ts may induce hematological responses and increase life expectancy in elderly patients. However, management of patients MedChemExpress Ki-8751 following epigenetic therapy failure is not consensual and best supportive care is still proposed for most of these patients. Thus, new therapeutic strategies are strongly needed in this population of AML patients unfit or relapsing/refractory to high dose chemotherapy. Following the success of differentiating therapies in acute promyelocytic leukemia, great hopes were placed in Vitamin D and its ability to promote monocyte differentiation of non-APL AML cells. However, results of clinical studies were disappointing and trials were interrupted due to the occurrence of life-threatening hypercalcemia. Most elderly patients diagnosed with AML exhibit secondary iron overload because of iterative red blood cell transfusions and, in some cases, an increased of iron absorption due to ineffective erythropoiesis. Interestingly, in myelodysplastic syndromes, retrospective studies have suggested that iron chelators may increase life expectancy and may decrease the risk of transformation into AML although the molecular mechanism involved remains unknown. It has been shown that deferasirox, DFX is able to induce AML cells apoptosis in vitro through inhibition of NF-kB pathway. In addition, our group has shown that in 22441874 vitro iron chelators are able to promote monocyte differentiation in both normal hematopoietic progenitors and primary AML cells and that iron privation agents acted Deferasirox and Vitamin D on 
Leukemia synergistically with VD to promote cell differentiation. Because of cumulated evidences from experimental data and that both iron chelators and VD analogues are safe drugs and currently used in AML patients, we proposed deferasirox and 25-hydroxycholecalciferol combination therapy to a 69-yr-old AML patient, who was refractory to high dose chemotherapy. DFX/ VD treatment was associated with reduced blast counts and partial reversal of pancytopenia, accompanied by an increase in monocyte numbers derived from the blast pool. This casestudy suggested that the combined DFX/VD therapy could act as a differentiating agent in human AML. Taken together, these observations provided 17594192 a strong rationale for the use of iron chelators/VD therapy in the setting of high risk or relapsing AML elderly patients after failure or not fit enough for chemotherapy. Since VD deficiency and iron overload prevalence is high in the elderly AML patients, the association of VD and DFX was given to a subgroup of patients following demethylating agents failure. Here we report a case-control retrospective study aiming to investigate the therapeutic potential of the association of VD and DFX in elderly AML patients following demethylating agents failure. We show that patients who received this combination therapy presented an increased overall survival and that VD serum level was the stronger factor that positively correlated with overall survival. blood tests panels or AML prognostic factors between combination therapy and BSC. In each case, the dose of DFX was adapted based on ferritin and creatinine levels. DFX initial dose was of 2030 mg/kg per day and VD was used at 100,000 units orally weekly. Ethics Statement This study received ethics approval from the Human Ethics Committee of the Necker hospital. According to French legislation no written consents are necessary for observational retrospective studies. All data were analyzed anonymously. Each
