Prognostic impact of pretransplant measurable residual disease assessed by peripheral blood WT1-mRNA expression in patients with AML and MDS

Eur J Haematol. 2021 Aug;107(2):283-292. doi: 10.1111/ejh.13664. Epub 2021 May 27.

Abstract

Objective: As peripheral blood (PB) Wilm's Tumor 1 (WT1)-mRNA expression is established as MRD-marker during conventional AML chemotherapy, impact of pretransplant WT1 expression remains unclear. Therefore, we aimed to assess prognostic impact of pretransplant WT1 expression on post-transplant outcome in patients with AML/MDS.

Methods: In 64 AML/MDS patients, pretransplant WT1 expression was retrospectively analyzed using a standardized assay offering high sensitivity, specificity, and a validated cut-off. Patients were divided into three groups determined by pretransplant remission and WT1 expression. Post-transplant outcome of these groups was compared regarding cumulative incidence of relapse (CIR), relapse-free (RFS), and overall survival (OS).

Results: Pretransplant forty-six patients (72%) showed hematologic remission, including 21 (46%) MRD-negative and 25 (54%) MRD-positive patients indicated by WT1 expression, while 18 refractory patients (28%) showed active disease. Two-year estimates of post-transplant CIR, RFS, and OS were similar in MRD-positive (61%, 37%, 54%) and refractory patients (70%, 26%, 56%), but significantly inferior compared with MRD-negative patients (10%, 89%, 90%). After multivariable adjustment, pretransplant MRD negativity measured by WT1 expression retained its prognostic impact on CIR (P = .008), RFS (P = .005), and OS (P = .049).

Conclusions: PB WT1 expression represents a useful method to estimate pretransplant MRD, which is highly predictable for post-transplant outcome and may help improving peri-transplant management in AML/MDS patients.

Keywords: WT1; acute myeloid leukemia; measurable residual disease; myelodysplastic syndrome; relapse; transplantation.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor*
  • Blood Cells
  • Cell-Free Nucleic Acids
  • Female
  • Gene Expression
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / mortality*
  • Leukemia, Myeloid, Acute / pathology
  • Leukemia, Myeloid, Acute / therapy
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / mortality*
  • Myelodysplastic Syndromes / pathology
  • Myelodysplastic Syndromes / therapy
  • Neoplasm, Residual / diagnosis
  • Neoplasm, Residual / genetics*
  • Preoperative Period
  • Prognosis
  • RNA, Messenger
  • Recurrence
  • Retrospective Studies
  • Transplantation, Homologous
  • Treatment Outcome
  • WT1 Proteins / genetics*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Cell-Free Nucleic Acids
  • RNA, Messenger
  • WT1 Proteins
  • WT1 protein, human