Experience Of A 5-Day Schedule Of Azacitidine In A Single-Centre Acute Myeloid Leukemia Population

Abstract

Background. Acute Myeloid Leukemia(AML) is the most common type of acute Leukemia occurring in adults. First line Intensive chemotherapy would be the best treatment option but for some population, as elderly patients, who have poor performance status and other recognized poor prognostic factors may not be the most suitable option. Similarly, AML refractory or patients with an early relapse after induction, have a poor prognosis and limited therapeutics options. For both cases, preliminary studies with 5-Azacitidine seems to be an active and well tolerated drug pending to be corroborated in further prospective studies. Aims. To describe our experience with 5-Azacitidine in unfit or no candidate for intensive chemotherapy and relapse/resistant AML patients and to compare it with previous data reports in the literature. Methods. We include in these study all AML patients (and 4 high-risk MDS) treated in our center with 5-Aza. The protocol used was 75 mg/m2/day intravenous for 5 consecutive days every 28 days. Data of responses were described according to IWG criteria. Results. 20 patients were included, 16male/4Female, with a median age of 73. 5 years (39-81) with 16 patients(80%) >65 years. According to WHO criteria, 16 were AML (4 unfit untreated, 12 relapse/resistance) and 4 MDS (all four with high risk IPSS and severe transfusion dependence, 3 unfit-untreated, 1 relapse/resistance). 3/20 patients are separately reported because they began 5-Aza as a consolidation/maintenance in Complete Remission(CR) after a cycle of chemotherapy induction. Median pre-treatment Bone Marrow blasts percentage in AML patients was 31%(6-90). Karyotype was evaluable in all patients, 11(74. 8%) adverse-risk, 6(35. 2%) intermediate-risk). A total of 83 treatment cycles were administered with a median of 3 cycles (1-18) (all patients included, at least completed 1 cycle). After a median follow up of 8. 3 month (1-21), 7/17(41. 1%) had some kind of response (CR/partial remission/hematology improvement(HI) and Stable disease(SD). With 3 CR(17. 64%) and 4 SD(23. 5%) We did not find any PR or HI. The median response duration of CR was 5 month (3-9). The median overall survival(OS) time of the whole cohort was 4. 9 month (0. 4-23,3). OS in the adverse and intermediate-risk Karyotype group was 4. 35 and 6,6 month respectively and in the unfit-untreated and relapse/resistance patients was 5. 03 and 4. 9 month. In the 3 patients who began 5-Aza in CR after induction therapy the median OS and EFS was 25. 3 and 10. 8 month respectively. Conclusions. As this is a retrospective study with a small simple size and heterogenety among the patients, it is not posible to stablish statistically significant results. Taking this facts into account, we can conclude that our OS, CR, DFS data and the difference by cytogenetic risk group, coincide with what have been published in the literature. In the same way, OS and DFS data obtained in our 3 patients on maintenance treatment are also similar to what have been described in similar AML patients after induction treatment. Therefore, these preliminary data encourage us to continue in this line of treatment, as well as to widen and improve our study in this poor prognosis patients with limited treatment options.