Effects Of Metformin Addition To a Standard Chemotherapy Regimen For The Treatment Of Adult Acute Lymphoblastic Leukemia. An In Vitro and In Vivostudy

Abstract

Antitumor effects of metformin are widely known. Unfortunately their use in the treatment of acute lymphoblastic leukemia is limited. Study designThe study consisted of two stagesPhase 1: Cell assay adding metformin (40mM) assessing the viability and cell cycle in the cell line molt 4Phase 2: Pilot study adding Metformin (850mg three time day) during the pre-treatment with steroids and the induction remission phase versus a control group (2:1 randomization) Statistical analysisChi-square analysis was used to corroborate the hypothesis. The odds ratio was calculated for both, the absence of Good steroid response and refractory leukemia. Cox regression analysis and Kaplan-Meier curves were used for the survival analysis ResultsCelular assay. Metformin inhibited cell viability at 120hours reducing the percentage of cells in phase S.Clinical assay. 151 patients were studied, 44 (29.1%) on Metformin arm, of these 59.1% ( n=26) archived a GSR compared with the control group (26.2%, n=28). A greater number of complete remission were presented in Metformin arm (81.8% versus 57.9%) shown to be a protective factor for GSR and complete remissions (odds ratio ; 0.2454 y 0.3062 respectively). In the Cox regression analysis, Metformin significantly impact in the global survival (p=0,012,95% IC) versus the other variables studied. ConclusionsMetformin is useful both in vivo and in vitro treatment of adult acute lymphoblastic leukemia. Disclosures:No relevant conflicts of interest to declare.