Rearrangement Patterns of Igs and bcl2/IgH and Clinical Significance in Follicular Lymphoma.

Objectives: To identify a clonal population by molecular techniques in patients treated with Fluradabine, Cyclophosphamide, Rituximab (CF+R) and included in the LNF-03 clinical trial. To relate these alterations to the clinical variables at diagnosis and response to treatment.

Patients and Methods: Patients: 71 patients from the LNF-03 clinical trial. Their treatment consisted of CF+ Rx6 and posterior maintenance with Rituximab. Peripheral Blood (PB) and Bone Marrow (BM) were studied at diagnosis.

Methods: bcl2/IgH rearrangements were studied by real-time PCR (Olsson et al, Mod Pathol 1999). Ig rearrangement of VDJ IgH, Igs IgL KVJ, Kdel and LVJ was studied according to BIOMED II protocols.

Results: 43 of the 71 patients (60.56%) presented some molecular alteration in PB or BM. 33% of the patients in the study presented t(14;18) in some of its majority forms, bcl2/IgH mayor 19 (26.4%) and minor 3 (4.22%). 13 patients were positive for bcl-2/IgH, both in BM and in PB. The median amount of blc2/IgH in BM was 8.315% (62.9–0.04), Whereas in pb it was 4.775% (92.6–0.06), with no significant differences observed. Nevertheless, monoclonality was detected in BM in eight cases but not in PB, and to the inverse, one it happened in three patients.

Of 71 patients, 38 (53.52%), presented displayed monoclonality in at least one of the Ig genes. Of these patients, 38% presented the clonal rearrangement in IG-L KVJ, 26% in IG-H CDR1, 23% in IG-L KDEL, and 13% rearranged in IG-L LAMBDA. There were 57 patients whose BM was available. 28 of them presented pathological infiltration, and monoclonality was detected in 23 cases; in 29 patients who were not pathologically infiltrated, monoclonality was detected in 12 cases. 83% (6/37) of the patients presented a complete response (CR), 8.1% (3/37) uncertain CR (uCR) and 8.1% (3/37) partial response (PR), after the induction treatment.

No relation was found between the presence of molecular alterations in BM/PB and the achievement of a CR.

Conclusions: The study of the rearrangements of Ig and bcl2/IgH is a good strategy for identifying lymphomatosus disease at diagnosis; bone marrow is more informative than peripheral blood. The presence of molecular alterations in PB and/or BM is not related to a poorer answer to induction treatment. Partially funded by Roche Farma SA.