Stage I/II follicular lymphoma: spread of bcl‐2/IgH+ cells in blood and bone marrow from primary site of disease and possibility of clearance after involved field radiotherapy

Abstract

Summary Stage I/IIA follicular lymphoma (FL) is considered a localised disease that can be adequately treated with radiotherapy alone. Bone marrow (BM) and peripheral blood (PB) involvement in FL was investigated by polymerase chain reaction (PCR) in a series of 24 consecutive patients with histologically revised diagnosis and treated with involved field radiotherapy. Despite the limited stage, Bcl‐2/IgH+ cells were found at diagnosis in PB and/or BM of 16 patients (66·6%). After treatment, in 9/15 Bcl‐2/IgH positive evaluable patients, a disappearance of Bcl‐2/IgH+ cells was observed, which persisted after a median follow‐up of 43·5 months (range 11–70) in all but one patient. Quantitative PCR demonstrated the feasibility of clearing PB and BM Bcl‐2+ cells after local irradiation of the primary site of the disease only when the basal number of lymphoma cells was <1:100 000. Patients with Bcl‐2/IgH+ cells at diagnosis or after treatment had a higher likelihood of relapse. Thus, despite a negative BM biopsy, the majority of localised FL Bcl‐2/IgH+ cells were found in the PB and BM. Lymphoma cells can reversibly spread from the affected lymph node to PB and BM and, in a proportion of cases, durably disappear after irradiation. The possibility of a persistent lymphoma cell clearance is proportional to the amount of cells detected at presentation by quantitative PCR.

Bcl-2/IgH expression in minimal bone marrow infiltration by follicular lymphoma cells

“…It has been reported that 88.5% of bcl-2/IgH rearrangements occur at the MBR breakpoint (7). The results suggest a higher rate of BM infiltration than other studies (8)(9)(10).…”

Nodal Follicular Lymphoma

“…[25]. However, quantitative PCR demonstrated the feasibility of clearing PB and BM bcl-2 + cells after IFI of the primary site of disease: as a consequence of the elimination of the primary focus, characteristic tumor cell contaminations of PB/BM were absent after treatment in the majority of patients [43].…”

R-CHOP therapy alone for limited-stage follicular lymphoma

“…Other investigators [15] have reported that 4 of 4 (100%) CS1 FL and 12 of 20 (60%) CS2 FL cases showed PCR positivity for the Bcl-2/IgH rearrangement in PB and/or BM samples prior to treatment. All of them received irradiation therapy and post-treatment molecular evaluation was performed in 15 of the 16 PCR-positive patients.…”