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. 2020 Dec 20;38(36):4249-4259. doi: 10.1200/JCO.19.03277. Epub 2020 Oct 27.

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antimetabolites, Antineoplastic / pharmacology
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Child
  • Child, Preschool
  • Decitabine / pharmacology
  • Decitabine / therapeutic use*
  • Female
  • Filgrastim / pharmacology
  • Filgrastim / therapeutic use*
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / therapy*
  • Male
  • Middle Aged
  • Prognosis
  • Recurrence
  • Risk Factors
  • Transplantation Conditioning / methods*
  • Young Adult

Substances

  • Antimetabolites, Antineoplastic
  • Decitabine
  • Filgrastim

Associated data

  • ChiCTR/ChiCTR-IIR-16008182