Clinical impact of FLT3 mutation load in acute promyelocytic leukemia with t(15;17)/PML-RARA.

Abstract

BACKGROUND:

Combined treatment with all-trans-retinoic acid and chemotherapy is extremely efficient in patients with acute promyelocytic leukemia with t(15;17)/PML-RARA, but up to 15% of patients relapse.

DESIGN AND METHODS:

To further clarify the prognostic impact of parameters such as FLT3 mutations, we comprehensively characterized the relation between genetic features and outcome in 147 patients (aged 19.7-86.3 years) with acute promyelocytic leukemia.

RESULTS:

Internal tandem duplications of the FLT3 gene (FLT3-ITD) were detected in 47/147 (32.0%) and tyrosine kinase domain mutations (FLT3-TKD) in 19/147 (12.9%) patients. FLT3-ITD or FLT3-TKD mutation status did not have a significant prognostic impact, whereas FLT3-ITD mutation load, as defined by a mutation/wild-type ratio of less than 0.5 was associated with trends to a better 2-year overall survival rate (86.7% versus 72.7%; P=0.075) and 2-year event-free survival rate (84.5% versus 62.1%, P=0.023) compared to the survival rates of patients with a ratio of 0.5 or more. Besides the t(15;17), an additional chromosomal abnormality was detected in 57 of 147 cases and did not show a significant impact on survival. White blood cell counts of 10×10(9)/L or less versus more than 10×10(9)/L were associated with a better 2-year overall survival rate (88.3% versus 69.4%, respectively; P=0.015), as was male sex (P=0.040). In multivariate analysis, only higher age had a significant adverse impact.

CONCLUSIONS:

Prospective trials should further investigate the clinical impact of the FLT3-ITD/wild-type mutation load aiming to evaluate whether this parameter might be included in risk stratification in patients with acute promyelocytic leukemia.

• Authors: Susanne Schnittger, Ulrike Bacher, Claudia Haferlach, Wolfgang Kern, Tamara Alpermann, Torsten Haferlach
• Journal: Haematologica (Haematologica) Vol. 96 Issue 12 Pg. 1799-807 (Dec 2011) ISSN: 1592-8721 [Electronic] Italy
• PMID: 21859732 (Publication Type: Clinical Trial, Comparative Study, Journal Article)

Chemical References

• Antineoplastic Agents
• Oncogene Proteins, Fusion
• promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein
• Tretinoin
• FLT3 protein, human
• fms-Like Tyrosine Kinase 3

Topics

• Adult
• Aged
• Antineoplastic Agents (administration & dosage)
• Chromosomes, Human, Pair 15 (genetics)
• Chromosomes, Human, Pair 17 (genetics)
• Disease-Free Survival
• Female
• Humans
• Leukemia, Promyelocytic, Acute (drug therapy, genetics, mortality)
• Male
• Middle Aged
• Oncogene Proteins, Fusion (genetics)
• Survival Rate
• Translocation, Genetic
• Tretinoin (administration & dosage)
• fms-Like Tyrosine Kinase 3 (genetics)