When is the optimal timing for allogeneic transplantation in the case of MDS patients treated with hypomethylating agents?

Although the use of hypomethylating agents (HMAs) has improved the response rates and survival rates in myelodysplastic syndrome (MDS) patients, the cure rate is negligible, even for responders to HMA, suggesting the necessity for allogeneic transplantation at some point during HMA therapy prior to overt relapse or progression to acute myelogenous leukemia. However, in practice, deciding on the optimal timing for transplantation is difficult in the case of low/intermediate-1-risk MDS patients under hematologic complete remission with HMA. There is also a remaining question on the role of debulking treatment with the frontline use of HMA in intermediate-2/high-risk MDS patients who are eligible for transplantation. Therefore, our recommendations on the optimal timing of allogeneic transplantation are as follows: for low/intermediate-1-risk MDS patients, start HMA and continue it in responders, then transplantation needs to be performed at the time of a decreasing platelet count before overt relapse or progression to acute myelogenous leukemia. For intermediate-2/high-risk MDS patients, HMA may be indicated as a frontline treatment in all cases, regardless of transplant eligibility, considering its positive role of debulking and lack of negative impact on transplant outcomes. However, HMA therapy has not been approved for the patients eligible for allogeneic transplantation at present. Our suggestions need to be evaluated through a large study in the future.