title: The clinical significance of molecular response in indolent follicular lymphomas.
abstract: Most patients with follicular lymphoma (FL) achieve a complete response (CR) after treatment, but eventually most of them, particularly those with stage IV, relapse due to minimal residual disease (MRD). The t(14;18) gives rise to a rearrangement of the bcl-2 oncogene that constitutes an excellent target for detection of MRD by polymerase chain reaction (PCR). One hundred ninety-four previously untreated patients with indolent FL and detectable bcl-2 rearrangement were studied. The PCR assay was used to detect bcl-2-rearranged cells in blood and marrow before and after treatment. Molecular response rate was 37%, 53%, 56%, and 66% at 3 to 5, 6 to 8, 9 to 14, and 15 to 18 months from the start of therapy, respectively. Although molecular response was higher among clinical CRs, one third of partial responders at 3 to 5 months also achieved a molecular response. Patients who achieved a molecular response during the first year of treatment had a significantly longer failure-free survival (FFS) than those who did not (4-year FFS: 76% v 38%, respectively; P < .001). Similar results were also observed in the subset of patients in clinical CR 1 year after treatment. By multivariate analysis, beta2-microglobulin (beta2-M; P < .01), and molecular response (P < .001) were the most important variables associated with outcome. When we combined beta2-M and molecular response, three prognostic groups emerged: (1) low beta2-M and molecular responders, (2) low beta2-M and nonresponders or high beta2-M and responders, and (3) high beta2-M and nonresponders. The 4-year FFS of these 3 groups were 86%, 65%, and 23%, respectively. Finally, patients who achieved molecular response and sustained it had better FFS than those who either reverted back to PCR-positive or who never achieved molecular response. Serial PCR analysis to determine the molecular response in FL correlates well with outcome especially when combined with pretreatment beta2-M.
authors.affiliation: Department of Lymphoma, Laboratory Medicine, University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: A
authors.initials: A
authors.lastname: López-Guillermo
authors.forename: F
authors.initials: F
authors.lastname: Cabanillas
authors.forename: P
authors.initials: P
authors.lastname: McLaughlin
authors.forename: T
authors.initials: T
authors.lastname: Smith
authors.forename: F
authors.initials: F
authors.lastname: Hagemeister
authors.forename: M A
authors.initials: MA
authors.lastname: Rodríguez
authors.forename: J E
authors.initials: JE
authors.lastname: Romaguera
authors.forename: A
authors.initials: A
authors.lastname: Younes
authors.forename: A H
authors.initials: AH
authors.lastname: Sarris
authors.forename: H A
authors.initials: HA
authors.lastname: Preti
authors.forename: W
authors.initials: W
authors.lastname: Pugh
authors.forename: M S
authors.initials: MS
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008224:Lymphoma, Follicular / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D012008:Recurrence; D016019:Survival Analysis
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2