Detection of Minimal Residual Disease by bcl-2 PCR in Early Stage Follicular Lymphomas

The polymerase chain reaction (PCR) assay provides a powerful means of detecting minimal residual disease in follicular lymphoma. Most available data, however, are on stage IV cases.

We tested the blood of 86 patients with stage I-III previously untreated follicular lymphoma before and after therapy with three objectives: (1) to determine the frequency of positive PCR at diagnosis; (2) to examine the correlation of molecular response (conversion to negative PCR in blood) with clinical outcome; and (3) to evaluate the molecular response rate of three different treatment approaches. These consisted of: (1) central lymphatic radiation (mantle plus whole-abdominopelvic radiation) in 23 patients; (2) COP (cyclophosphamide, Oncovin, and prednisone)/CHOP (cyclophosphamide, doxorubicin HCl, Oncovin, and prednisone) with or without involved-field radiation in 43 patients; and (3) chemotherapy alone with an intensive regimen (three alternating combinations [“ATT”]) in 20 patients.

Of 86 patients tested at baseline for both mbr and mcr breakpoints, 74 (86%) were positive in blood. The table below shows the projected failure-free survival (FFS) at 7 years according to the molecular response at 3, 6, and 12 months during therapy:

CONCLUSION: (1) In spite of localized stage, most cases had circulating bcl-2 rearranged cells. (2) Radiation, although a local treatment, resulted in a relatively high systemic molecular response rate. (3) Achievement of early molecular response (3 months) correlated best with clinical outcome. (4) ATT induced a significantly higher molecular response at 3 months, as compared with COP/CHOP with or without radiation.

Click here for Dr. Bruce Cheson’s commentary on this abstract.