The clinical significance of molecular response in indolent follicular lymphomas

Armando López-Guillermo, Fernando Cabanillas, Peter McLaughlin, Terry Smith, Fredrick Hagemeister, María A. Rodríguez, Jorge E. Romaguera, Anas Younes, Andreas H. Sarris, H. Alejandro Preti, William Pugh, Ming Seng Lee

Research output: Contribution to journalArticle

149 Scopus citations

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, β2-microglobulin (β2-M; P < .01), and molecular response (P < .001) were the most important variables associated with outcome. When we combined β2-M and molecular response, three prognostic groups emerged: (1) low β2-M and molecular responders, (2) low β2-M and nonresponders or high β2-M and responders, and (3) high β2-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 β2- M.

Original languageEnglish (US)
Pages (from-to)2955-2960
Number of pages6
JournalBlood
Volume91
Issue number8
DOIs
StatePublished - Apr 15 1998

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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