The significance of molecular response of follicular lymphoma to central lymphatic irradiation as measured by polymerase chain reaction for t(14;18)(q32;q21)

Backgound: More than 80% of the patients with follicular lymphoma have a ch aracteristic chromosomal translocation, t(14;18)(q32;q21), at the major bre akpoint region (MBR) or minor cluster region (MCR) involving the bcl-2 onco gene, This study was undertaken to assess the significance of the molecular response rate measured by the polymerase chain reaction (PCR) evidence of translocation among patients with Stage I to III follicular lymphoma treate d with central lymphatic irradiation (CLI), Methods and Materials: Thirty-three patients with Stage I-III follicular ly mphoma were treated with CLI on a prospective protocol, Bone marrow and per ipheral blood samples were obtained before CLI for PCR analysis of t(14;18) (q32; q21), PCR-positive patients were followed by PCR analysis at regular intervals during and after CLI, and the results were correlated with clinic al outcome. The following pretreatment factors were also investigated for t heir relationship to relapse and molecular response: gender, age, lactate d ehydrogenase (LDH) and beta -2 microglobulin (beta2 M) levels, Ann Arbor st age, and International Prognostic Index (IPI) for malignant lymphoma. Results: The subjects were 19 men and 14 women, with a median age of 52 yea rs (range 30-69), who started CLI between January 1993 and February 1998, M edian follow-up was 44 months (range 12-67), and all but 2 patients were st ill alive at the last follow-up. Four patients were Stage IA, 8 were Stage IIA, 19 were Stage IIIA, and 2 were Stage IIIB, Two patients had abnormal L DH levels (> 618 U/dL) and 7 patients had abnormal beta 2M levels (> 2 mg/d L), Nine patients had IPI = 0, 16 had IPI = 1, and 8 had IPI = 2, All patie nts achieved complete response (CR). Twelve patients have relapsed to date. The median overall time to relapse was 54 months. The actuarial proportion of patients free from relapse at 3 years was 87% (95% confidence interval [CI] 69-95%), A total of 287 PCR results were available, 64 from bone marro w and 223 from peripheral blood. Pretreatment PCR data were available for 2 7 patients, of whom 21 were positive and 3 were unambiguously negative tin blood and bone marrow for both MBR and MCR), For the 19 PCR positive patien ts for whom we had post-treatment results, there was a clear and steady dec reasing trend toward Loss of PCR positivity (49% positive for bone marrow a nd 32% positive for peripheral blood at 3 years). There was a clear trend f or increasing PCR positivity with increasing IPI: 10% for IPI = 0, 31% for IPI = 1, and 63% for IPI = 2 at 3 years for blood. The same trend was also observed for bone marrow. The IPI was the only statistically significant pr edictor for relapse with a relapse-free survival of 91% at 3 fears for IPI < 2 and 75% for IPI = 2 (p = 0.024, log-rank test). Conclusion: Molecular response to CLI occurs gradually over years. High IPI is a negative predictor for molecular response and relapse-free survival. (C) 2001 Elsevier Science Inc.