5-Azacitidine Plus Vorinostat As Maintenance Therapy of Second Remission in AML Instead of High Doses of Consolidation with Cytarabine

Abstract 4348

Patients with refractory AML after failure of reinduction of remission treatment (usually the clasical 7+3) have few options of effective reinduction regimen. Once a second remission is obtained, the standard strategies implies an allogenic BMT or consolidation treatment with high doses of cytarabine but the BMT requires a match or alternative donor and the chemotherapy implies myelotoxicities and some patients have high risk of severe complications versus recurrent relapse and death.

A 36 years old male with AML M4 intermediate risk since april 2010 was treated conventionally with 7+3 regimen (Cytarabine + Idarubicin), after that he received 4 cycles of high doses of Cytarabine as consolidation. On October 2010 he received an autologous BMT (ABMT) because he does not have an HLA compatible donor. After 12 months of complete remission post ABMT he relapsed on October 2011. He received as reinduction regimen 7+3 (Cytarabine + Doxorubicin) and he failed to obtain remission. He received a salvage treatment with high dose of Cytarabine 3 gr/m2 (6 doses) followed by high doses of Etoposide 60 mg/kg in continuous infusion. He achieved complete remission and then developed Aspergillus pneumonia during the myelosupressed period and a thoracoscopy was performed for treatment, he was discharged at the end of November 2011.

In the face of the impossibility of conventional consolidation therapy, and in the presence of poor general conditions, we started a treatment model based on epigenetic alternative therapy with the objective to maintain remission. In December 2011 he was started an ambulatory treatment based on subcutaneous administration with 5-azacitidine 75mg/m2/day during 7 days every 28 days for two cycles; during treatment he developed myelosuppression without the need of stimulating factors or transfusions. Posteriorly he continued with two new cycles of 5-azacitidine 50mg/m2/day during 10 days plus Vorinostat 200 mg every 24 hours during 14 days. Each month since the beginning of the epigenetic therapy, BMA was performed with flow cytometry and immunophenotype performed that showed a persistent remission until May 2012 when he relapsed.

Therefore epigenetic therapy maintained in remission a high risk patient, improved his general conditions, and posteriorly allowed him to be able to receive an haploidentical bone marrow transplant.