Treatment Of Acute Non-Lymphocytic Leukemia With 5-Azacitidine

5-azacitidine (5AZA), a 5-methyltransferase inhibitor that demethylates and unsilences genes is a novel medication with epigenetic mechanism of action approved for therapy of myelodysplastic syndromes. There are few reports in the literature regarding use in acute non-lymphocytic leukemia (ANLL) some indicating efficacy and others lack of efficacy. Since January 3, 2010, we treated 6 patients in various stages of ANLL with 5AZA. Data is summarized in table.

We treated 2 patients ages 63 and 65 with primary induction failure to standard 3+7 anthracycline/AraC, both with complex cytogenetics. One patient achieved hematological improvement following 1 cycle and complete remission at 3 months following 2 cycles of therapy. He continues to receive monthly 5AZA, is alive and in complete hematological remission (bone marrow not repeated) at 8+ months. The second patient achieved a partial remission at 1 month following 5AZA that remained stable on monthly 5AZA for 8 months at which time ANLL progressed resulting in death. We used 5AZA as induction and maintenance for a 93 year old with ANLL with normal cytogenetics. He achieved a partial then stable improvement with monthly 5AZA. At 12 months, ANLL progressed resulting in death. We treated a 68 year old with NPM1 positive normal cytogenetics ANLL who achieved remission with standard 3+7 therapy but at 6 months post induction developed secondary myelodysplasia. He achieved a stable partial response with monthly 5AZA for 14 months at which time ANLL relapsed. He is alive at the time of preparation of this abstract. We used 5AZA as maintenance for an 86 year old with ANLL with normal cytogenetics who achieved a complete remission with standard 3+7 therapy. This individual continues to receive 5AZA (monthly then every 6 weeks) and remains in complete remission 32+ months following diagnosis of ANLL. We treated a 72 year old with borderline RAEB-2/ANLL with NPM1 positive normal cytogenetics with 5AZA as primary induction therapy. He achieved a hematological response following 4 monthly cycles of 5AZA with normalization of platelets and decreased need for RBC support. ANLL relapsed at 8 months at which time he was treated with standard chemotherapy and lived an additional 11 months. This data indicates that 5AZA is useful for individuals with ANLL even with high risk cytogenetics with potential efficacy as primary therapy, for individuals with disease primary refractory to standard chemotherapy, and for maintenance of ANLL remission. Formal studies to more clearly define the role of 5AZA in various stages of ANLL are warranted.