Prognostic value of FLT3 mutations in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy
Barragán, Eva; Montesinos, Pau; Camos, Mireia; González, Marcos; Calasanz, María J; Román-Gómez, José; Gómez-Casares, María T.; Ayala, Rosa; López, Javier; Fuster, Óscar; Colomer, Dolors; Chillón, Carmen; Larrayoz, María J.; Sánchez-Godoy, Pedro; González-Campos, José; Manso, Félix; Amador Barciela, María Lourdes; Vellenga, Edo; Lowenberg, Bob; Sanz, Miguel A
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Identificadores
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Autor corporativo
PETHEMA Group; HOYON GroupFecha de publicación
2011Título de revista
Haematologica
Tipo de contenido
Artigo
Resumen
Background
Fms-like tyrosine kinase-3 (FLT3) gene mutations are frequent in acute promyelocytic leukemia
but their prognostic value is not well established.
Design and Methods
We evaluated FLT3-internal tandem duplication and FLT3-D835 mutations in patients treated
with all-trans retinoic acid and anthracycline-based chemotherapy enrolled in two subsequent
trials of the Programa de Estudio y Tratamiento de las Hemopatías Malignas (PETHEMA) and
Hemato-Oncologie voor Volwassenen Nederland (HOVON) groups between 1996 and 2005.
Results
FLT3-internal tandem duplication and FLT3-D835 mutation status was available for 306 (41%)
and 213 (29%) patients, respectively. Sixty-eight (22%) and 20 (9%) patients had internal tandem duplication and D835 mutations, respectively. Internal tandem duplication was correlated
with higher white blood cell and blast counts, lactate dehydrogenase, relapse-risk score, fever,
hemorrhage, coagulopathy, BCR3 isoform, M3 variant subtype, and expression of CD2, CD34,
human leukocyte antigen-DR, and CD11b surface antigens. The FLT3-D835 mutation was not
significantly associated with any clinical or biological characteristic. Univariate analysis
showed higher relapse and lower survival rates in patients with a FLT3-internal tandem duplication, while no impact was observed in relation to FLT3-D835. The prognostic value of the
FLT3-internal tandem duplication was not retained in the multivariate analysis.
Conclusions
FLT3-internal tandem duplication mutations are associated with several hematologic features
in acute promyelocytic leukemia, in particular with high white blood cell counts, but we were
unable to demonstrate an independent prognostic value in patients with acute promyelocytic
leukemia treated with all-trans retinoic acid and anthracycline-based regimens.
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