Umbilical cord blood microtransplantation improves the prognosis of patients with relapsed/refractory myeloid tumors who are not candidates for intensive therapy: Clinical efficacy and mechanism analysis

Abstract

Abstract Objective: There is no unified standard for the optimal treatment of relapsed/refractory acute myeloid tumors (R/R MN). At present, salvage chemotherapy and hematopoietic stem cell transplantation (HSCT) are mainly used, but most of these patients are not suitable for intensive chemotherapy due to age, physical status, comorbidities and other factors. Cord blood (UCB) has been shown to play a role in hematopoietic reconstruction and graft anti-tumor. The purpose of this study was to explore the clinical efficacy and to analyze the mechanism of cord blood microtransplantation in UNFIT AND R/R MN patients.Methods: A total of 55 patients with ECOG score ≥2 and R/R MN admitted to the Department of Hematology of the Second Hospital of Tianjin Medical University from January 2020 to December 2024 were included in the study (Median age 69 years; Range 26-90 years). They were randomly divided into cord blood microtransplantation group and control group, and all enrolled patients underwent 1 cycle of salvage chemotherapy. The umbilical cord blood micrograft (UCB) group was infused with UCB as adjuvant therapy 1 day after the end of chemotherapy (Total number of MNC (14.45×109, 2-21.81×109); total CD34+ count (3.90×107, 0.93-8.79×107); Percentage of NK cells (1.49%, 0.22-2.48%). Clinical efficacy analysis mainly assesses the overall complete response rate (CR) or complete response with incomplete haematological recovery (CRi). Overall survival (OS), event-free survival (EFS), minimal residual disease (MRD) negativity rate, and blood cell recovery time were used as secondary evaluation indicators. The number of immune cells and cytokine levels were analyzed 28 days after treatment to evaluate the micro-changes in immunity.Results: The median follow-up was 178.5 (1-1505) days. Compared with the control group, 17 patients in the UCB group achieved CR and PR (45.1% vs 33.3%, P=0.026) ORR. The median event-free survival (EFS) was better (P=0.019), the median overall survival was better (P=0.026), the median overall survival was better (P=0.039) in the patients with NR (P=0.039), and the patients with TP53 mutation had better overall survival in the umbilical cord blood adjuvant group (P=0.04). 11 patients in the UCB group achieved MRD negativity (P= 0.026). The median time to neutrophil, hemoglobin and platelet recovery was 22 days (P=0.008), 21 days (P=0.002), and 22 days (P=0.006), respectively. The median recovery time of neutrophils, red eggs and platelets was 22 days (P=0.008), 21 days (P=0.002) and 22 days (P=0.006). No acute graft-versus-host disease (aGVHD) or toxicity-related deaths occurred in any of the patients. At 28 days after microtransplantation, the number of CD3+ T cells, CD8+ effector memory T cells, NK cells and NK Mature cells increased compared with those before reinfusion (P=0.005, P=0.05, P=0.05, P=0.05), and the number of CD19+ B cells decreased (P=0.05). INF-γ level (P=0.05) and TNF-α level increased (P=0.03) at 28 days after microtransplantation.Conclusion: Umbilical cord blood microtransplantation can improve OS and EFS in patients with R/R myeloid tumors who are not suitable for intensive chemotherapy, and reduce the time of hematopoietic reconstruction after chemotherapy. The increase in the proportion of NK and T cells after cord blood microtransplantation improves chemotherapy outcomes by inducing microGVL effects.