Hypomethylating Therapy for the Treatment of Acute Erythroleukemia Patients.

Erythroleukemia characteristically presents with profound cytopenias with multilineage dysplasia that is often accompanied by unfavorable cytogenetics. Results of standard cytarabine–based induction regimens are with a reported median survival of 11 months. Hypomethylating agents have demonstrated clinical activity in patients with myelodysplastic syndromes (MDS), improving survival nearly 3-fold in patients with poor risk cytogenetics in the AZA-001 trial. Aim: To determine the clinical efficacy of hypomethylating agents among patients with erythroleukemia. Methods: Records were reviewed from all patients with erythroleukemia treated with hypomethylating agents in two institutions (MD Anderson Cancer Center and Moffitt Cancer Center). Between November 2002 and July 2007, 17 patients with the diagnosis of acute erythroleukemia received hypomethylating agents as part of their therapy. Results: The median age was 68 years (range,38-79), 4 (24%) were females. Treatment was with azacytidine (AZA) in 11 (65%) and with decitabine (DAC) in 6 (35%) of the cases. In 5 patients, hypomethylating agents (1 AZA, 4 DAC) were combined with histone deacetylase inhibitors (valproic acid) including ATRA in 1 case. 14 patients received therapy with hypomethylating agents as induction therapy, 2 received tipifarnib, one received midostaurine, with hypomethylating agents reserved for salvage therapy. Cytogenetic analysis included diploid in 4, complex abnormalities in 9, and intermediate risk in 4. FLT3 mutations were absent in all 9 patients tested. 14 patients had a preceding history of MDS. Ten (58%) of the 17 patients achieved a complete remission (CR); this was accompanied by complete cytogenetic remission in 10 of 13 evaluable patients. The median number of cycles to achieve CR was 3 (range, 2 to 4) and for cytogenetic response 3. After a median follow up of 48 weeks, 7 patients relapsed, with a median duration of remission of 17 weeks. Patients received a median of 5 cycles (2 to 12). Treatment was overall well tolerated. The most common non-hematologic toxicities included fatigue. Grade 3-4 toxicity included severe thrombocytopenia and sepsis in one case respectively, with no treatment related deaths. 4 patients proceeded to an allogeneic stem cell transplant while in remission. The median disease-free survival was 11 months with 24% projected alive and free of disease by 24 months. The median survival is 12 months with 30% projected to be alive at 24 months. Conclusions: These results suggest that hypomethylating agents are highly active in patients with acute Erythroleukemia and may extend survival compared to standard induction. These results should be confirmed in prospective clinical trials, and combination therapy based on hypomethylating therapy could also be explored.

Off Label Use: Decitabine and Azacitidine are not approved for treatment in acute erythroleukemia.. Lancet:Celgene: Research Funding.