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

Abstract

We evaluate whether molecular monitoring of minimal residual disease (MRD) using TCR d (TCRD), TCR g (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 · 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 ‡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 logrank test. Our data provide evidence that molecular MRD status of BM is a strong predictor of outcome in adult ALL. Am.

Cross-sectional monitoring of Wilms' tumor gene 1 (WT1) expression in Iranian patients with acute lymphoblastic leukemia at diagnosis, relapse and remission

“…Therefore, molecular tests with high sensitivity and specificity like PCR are being used for quantitative estimation of residual disease. There are some useful markers for detection of MRD by molecular methods such as immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements [3], as well as certain chromosomal rearrangements [4]. Most of the above molecular markers have some limitations and investigators try to find the best marker for detection of MRD in specific cancers.…”

The TCR γδ Repertoire and Relative Gene Expression Characteristics of T-ALL Cases with Biclonal Malignant Vδ1 and Vδ2 T Cells

“…However, confirmation by FACS using specific Vd subfamily antibodies, which can directly show the percentage of malignant T-cell clones, is needed. Thus, these malignant T-cell clones may at least serve as biomarkers for the detection of minimal residual disease (MRD) (Kode et al, 2004;Toubai et al, 2005).…”

How and why minimal residual disease studies are necessary in leukemia: a review from WP10 and WP12 of the European LeukaemiaNet

“…[83][84][85][86] Available data imply that low molecular MRD after induction is a good prognostic factor in pediatric ALL, independent of other clinically relevant risk factors, such as age, blast count, immunophenotype, chromosomal aberrations at diagnosis and response to prednisone. Furthermore, investigators report that patients who relapse after remission and are again subjected to re-induction therapy have event free survival rates of 86% and 0% among those determined to have MRD levels of <1×10 -3 and ≥1×10 -3…”