Correlation of bcl-2 rearrangement with clinical characteristics and outcome in indolent follicular lymphoma

The t(14;18) translocation, which involves the bcl-2 oncogene, occurs in fo llicular lymphomas (FL) at two common sites: the major breakpoint region (M BR) and the minor cluster region (mcd. The biological and clinical signific ance of these breakpoints is unknown. The bcl-2 breakpoint site was determi ned in 247 previously untreated patients (49% men; median age 52 years) wit h indolent FL (155 grade 1, 83 grade II, and 8 grade III) to correlate it w ith pretreatment characteristics, response, and outcome. The bcl-2 breakpoi nt site was determined by a polymerase chain reaction method of peripheral blood tall cases), bone marrows (149 cases), and fresh lymph node biopsy sp ecimens (68 cases). The breakpoint site occurred at MBR in 175 cases (71%) and at mcr in 27 (11%). In 45 cases (18%), no breakpoint was detected (germ line). No significant relationship was found between the rearrangements and the expression of BLC-2 and BAX proteins. Patients' germline for MBR and m cr tended to present more frequently with stage IV disease and higher beta 2-microglobulin (beta 2M) levels, whereas mcr-rearranged patients presented more frequently with early stage and normal beta 2M. The complete response rate of germline patients was significantly lower than that of MBR and mcr patients, An estimated 3-year failure-free survival (FFS) for mcr, MBR, an d germline cases was 95%, 76%, and 57%, respectively (P < .001). The bcl-2 breakpoint site was independent of serum beta 2M and lactate dehydrogenase in its correlation with FFS. In conclusion, the bcl-2 rearrangement site is an important prognostic factor in indolent FL, useful to identify patients who may require different treatment. (C) 1999 by The American Society of H ematology.