Efficacy and Safety of Decitabine Combined with FB3 As Conditional Regimen for Elderly/Frail Acute Myeloid Leukemia Patient with Allo-HSCT
Authors: Gao Shichun , Zhu Lidan , Liu Jia , Liu Huanfeng , Wang Lu , Kong Peiyan , Zhang Cheng , Gao Li , Chen Ting , Feng Yimei , Liu Yuqing , Yao Han , Zhao Lu , Gao Lei , Zhang Xi 
Published: December 2024

Objective Acute myeloid leukemia (AML) is one of the most common malignant hematological diseases, with a median age of 65 years. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important means for the treatment of AML. Elderly and frail AML patients are difficult to bear the myeloablative conditioning, and transplantation-related mortality (TRM) is significantly higher than that of young AML patients. How to reduce TRM in elderly / frail AML patients, improve the efficacy of allo-HSCT, and further expand the applicable population of allo-HSCT is a clinical problem worthy of discussion. Methods A retrospective analysis of patients who underwent allo-HSCT in our center from June 2016 to April 2022 and were older than 50 years old or HCT-CI score ≥ 3 points was performed using decitabine combined with FB3 regimen .Our center designed decitabine combined with FB3 (Dec+FB3) as conditional regimen (decitabine 20mg/m2 × 5days, fludarabine 30mg/m2 × 5days, busulfan 130mg/m2 × 3days) for elderly/frail AML patients with allo-HSCT. The historical control group was AML patients with age older than 50 years old and HCT-CI score ≤2 points who used BU+CTX (busulfan 0.8mg/kg q6h x 4days, cyclophosphamide 60mg/kg x 2days for HLA-identical hematopoietic stem cell transplantation and semustine (0.2g/m2 x 1day) + busulfan (0.8mg/kg q6h x 3days) + cyclophosphamide (1.8g/m2 x 2days) + cytarabine (2g/m2 q12h x 2days) +rabbit anti-human thymocyte immunoglobulin (2.5mg/kg x 4days) for HLA haploidentical HSCT (haplo-HSCT). The leukemia-free survival (LFS) rate, overall survival (OS) rate and incidence of transplantation-related complications were observed in two groups. Results Up to April 30, 2024, a total of 49 AML patients were enrolled in Dec+FB3 group, and 61 AML patients in the same period were included in the study as control. There was no significant difference between the two groups at other baseline levels except that the patients in Dec+FB3 group were significantly older than those in the control group (Table 1). All patients in the Dec+FB3 group had hematopoietic reconstitution, while one patient in the control group had no hematopoietic reconstitution. In Dec+FB3 group, the median time of neutrophil reconstruction was 15 (10-69) days, and the median time of platelet reconstruction was 16 (10-167) days. 10 patients died ( 5 patients died of infection,1 patient died of hepatic failure, 1 patient died of liver cancer for second tumor, and 3 patients died of relapse). In control group: the median time of neutrophil reconstruction was 15 (9-38) days, and the median time of platelet reconstruction was 16 (10-140) days. 14 patients died (1 patient died of non-reconstitution of hematopoiesis, 2 patients died of cerebral hemorrhage, 4 patients died of infection and 7 patients died of relapse). The incidence of II-IV aGVHD,Moderate to severe cGVHD,cytomegalovirus viremia and invasive fungal disease (IFD) is similar between Dec+FB3 group and control group (4.2% vs 11.5% in II-IV aGVHD P=0.172,29.6% vs 12.4% in cGVHD P=0.219,14.2% vs 11.5% in cytomegalovirus viremia, p=0.660 and 24.4% vs 24.6% in IFD, p=0.990) . The main adverse reactions during conditioning included dizziness, nausea, vomiting, diarrhea and oral ulcer. Symptoms were relieved after symptomatic therapy. Transient transaminase increased slightly in 3 patients, and improved after liver protection treatment. The overall tolerance of patients in Dec+FB3 group was better than control group. The 2-year LFS and OS rate in Dec+FB3 group and control group were 71.6 % vs.67.1 % (p=0.6822) and 72.8% vs.69.4% (p=0.4885), respectively. Conclusion In the case that the age of patients in Dec+FB3 group was significantly higher than that in the control group, this study achieved similar therapeutic efficacy between two groups, without increasing transplantation related toxicity. This indicates that Dec+FB3 conditioning regimen is safe and effective for allo-HSCT in elderly/frail AML patients,We will conduct a multi-center, prospective, controlled clinical study to evaluate its efficacy.