Abstract
Hypomethylating agents, decitabine (DAC) and azacitidine, can act as prophylactic and pre-emptive approaches after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and a non-intensive bridging approach before allo-HSCT. However, they are rarely used as a part of conditioning regimens in patients with relapsed or refractory acute myeloid leukemia (AML). This retrospectively study included a total of 65 patients (median, 37; range, 13–63) with relapsed or refractory AML who were treated by allo-HSCT after myeloablative conditioning regimens without or with DAC (high-dose DAC schedule, 75 mg/m2 on day −9 and 50 mg/m2 on day −8; low-dose DAC schedule, 25 mg/m2/day on day −10 to −8). DAC exerted no impact on hematopoietic reconstitution. However, patients who were treated with the high-dose DAC schedule had significantly higher incidence of overall survival (OS, 50.0%) and leukemia-free survival (LFS, 35.0%), and lower incidence of relapse (41.1%) and grade II–IV acute graft versus host disease (aGVHD, 10.0%) at 3 years, when compared with those treated with standard conditioning regimens or with the low-dose DAC schedule. In conclusion, high-dose DAC combined with standard conditioning regimens before allo-HSCT is feasible and efficient and might improve outcomes of patients with relapsed or refractory AML, which provides a potential approach to treat these patients.
Highlights
With significant advances in the treatment of acute myeloid leukemia (AML), 60%–80% of AML patients can achieve complete remission (CR) after standard induction chemotherapy consisting of anthracyclines and cytarabine [1]
There were no significant differences in variables of age, gender, AML type, AML classification, BM blast percentage, time from diagnosis of relapsed or refractory AML to transplant, donor human leukocyte antigens (HLA) type, gender relationship, ABO blood type, conditioning regimen, cytogenetics, disease status at transplantation, and infused cells between any two groups (p > 0.05)
Allo-HSCT provides a potentially curative option for AML, relapse remains as a main cause of treatment failure [19]
Summary
With significant advances in the treatment of acute myeloid leukemia (AML), 60%–80% of AML patients can achieve complete remission (CR) after standard induction chemotherapy consisting of anthracyclines and cytarabine [1]. Only 20%–30% of the patients with CR can achieve long-term leukemia-free survival [2], and over 50% of patients with CR will suffer from disease relapse, even death within 1 year [3]. For these patients, allogeneic hematopoietic stem cell transplantation (alloHSCT) provides the only curative option, by using an appropriate conditioning regimen that is critical to influence the success of alloHSCT [4]. DAC can alleviate the graft versus host disease (GVHD) by modulating regulatory T cells [10] These advantages of DAC make it an attractive drug in conditioning regimens before allo-HSCT
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