Durable complete remission after azacitidine treatment in a patient with Erythroleukaemia

To the Editor: In August 2010, a 79-yr-old man was diagnosed with AEL. The patient was well preserved and besides hypertension had no significant intercurrent diseases. The patient was admitted to hospital after a GI haemorrhage; endoscopy found no cause, but blood samples showed mild pancytopenia with haemoglobin of 11.3 g/dL, leucocytes of 1.5 9 10/L with neutrophils of 0.35 9 10/L and platelets of 36 9 10/L. A bone marrow biopsy and aspirate was performed. The bone marrow sample showed 22% myeloblast cells and >50% erythroid precursors. Thus, the AML was classified as FAB M6 and, according to the 2008 WHO classification, as erythroleukaemia, which is the most common subtype of AEL. Azacitidine treatment was started with 100 mg/m subcutaneously on days 1–5 every 4 wk (to avoid treatment during weekends). Prophylactic antibiotics were administered during the first three courses, where neutrophils were below 0.5 9 10/L. Besides injection-related erythema and slight pain, the patient had no side effects. Currently, the patient has been treated for 18 months and received a total of 18 azacitidine treatment series, the last 16 courses at a 20% dose reduction, owing to slight myelosupression following the first two courses. Following treatment the peripheral blood counts increased as shown in the figure. In December 2010, after five courses of therapy, a bone marrow sampling was performed, showing no erythroblasts and a reduction in myeloblasts to 15% compatible with RAEB-2. In October 2011, following course 12, a bone marrow sample showed further improvement, that is, the BM demonstrated persisting multilineage dysplasia with a reduction of blasts to <5%, which is compatible with complete remission according to Cheson criteria (1). The patient has so far lived 18 months after diagnosis and is still in complete remission with a good quality of life, capable of travelling, with no hospital admissions, and the patient only received one unit of blood so far. To our knowledge, this is the first report describing activity of azacitidine in AEL, which generally is considered to have a poor prognosis. Our finding needs confirmation in a larger cohort of AEL patients preferentially treated in a prospective multicenter trial of patients, who are not candidates for intensive chemotherapy and/or allogeneic stem cell transplantation. Epigenetic treatment with 5-azacitidine, a DNA methyltransferase inhibitor, is approved as first-line treatment for patients with advanced MDS and MDS/AML with <30% blasts, who are not candidates for allogeneic stem cell transplantation. First-line treatment with azacitidine was established after Fenaux et al. published the results of a large multicenter study in 2009. In the study, 358 patients with IPSS Int-2 and high-risk MDS, MDS/AML with <30% blasts (previous RAEB-t) and advanced, non-proliferative CMML-2 were included. The patients were randomized to receive either azacitidine or conventional care (best supportive care alone, best supportive care and low-dose cytarabine or intensive chemotherapy), which was selected before randomization. Azacitidine was given subcutaneously as 75 mg/ m/d for 7 d every 28 d. The results for the primary outcome, overall survival, showed a significant longer median overall survival in the azacitidine group of 24.5 months, compared with 15 months in the conventional care group (P = 0.0001) (2). There are only a few publications describing azacitidine treatment in patients with AML (either de novo or following MDS) with more than 30% blasts and specifically no reports regarding azacitidine in patients with erythroleukaemia (3, 4). Acute erythroid leukaemia (AEL) represents <5% of all cases of AML. AEL are acute leukaemias that are characterized by a predominant erythroid population. There are two subtypes: