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. 2011 Oct;96(10):1470-7.
doi: 10.3324/haematol.2011.044933. Epub 2011 Jun 17.

Prognostic value of FLT3 mutations in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy

Eva Barragán  1 , Pau Montesinos, Mireia Camos, Marcos González, Maria J Calasanz, José Román-Gómez, Maria T Gómez-Casares, Rosa Ayala, Javier López, Óscar Fuster, Dolors Colomer, Carmen Chillón, María J Larrayoz, Pedro Sánchez-Godoy, José González-Campos, Félix Manso, Maria L Amador, Edo Vellenga, Bob Lowenberg, Miguel A Sanz; PETHEMA; HOVON Groups
Collaborators, Affiliations

Prognostic value of FLT3 mutations in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy

Eva Barragán et al. Haematologica. 2011 Oct.

Abstract

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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Figures

Figure 1.
Figure 1.
Relapse-free survival in APL patients according to FLT3-ITD mutation status.
Figure 2.
Figure 2.
Relapse-free survival in FLT3-ITD positive APL patients according to ITD size.
See this image and copyright information in PMC

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