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

Abstract

Purpose: Relapse is a major cause of treatment failure after allogeneic hematopoietic stem-cell transplantation (allo-HSCT) for high-risk acute myeloid leukemia (HR-AML). The aim of this study was to explore the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) combined with minimal-dose decitabine (Dec) on the prevention of HR-AML relapse after allo-HSCT.

Patients and methods: We conducted a phase II, open-label, multicenter, randomized controlled trial. Two hundred four patients with HR-AML who had received allo-HSCT 60-100 days before randomization and who were minimal residual disease negative were randomly assigned 1:1 to either rhG-CSF combined with minimal-dose Dec (G-Dec group: 100 µg/m² of rhG-CSF on days 0-5 and 5 mg/m² of Dec on days 1-5) or no intervention (non-G-Dec group). The primary outcome was relapse after transplantation, and the secondary outcomes were chronic graft-versus-host disease (cGVHD), safety of the treatment, and survival.

Results: The estimated 2-year cumulative incidence of relapse in the G-Dec group was 15.0% (95% CI, 8.0% to 22.1%), compared with 38.3% (95% CI, 28.8% to 47.9%) in the non-G-Dec group (P < .01), with a hazard ratio (HR) of 0.32 (95% CI, 0.18 to 0.57; P < .01). There was no statistically significant difference between the G-Dec and non-G-Dec groups in the 2-year cumulative incidence of cGVHD without relapse (23.0% [95% CI, 14.7% to 31.3%] and 21.7% [95% CI, 13.6% to 29.7%], respectively; P = .82), with an HR of 1.07 (95% CI, 0.60 to 1.92; P = .81). After rhG-CSF combined with minimal-dose Dec maintenance, increasing numbers of natural killer, CD8+ T, and regulatory T cells were observed.

Conclusion: Our findings suggest that rhG-CSF combined with minimal-dose Dec maintenance after allo-HSCT can reduce the incidence of relapse, accompanied by changes in the number of lymphocyte subtypes.

FIG 1.

Flowchart of the study participants. (*) Observation was stopped according to the visit schedule, and only disease status and survival of the patients were followed. cGVHD, chronic graft-versus-host disease; Dec, decitabine; rhG-CSF, recombinant human granulocyte colony-stimulating factor.

FIG 2.

Cumulative incidence of (A) relapse, (B) total chronic graft-versus-host disease (cGVHD), and (C) cGVHD without relapse. G-Dec, recombinant human granulocyte colony-stimulating factor plus decitabine; HR, hazard ratio.

FIG 3.

Changes in the mean absolute counts of lymphocyte subsets after recombinant human granulocyte colony-stimulating factor (rhG-CSF) plus decitabine (Dec) maintenance treatment (G-Dec group). The number of patients in both the G-Dec group and the non–G-Dec (no treatment) control group was 20. (A) Natural killer (NK) cells. (B) CD19+ B cells. (C) CD3+CD4+ T cells. (D) CD3+CD8+ T cells. (E) CD4+CD25+FOXP3+ T cells. (*) After Bonferroni correction, P < .001 v non–G-Dec group. C, cycle; C1D1, first day in the first cycle before medication; D, day; K, thousand; Treg, regulatory T cell.

FIG 4.

(A) Leukemia-free survival and (B) overall survival among the patients in the two groups. G-Dec, recombinant human granulocyte colony-stimulating factor plus decitabine; HR, hazard ratio.

FIG A1.

Forest plot summarizing hazard ratios for the G-Dec group versus the non-G-Dec group in the subgroup analyses with a test for interaction. ACNU, nimustine; Ara-C, cytarabine; ATG, thymoglobulin; BU, busulfan; CR_MRD−, complete remission and minimal residual disease negative; CY, cyclophosphamide; HSCT, hematopoietic stem-cell transplantation.