Introduction Acute erythroleukemia AEL is a
Acute erythroleukemia (AEL) is a rare subtype of acute myeloid leukemia (AML), accounting for 3–5% of all AML cases. It is characterized by the expansion of erythroblasts in the bone marrow (BM). Its clinical presentation often resembles myelodysplastic syndromes (MDS), both in terms of indolent cytopenias and older median age at diagnosis of 65. High risk karyotypes, with hypodiploidy, complex alterations (including abnormalities of GSK-J1 sodium salt 5 and 7) and monosomies are frequent. Consequently, AEL is associated with poor prognosis, with a median survival of 3–9 months from diagnosis.
It is traditionally treated with intensive chemotherapy, achieving rates of complete remission (CR) of approximately 55% but these last less than a year. As in other AML subtypes, patients with high risk cytogenetics should be considered for allogeneic bone marrow transplant. However, the fact that most patients are elderly and frail means that aggressive treatment options are often not possible, limiting management to supportive care.
In the last few years hypomethylating agents have become the first line therapy for patients with MDS and AML who are not candidates for aggressive chemotherapy, including bone marrow transplantation. Azacitidine has demonstrated to grant patients with high risk MDS and AML with 20–30% blasts a survival advantage compared to conventional care regimens.
There are several reports of use of Azacitidine in AEL, including a series of 17 patients, where CR was achieved in 58%, median disease free survival of 11 months and median survival of 12 months.
Although the standard AZA administration schedule is 75mg/m2/day for 7 days every 28 days (75×7), at our institution, due to lack of availability of weekend administration and patient travel constraints, we adopted an alternate dose-intensified schedule over a shorter period of time (500mg/m2 total monthly dose divided in 5 days) with daily dose adjustment in order to avoid weekend administration and vial wastage. Using this regimen in high risk MDS patients we have observed similar efficacy and safety profiles as those published with the 75×7 schedule.
Discussion AEL is a rare subtype of AML commonly associated with previous myelodysplasia, complex karyotype and poor prognosis. Conventional treatment options are often limited, raising the need for novel approaches. Azacitidine, licensed for use in high risk MDS, has demonstrated efficacy in a small series of AEL patients. Our report differs from the only other published report of hypomethylating agents in erythroleukemia in several aspects. Our patient group is more uniform: all patients were treated with AZA as monotherapy compared to 35% who were treated with decitabine and 30% who received concomitant histone deacetylase inhibitors. The proportion receiving AZA as second line therapy was similar to Linker DNA previously published. The response rate was similar but treatment duration and overall survival in our cohort were longer: 10 cycles compared to 5 cycles and median survival of 22 months compared to 12 months. In patient 1, who had been refractory to intensive chemotherapy, Azacitidine permitted disease control for over 1 year during the search for a compatible bone marrow donor and preparation for SCT. Reduced intensity conditioning regimens have opened the option of SCT to more elderly and frail patients but the toxicities associated with conventional intensive AML induction chemotherapy can increase the risk of death or compromise SCT. It has been shown recently that Azacitidine before SCT does not significantly affect rates of remission, relapse, acute and chronic GVHD and survival after transplant and may actually be an alternative for inducing remission in patients with high risk MDS and eventually AEL.
Introduction Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell disorders associated with worsening cytopenias and leading to reduced survival and a compromised quality of life. Treatment for MDS patients with low-risk disease generally requires the management of the patient\'s symptomatic anemia with its attendant fatigue. Patients with severe thrombocytopenia (rarely the only cytopenia) also require supportive management. The prevalence of thrombocytopenia <100×109/l in MDS ranges from 33% to 76%. Severe thrombocytopenia is generally managed with platelet (PLT) transfusion support (at levels ≤10×109 or ≤20×109/l for clinical bleeding). Peri-operative platelet transfusion support is often needed for patients with even higher PLT counts due to their frequent thrombocytopathy.