Expression of eukaryotic initiation factor 4E predicts clinical outcome in patients with mantle cell lymphoma treated with hyper-CVAD and rituximab, alternating with rituximab, high-dose methotrexate, and cytarabine

Inamdar, Kedar V. ; Romaguera, Jorge E. ; Drakos, Elias ; Knoblock, Ronald J. ; Garcia, Mar ; Leventaki, Vasiliki ; Medeiros, L. Jeffrey ; Rassidakis, George Z.

Resumen: BACKGROUND:Oncogenic AKT/mammalian target of rapamycin (mTOR) signaling has recently been shownto contribute to tumor survival and proliferation in mantle cell lymphoma (MCL) through its downstreameffector eukaryotic initiation factor 4E (eIF4E), which may control cyclin D1 protein levels. However, the clini-cal significance of eIF4E expression in MCL is unknown.METHODS:The authors investigated the prognosticsignificance of eIF4E expression in 70 MCL patients uniformly treated with hyper-CVAD and rituximab,alternating with the rituximab, high-dose methotrexate, and cytarabine regimen (R-hyper-CVAD). eIF4Eexpression was assessed using tissue biopsy specimens obtained before treatment, immunohistochemicalmethods, and a highly specific monoclonal antibody. Failure-free (FFS) and overall (OS) survival were usedas endpoints in univariate and multivariate survival analysis.RESULTS:High eIF4E expression was found in28 (40%) MCL tumors. After a median follow-up of 51 months for survivors, the 5-year FFS was 20.6% forpatients with high eIF4E expression, compared with 63.5% for patients with low or no eIF4E expression (P¼.01, log-rank). Similarly, the 5-year OS was 40.1% for patients with high eIF4E expression, compared with73.8% for patients with low or no eIF4E expression (P¼.018, log-rank). In multivariate analysis, eIF4E expres-sion was associated with poorer FFS and OS, along with age>60 years and highb2–microglobulin in the finalprognostic model.CONCLUSIONS:In summary, eIF4E, which seems to recapitulate most of the biologiceffects of mTOR signaling in MCL, is an independent predictor of clinical outcome in MCL patients uniformlytreated with the R-hyper-CVAD regimen

Idioma: Inglés

DOI: 10.1002/cncr.24506

Año: 2009

Publicado en: CANCER 115, 20 (2009), 4727-4736
ISSN: 0008-543X

Factor impacto JCR: 5.418 (2009)

Categ. JCR: ONCOLOGY rank: 21 / 164 = 0.128 (2009) - Q1 - T1

Tipo y forma: Article