vol. 6, pàg. 0882-890. https://doi.org/10.1182/bloodadvances.2020004136
Prognostic impact of DNMT3A mutation in acute myeloid leukemia with mutated NPM1. / Oñate, Guadalupe; Bataller, Alex; Garrido, Ana et al.
In: Blood advances, Vol. 6, 2022, pàg. 0882-890.
Producció científica: Contribució a una revista › Article › Recerca › Avaluat per experts
TY - JOUR
T1 - Prognostic impact of DNMT3A mutation in acute myeloid leukemia with mutated NPM1
AU - Oñate, Guadalupe
AU - Bataller, Alex
AU - Garrido, Ana
AU - Hoyos Colell, Montserrat
AU - Arnan, Montserrat
AU - Vives Polo, Susana
AU - Coll, Rosa
AU - Tormo, Mar
AU - Sampol, Antonia
AU - Escoda, Lourdes
AU - Salamero, Olga
AU - Garcia, Antoni
AU - Bargay, Joan
AU - Aljarilla, Alba
AU - Nomdedeu, Josep
AU - Esteve Reyner, Jordi
AU - Sierra, Jorge
AU - Pratcorona, Marta
PY - 2022
Y1 - 2022
N2 - 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 (FLT3 high ; ≥0.5) and considered negligible in those with a wild-type (FLT3 WT)/low ITD ratio (FLT3 low). Because the comutation of DNMT3A (DNMT3A mut) has been suggested to negatively influence prognosis in AML- NPM1, we analyzed the impact of DNMT3A mut 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, DNMT3A mut status did not have a prognostic impact, with comparable overall survival (P =.2). Prognostic stratification established by FLT3 -ITD (FLT3 WT = FLT3 low > FLT3 high) was independent of DNMT3A mut status. Measurable residual disease (MRD) based on NPM1 quantitative polymerase chain reaction was available for 94 patients. DNMT3A mut was associated with a higher number of mutated NPM1 transcripts after induction (P =.012) and first consolidation (C1; P <.001). All DNMT3A mut 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, DNMT3A mut patients exhibited a trend toward greater risk of molecular relapse (P =.054). In conclusion, DNMT3A mut did not modify the overall prognosis exerted by FLT3 -ITD in AML- NPM1 despite delayed MRD clearance, possibly because of MRD-driven preemptive intervention.
AB - 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 (FLT3 high ; ≥0.5) and considered negligible in those with a wild-type (FLT3 WT)/low ITD ratio (FLT3 low). Because the comutation of DNMT3A (DNMT3A mut) has been suggested to negatively influence prognosis in AML- NPM1, we analyzed the impact of DNMT3A mut 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, DNMT3A mut status did not have a prognostic impact, with comparable overall survival (P =.2). Prognostic stratification established by FLT3 -ITD (FLT3 WT = FLT3 low > FLT3 high) was independent of DNMT3A mut status. Measurable residual disease (MRD) based on NPM1 quantitative polymerase chain reaction was available for 94 patients. DNMT3A mut was associated with a higher number of mutated NPM1 transcripts after induction (P =.012) and first consolidation (C1; P <.001). All DNMT3A mut 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, DNMT3A mut patients exhibited a trend toward greater risk of molecular relapse (P =.054). In conclusion, DNMT3A mut did not modify the overall prognosis exerted by FLT3 -ITD in AML- NPM1 despite delayed MRD clearance, possibly because of MRD-driven preemptive intervention.
U2 - 10.1182/bloodadvances.2020004136
DO - 10.1182/bloodadvances.2020004136
M3 - Article
C2 - 34516636
SN - 2473-9537
VL - 6
SP - 882
EP - 890
JO - Blood advances
JF - Blood advances
ER -
Oñate G, Bataller A, Garrido A, Hoyos Colell M, Arnan M, Vives Polo S et al. Prognostic impact of DNMT3A mutation in acute myeloid leukemia with mutated NPM1. Blood advances. 2022;6:0882-890. doi: 10.1182/bloodadvances.2020004136
