title: 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 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.
authors.affiliation: Department of Hematology and Oncology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. ttoubai@hkg.odn.ne.jp
authors.forename: Tomomi
authors.initials: T
authors.lastname: Toubai
authors.forename: Junji
authors.initials: J
authors.lastname: Tanaka
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ota
authors.forename: Takashi
authors.initials: T
authors.lastname: Fukuhara
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hashino
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kondo
authors.forename: Masaharu
authors.initials: M
authors.lastname: Kasai
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Kakinoki
authors.forename: Nobuo
authors.initials: N
authors.lastname: Masauzi
authors.forename: Masanobu
authors.initials: M
authors.lastname: Morioka
authors.forename: Tsugumichi
authors.initials: T
authors.lastname: Kawamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwasaki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Asaka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Imamura
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002999:Clone Cells; D005260:Female; D005500:Follow-Up Studies; D015321:Gene Rearrangement; D015329:Gene Rearrangement, T-Lymphocyte; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D018365:Neoplasm, Residual / Q000175:diagnosis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality; D012074:Remission Induction; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D007143:Immunoglobulin Heavy Chains