Preemptive low-dose interleukin-2 or DLI for late-onset minimal residual disease in acute leukemia or myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation

Ann Hematol. 2021 Feb;100(2):517-527. doi: 10.1007/s00277-020-04326-6. Epub 2020 Oct 31.

Abstract

Minimal residual disease (MRD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) heralds high risk of relapse. Whether preemptive recombinant interleukin-2 (pre-IL2) is effective for patients with late-onset MRD (LMRD) remains unknown. We retrospectively compared the efficacy and safety of pre-IL2 (n = 30) and pre-DLI (n = 25) for LMRD in patients receiving allo-HSCT for acute leukemia or myelodysplastic syndrome. The 1-year overall survival (OS) and disease-free survival (DFS) rates were 86.7% and 78.4% (P = 0.267), 83.3% and 75.6% (P = 0.329), the cumulative incidence of grades III-IV acute graft-versus-host disease (aGVHD) at 100 days post-preemptive intervention was 3.3% and 12.0% (P = 0.226) in the pre-IL2 group and pre-DLI group, respectively. The 1-year cumulative incidence of moderate/severe chronic GVHD (cGVHD), relapse (CIR), and non-relapse mortality (NRM) were 7.7% and 27.9% (P = 0.018), 13.6% and 20.0% (P = 0.561) and 3.3% and 5.5% (P = 0.321) in the two groups, respectively. No remarkable differences in CIR, OS, and DFS between the two intervention groups were found in multivariate analysis. The GVHD-free and relapse-free survival (GRFS) were better in the pre-IL2 group than in the pre-DLI group (HR = 0.31, 95% confidence interval (CI), 0.12-0.76; P = 0.011). In conclusion, preemptive low-dose IL2 and preemptive DLI yield comparable outcomes for patients with LMRD receiving allo-HSCT, in terms of aGVHD, NRM, relapse, OS, and DFS. However, preemptive low-dose IL2 has a lower incidence of moderate/severe cGVHD and a higher CRFS. Preemptive low-dose IL2 may be an alternative method for patients who develop LMRD after allo-HSCT, particularly for patients who cannot receive preemptive DLI.

Keywords: Allogeneic stem cell transplantation; Donor lymphocyte infusion; Interleukin-2; Minimal residual disease; Preemptive.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Allografts
  • Child
  • Chronic Disease
  • Disease-Free Survival
  • Female
  • Graft vs Host Disease* / blood
  • Graft vs Host Disease* / mortality
  • Graft vs Host Disease* / prevention & control
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Incidence
  • Interleukin-2 / administration & dosage*
  • Leukemia* / blood
  • Leukemia* / mortality
  • Leukemia* / therapy
  • Lymphocyte Transfusion*
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes* / blood
  • Myelodysplastic Syndromes* / mortality
  • Myelodysplastic Syndromes* / therapy
  • Neoplasm, Residual
  • Retrospective Studies
  • Survival Rate

Substances

  • IL2 protein, human
  • Interleukin-2