The Proportional Relationship Between Pretransplant WT1 mRNA Levels and Risk of Mortality After Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia Not in Remission

Transplantation. 2019 Oct;103(10):2201-2210. doi: 10.1097/TP.0000000000002662.

Abstract

Background: The relationship between the expression levels of Wilms' tumor-1 gene (WT1) mRNA in peripheral blood before allogeneic hematopoietic cell transplantation (allo-HCT) and risk of mortality in acute myeloid leukemia (AML) patients in noncomplete remission (non-CR) remains quite elusive.

Methods: We retrospectively assessed the impact of the pretransplant WT1 mRNA level on survival after allo-HCT in non-CR AML patients.

Results: A total of 125 AML patients, including 46 non-CR patients (36.8%), were analyzed. On multivariate analysis of non-CR AML patients, WT1 mRNA ≥5000 copies/μg RNA was significantly related to increased risk of mortality (hazard ratio, 2.7; 95% confidence interval, 1.3-5.5; P = 0.008). Furthermore, in the entire cohort, log10-transformed WT1 mRNA before allo-HCT was found to be significantly associated with the increased risk of mortality irrespective of whether the disease status was CR or non-CR, using Akaike's information criterion. As the pretransplant WT1 mRNA level elevated, the hazard ratio of mortality monotonically increased in a nonlinear manner regardless of remission status, suggesting that WT1 mRNA level in peripheral blood might reflect tumor burden.

Conclusions: This study demonstrated that the pretransplant WT1 mRNA level was a powerful prognostic factor in allo-HCT even for non-CR AML patients, and there may be a WT1 mRNA threshold in non-CR patients for benefiting from allo-HCT.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Kaplan-Meier Estimate
  • Leukemia, Myeloid, Acute / blood
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / surgery*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / epidemiology*
  • Preoperative Period
  • Prognosis
  • RNA, Messenger / blood
  • Reference Values
  • Retrospective Studies
  • Transplantation, Homologous / adverse effects
  • WT1 Proteins / blood*
  • WT1 Proteins / genetics
  • Young Adult

Substances

  • Biomarkers, Tumor
  • RNA, Messenger
  • WT1 Proteins
  • WT1 protein, human