The Use of 5-Azacitidine in Allogeneic Hematopoietic Cell Transplantation: A Single Center Experience

INTRODUCTION: The allogeneic hematopoietic cell transplantation (alloHCT) remains the only treatment modality with known curative potential in MDS, AML and CMML. The 5-azacitidine is the first line treatment in high-risk MDS that are not suitable for intensive therapy. On the other hand, there is not enough evidence for deciding which is the best option, either 5-azacitidine or induction chemotherapy, before alloHCT. In a similar way, the 5-azacitidine exposure in post-alloHCT relapse may be an attractive alternative, even though there are not definite results yet.

OBJECTIVE: Evaluate the capacity of 5-azacitidine in reducing or stabilizing the disease before alloHCT, regarding associated toxicity, and its role in post-alloHCT relapses.

PATIENTS AND METHODS: We retrospectively reviewed 36 patients who underwent alloHCT for high-risk MDS, AML and CMML between October 2006 and September 2012 in our center and who received 5-azacitidine before and/or after alloHCT.

RESULTS: 30 patients received 5-azacitidine pre-alloHCT, 22 were MDS (73%), 6 AML (22%) and 2 CMML (7%), with high-risk cytogenetic (according to IPSS-R) in one third of them. The median of cycles was 5 (1-12), using the conventional dose and schedule, and presenting usual toxicity in only 38% of cases. Two thirds of evaluable patients achieved complete remission (CR) or partial response (PR) and 26% progressed. 83% of patients underwent alloHCT in some type of response and 17% in progression. The alloHCT characteristics were: median of age of 56 (35-67), peripheral blood as source of stem cells in 93%, related donor in 62%, and reduced-intensity conditioning in most cases (83%). At day +100, 82% of patients achieved CR and 18% had progressed. The global post-alloHCT relapse rate was 33%. The 2-years overall survival (OS) and event-free survival (EFS) were 66% and 50%, respectively. At 1 year, the relapse-free survival (RFS) was 65%, without having reached the median follow-up. We did not observe any significant statistical differences in OS after taking into account the following factors: sex, diagnosis, previous lines of treatment, response to 5-azacitidine, response at alloHCT and type of donor. However, cytogenetic risk did significantly influence survival in terms of OS, EFS and RFS, the same as source of stem cells, type of conditioning regimen and response at day +100 in OS. 16 patients received 5-azacitidine after post-alloHCT relapse with a median of cycle of 3.5 (1-19), reduced dose in some cases and limited toxicity (42%). The median of days after alloHCT to the beginning of treatment was 152 (32-529). Two thirds of patients achieved CR and the 1-year OS in this group was 43%.

CONCLUSION: The 5-azacitidine is a treatment modality that can improve or stabilize the disease, allowing time for patients to reach alloHCT, with little toxicity, and can induce response after post-alloHCT relapses.