Minimal residual disease (MRD) monitoring using rearrangement of T-cell receptor and immunoglobulin H gene in the treatment of adult acute lymphoblastic leukemia patients

Am J Hematol. 2005 Nov;80(3):181-7. doi: 10.1002/ajh.20461.

Abstract

We evaluate whether molecular monitoring of minimal residual disease (MRD) using TCR delta (TCRD), TCR gamma (TCRG), and immunoglobulin H (IgH) gene rearrangements in the bone marrow (BM) is correlated with clinical events in ALL patients. The 14 patients enrolled in this study included 6 males and 8 females with a median age of 53 years (range, 25-79 years), and the median duration of follow-up was 417 days (range, 57-617 days). The median WBC count was 11.3 x 10(9)/L at diagnosis. All patients had L2 type ALL. Eleven patients had a monoclonal pattern of IgH (7), TCRD (3) and TCRG (1), and 3 patients had two clonal patterns. Eleven of the 14 patients achieved the first complete remission (CR) after the first induction chemotherapy. We analyzed 9 of 11 CR patients who could be examined immediately after induction chemotherapy (including re-induction therapy). Event-free survival (EFS, 0%) and disease-free survival (DFS, 0%) at 1 year in CR patients with MRD level >or=10(-3) (n = 3) were significantly lower than those in CR patients with MRD level <10(-3) (n = 6) (log-rank test, P = 0.013, 0.013). A lower MRD in BM value after induction chemotherapy was associated significantly with longer survival in the log-rank test. Our data provide evidence that molecular MRD status of BM is a strong predictor of outcome in adult ALL.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Clone Cells
  • Female
  • Follow-Up Studies
  • Gene Rearrangement*
  • Gene Rearrangement, T-Lymphocyte*
  • Gene Rearrangement, delta-Chain T-Cell Antigen Receptor
  • Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor
  • Humans
  • Immunoglobulin Heavy Chains / genetics*
  • Male
  • Middle Aged
  • Molecular Diagnostic Techniques
  • Neoplasm, Residual / diagnosis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Remission Induction
  • Survival Analysis

Substances

  • Antineoplastic Agents
  • Immunoglobulin Heavy Chains