Elderly patients with acute myeloid leukemia (AML) who are ineligible for allogeneic hematopoietic stem cell transplantation (allo-HSCT) may benefit from umbilical cord blood (UCB) infusion as an adjuvant consolidation therapy. A recent phase 2 study, published in Nature, investigated the efficacy and safety of UCB infusion in combination with chemotherapy in this patient population.
The prospective, single-arm, open-label study enrolled elderly AML patients (age ≥60 years) in complete remission (CR) after one or two cycles of induction therapy. Participants received two cycles of consolidation therapy consisting of low-dose decitabine (15 mg/m2 intravenously for 5 days) and intermediate-dose cytarabine (1.0 g/m2 every 12 hours for 2 days), followed by a single unit of UCB infusion on day 9. The UCB units were matched for at least 4 HLA loci and contained >3 × 107 nucleated cells per kilogram. After consolidation, patients received demethylation treatment as maintenance therapy.
The primary endpoint was overall survival (OS), defined as the time from diagnosis to death. Secondary endpoints included event-free survival (EFS), bone marrow minimal residual disease (MRD), treatment-related adverse events (AEs), and time to neutrophil and platelet recovery. Exploratory analyses involved single-cell RNA sequencing (scRNA-seq) to characterize changes in the immune microenvironment post-UCB infusion.
Clinical Outcomes and Safety
The study demonstrated promising clinical outcomes. The median OS was significantly improved in patients receiving UCB infusion compared to historical controls. The treatment regimen was generally well-tolerated, with manageable hematological and non-hematological AEs. No unexpected safety signals were observed. Early deaths, defined as deaths within 30 days of treatment, were minimal.
Immunomodulatory Effects
ScRNA-seq analysis revealed that UCB infusion induced significant changes in the immune cell composition and function. Notably, there was an increase in the proportion of CD8+ T cells with enhanced cytotoxic potential. These findings suggest that UCB infusion may promote anti-leukemic immunity, contributing to the observed clinical benefits.
Implications for AML Treatment
AML is a heterogeneous hematological malignancy with a poor prognosis, especially in the elderly. While allo-HSCT is the standard of care for eligible patients, many elderly individuals are ineligible due to comorbidities or lack of a suitable donor. This study suggests that UCB infusion represents a feasible and potentially effective consolidation strategy for these patients. The combination of chemotherapy and UCB infusion may offer a valuable treatment option to improve outcomes and quality of life in elderly AML patients who cannot undergo allo-HSCT.
Study Limitations
The study's limitations include its single-arm design and relatively small sample size. Further randomized controlled trials are needed to confirm these findings and to optimize the UCB infusion regimen. Additionally, the lack of targeted therapies used in conjunction with UCB infusion reflects the treatment landscape during the study period, and future research should explore combinations with novel agents.
