Clinical relevance of bcl-2(MBR)/JH rearrangement detected by polymerase chain reaction in the peripheral blood of patients with follicular lymphoma

Abstract

Summary We evaluated the prognostic role of peripheral blood polymerase chain reaction (PCR) assay for detection of the bcl-2(MBR)/JH rearrangement in 59 patients with follicular lymphoma (FL) treated at our centre since 1989. Thirty-five (59%) patients were bcl-2/JH positive and 24 (41%) were negative in the peripheral blood at diagnosis. Peripheral blood bcl-2/JH rearrangement detection at diagnosis had no relation to overall survival (OS) and time to progression (TTP). Peripheral blood PCR assay was performed post treatment in 17 patients who were bcl-2/JH positive at diagnosis. Fourteen of the patients (82%, 95% Cl 56-96%) became bcl-2/JH negative. Nine of these patients were further analysed during follow-up and, after several months, circulating cells carrying the bcl-2/JH rearrangement reappeared in five of the nine patients. Peripheral blood clearance of bcl-2/JH-positive cells was correlated with better overall survival (log-rank P < 0.05) but not with TTP.Our data confirmed that bcl-2(MBR)/JH rearrangement detection by PCR at diagnosis is not a prognostic factor in follicular lymphoma. In our series, clearance of circulating bcl-2/JH-positive cells appeared to correlate with better overall survival. Post-treatment examination of the peripheral blood by PCR may have clinical relevance for prediction of the survival pattern of the patients.

Absence of the t(14;18) chromosomal translocation in primary cutaneous B-cell lymphoma

“…This may be important in PCBCL, where the tumour population may be small and therefore the t(14;18) translocation may be below the threshold of detection using Southern blot analysis 26 . The method of choice now used by most groups in nodal systemic disease is nested PCR, 29–31 which increases the sensitivity of the technique but can reduce specificity. We used a single‐round PCR reaction incorporating radioactively labelled nucleotides to increase the specificity, in combination with a high resolution and sensitive electrophoretic technique employing denaturing polyacrylamide gels.…”

“…Although useful in diagnosis, and in the detection of minimal residual disease following treatment, 29,30 the clinical significance of this translocation remains controversial. Its presence has been correlated with a range of clinical outcomes in different studies 31,32 . The t(14;18) translocation can be detected at very low levels in healthy indivividuals 33 and in non‐lymphoid diseases in which it does not predispose to malignancy 34 …”

The differentiation of idiopathic inflammatory pseudotumor from lymphoid tumors of orbit: Analysis of 319 cases

“…In contrast, a polyclonal population such as idiopathic orbital inflammatory pseudotumor will yield a diffuse and smeared pattern or no band on a gel owing to the large number of fragments of varying sizes. [13][14][15][16][17][18][19][20][21][22][23][24] Fifteen out of 20 malignant lymphoma patients in our study were diagnosed as monoclonal by PCR, illustrating that this approach is useful in differentiating benign from malignant lymphoma. However, it should bear in mind that negative results do not mean benign or polyclonality.…”

Insights into the molecular pathogenesis of follicular lymphoma arising from analysis of geographic variation

“…[121][122][123] Historically, the use of conventional alkylating agents or anthracycline-based chemotherapy does not produce CMR, even in patients with complete clinical response rates of more than 80%. 57,87,[124][125][126] However, novel treatments that include fludarabinebased combination regimens and the monoclonal antibody rituximab have been associated with substantial CMR rates. 121,123 Similarly, results of in vitro autologous stem cell purging to produce bcl-2 PCR negativity have also demonstrated encouraging results.…”