Recombinant human granulocyte colony-stimulating factor (rhG-CSF) combined with minimal-dose decitabine may reduce the incidence of relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with high-risk acute myeloid leukemia (AML), according to research published in the Journal of Clinical Oncology.
The current best survival rates for high-risk AML patients undergoing allo-HSCT after achieving complete remission (CR) is 55%. Relapse remains a problem, and is the leading cause of death for these patients after transplantation.
An open-label, multicenter, randomized, controlled phase 2 trial evaluated whether rhG-CSF with minimal-dose decitabine can help prevent relapse in this patient population.
A total of 204 patients from 12 transplant centers in China were randomly assigned (1:1) to the rhG-CSF plus decitabine (G-Dec) group or to the observation group, which received no treatment. Patients in the G-Dec group were administered 100 μg/m2 of rhG-CSF on days 0 to 5 and 5 mg/m2 of decitabine on days 1 to 5 every 6 to 8 weeks for up to 6 courses. The primary outcome measured relapse following transplantation, and the secondary outcomes included graft-vs-host disease (GVHD), treatment safety, and survival.
After a median follow-up of 28 months in the G-Dec group, 15 of the 100 patients who received treatment relapsed. At a median follow up of 26.4 months in the observation group, 39 of 102 patients had relapsed.
Patients with complete remission and minimal residual disease (MRD) negativity had a decreased relapse rate after the G-Dec treatment. The authors suggest this maintenance treatment may have more benefit for patients who are MRD negative before allo-HSCT.
The 2-year leukemia free survival rate in the G-Dec group was 81.9% compared with 60.7% in the observation group (P <.01). The 2-year overall survival (OS) was 85.8% in the G-Dec group vs 69.7% in the observation group (P =.01).
Despite treatment-related adverse events, 96% of patients completed all 6 cycles of rhG-CSF plus minimal-dose decitabine. A total of 34 patients in the treatment group and 49 patients in the observation group developed chronic GVHD.
The authors suspected that the G-Dec maintenance regimen reduces relapse by increasing the number of natural killer cells and CD8+ T cells. In the study, some patients had an increase in T regulatory cells after the second treatment cycle. This may account for why patients in the G-Dec group did not have an increased incidence of chronic GVHD after transplantation.
Study limitations included the small sample size of subgroups and the open-label design. The authors concluded that rhG-CSF with minimal-dose decitabine can reduce the incidence of relapse in patients with high-risk AML.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Gao L, Zhang Y, Wang S, et al. Effect of rhG-CSF combined with decitabine prophylaxis on relapse of patients with high-risk MRD-negative AML after HSCT: an open-label, multicenter, randomized controlled trial. J Clin Oncol. Published online October 27, 2020. doi:10.1200/JCO.19.03277