title: Minimal disease assessment in the treatment of children and adolescents with intermediate-risk (Stage III/IV) B-cell non-Hodgkin lymphoma: a children's oncology group report.
abstract: Children/adolescents with mature B-cell non-Hodgkin lymphoma (B-NHL) have an excellent prognosis but relapses still occur. While chromosomal aberrations and/or clonal immunoglobulin (Ig) gene rearrangements may indicate risk of failure, a more universal approach was developed to detect minimal disease (MD). Children/adolescents with intermediate-risk B-NHL were treated with French-British-American/Lymphome Malins de Burkitt 96 (FAB/LMB96) B4 modified chemotherapy and rituximab. Specimens from diagnosis, end of induction (EOI), and end of therapy (EOT) were assayed for MD. Initial specimens were screened for IGHV family usage with primer pools followed by individual primers to identify MD. Thirty-two diagnostic/staging specimens screened positive with primer pools and unique IGHV family primers were identified. Two patients relapsed; first relapse (4 months from diagnosis) was MD-positive at EOI, the second (36 months from diagnosis) was MD-positive at EOT. At EOI, recurrent rates were similar between the MRD-positive and MRD-negative patients (P = 0·40). At EOT, only 13/32 patients had MRD data available with one relapse in the MRD-positive group and no recurrences in the MRD-negative group (P = 0·077). The study demonstrated molecular-disseminated disease in which IgIGHV primer pools could be used to assess MD. This feasibility study supports future investigations to assess the validity and significance of MD screening in a larger cohort of patients with intermediate-risk mature B-NHL.
authors.affiliation: University of Hawaii John A. Burns School of Medicine, 3675 Kilauea Ave., Honolulu, HI 96816, USA. bshirami@hawaii.edu
authors.forename: Bruce
authors.initials: B
authors.lastname: Shiramizu
authors.forename: Stanton
authors.initials: S
authors.lastname: Goldman
authors.forename: Ian
authors.initials: I
authors.lastname: Kusao
authors.forename: Melissa
authors.initials: M
authors.lastname: Agsalda
authors.forename: James
authors.initials: J
authors.lastname: Lynch
authors.forename: Lynette
authors.initials: L
authors.lastname: Smith
authors.forename: Lauren
authors.initials: L
authors.lastname: Harrison
authors.forename: Erin
authors.initials: E
authors.lastname: Morris
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Gross
authors.forename: Warren
authors.initials: W
authors.lastname: Sanger
authors.forename: Sherrie
authors.initials: S
authors.lastname: Perkins
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Cairo
mesh_terms: D000293:Adolescent; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D004812:Epidemiologic Methods; D050438:Genes, Immunoglobulin Heavy Chain; D052138:Genes, Neoplasm; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D018365:Neoplasm, Residual; D012008:Recurrence; D000069283:Rituximab; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab