Allogeneic HCT for adults with B-cell precursor acute lymphoblastic leukemia harboring IKZF1 gene mutations. A study by the Acute Leukemia Working Party of the EBMT

Bone Marrow Transplant. 2021 May;56(5):1047-1055. doi: 10.1038/s41409-020-01139-z. Epub 2020 Nov 25.

Abstract

The presence of IKZF1 gene mutations is associated with poor prognosis of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The goal of this retrospective study was to evaluate outcome of allogeneic hematopoietic cell transplantation (allo-HCT) in this population. Ninety-five patients transplanted in first (n = 75) or second (n = 20) complete remission (CR) from either HLA-matched sibling (n = 32), unrelated (n = 47) or haploidentical (n = 16) donor were included in the analysis. The probabilities of the overall survival (OS) and leukemia-free survival (LFS) at 2 years were 55% and 47%, respectively. Relapse incidence (RI) was 32% while non-relapse mortality (NRM), 21%. The incidence of grade II-IV acute graft-versus-host disease (GVHD) and chronic GVHD was 34% and 30%, respectively. The probability of GVHD and relapse-free survival (GRFS) was 35%. In a multivariate analysis positive minimal residual disease (MRD) status was associated with decreased chance of LFS (HR = 3.15, p = 0.004) and OS (HR = 2.37, p = 0.049) as well as increased risk of relapse (HR = 5.87, p = 0.003). Disease stage (CR2 vs. CR1) affected all, LFS, OS, GRFS, RI, and NRM. Results of allo-HCT for patients with BCP-ALL and IKZF1 mutations are generally improving, however, individuals with detectable MRD have poor prognosis and require additional intervention prior to transplantation.

MeSH terms

  • Adult
  • B-Lymphocytes
  • Graft vs Host Disease*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Ikaros Transcription Factor / genetics
  • Leukemia, Myeloid, Acute*
  • Mutation
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / therapy
  • Retrospective Studies
  • Transplantation Conditioning

Substances

  • IKZF1 protein, human
  • Ikaros Transcription Factor