Umbilical Cord Blood Microtransplantation in Newly Diagnosed, Elderly Patients with Acute Myeloid Leukemia

Abstract

Objective: We observed the efficacy and safety of umbilical cord blood microtransplantation (UCBMT) in the treatment of newly diagnosed with acute myeloid leukemia (AML) in the elderly.Methods: Prospective one-arm phase I clinical study. The patients should meet the following criteria: 60-80-year-old; newly diagnosed AML; receive the treatment of chemotherapy combined with UCBMT.Result: In total, 11 patients newly diagnosed with AML received chemotherapy in combination with UCBMT, from November, 2019 to January, 2021, including 7 males and 4 females. The average age was 71 (60-80). For the patients, 7 cases with normal chromosome karyotype, and 2 cases with +8 chromosome, 1 case with 7q- chromosome, and 1 case with karyotype of monomer. In the 7 patients with normal chromosome karyotype, 3 cases were FMS-liketyrosine kinease 3 (FLT3) positive (2 of them in combination with nucleophosmin 1 (NPM1) mutation); in addition, in 4 patients of the 7, one showed double mutation of CEBPA, one showed NPM1 mutation, one showed IDH1 mutation, and one showed IDH2 mutation. In 4 patients with chromosomal abnormalities, one patient showed no special gene, one patient showed ASXL1 mutation, one patient was IDH1 mutation, and one patient was TP53 mutation. All of the patients were treated with IA (IDA 8-10 mg/ m 2/day x 3 days, cytarabine 100 mg/ m 2/day x 7 days) for inducing chemotherapy. For the patients with 60-70-year-old, they were treated with IDA (8 mg/ m 2/day); and for the patients with 70-80-year-old, they were treated with darubicin (10 mg/ m 2/day). In the consolidation phase, the patients were treated with cytarabine (1 g/ m 2, q12h) for 3 consecutive days. There were 3 courses of consolidation chemotherapy. Next, patients received single unrelated cord blood transplantation (UCBT) from China's public umbilical cord blood bank, HLA matching was performed for all patients before treatment. A total of 4 units of UCB with HLA 0-3/6（HLA-A,-B,-DR）matching and the ABO blood type matched with the patient were transfused after induction and consolidation chemotherapy for 24-48 hours, then with follow-up. At the same time, the immunological characteristics of these patients were fully analyzed. We demonstrated that, 8 of 11 patients received one course of induction chemotherapy, and achieved a complete response. The complete response rate was 72.7%. What's more, the median time for neutrophils ≥ 0.5 x 10 9/L and platelete ≥ 20 x 10 9/L was 12 days. There were no treatment-related deaths during induction therapy. The median follow-up was 14 (7-31) months. 1 patient showed monomer karyotype with P53 gene mutation, and got complete remission after one course of induction chemotherapy with IA. However, the patient died for AML recurred. For the other 10 patients, they were alive, and the OS of 1 year was 89.8%. Moreover, we found the expression of PD-1 on CD8 +T cells decreased, while the expression of CD38 increased after therapy. Besides, the proportion of NKp30 +NK cells, as well as the IFN-γ +TFN-α +NK cells increased significantly.Conclusion: UCBMT therapy for newly diagnosed elderly AML patients could accelerate the recovery of hematopoietic function and improve the safety of chemotherapy. This method is effective and worthy of further promotion. DisclosuresNo relevant conflicts of interest to declare.