Correlation of Peripheral Blood Involvement Measured by Four-Color Flow Cytometry and the Achievement of Molecular Response in Mantle Cell Lymphoma Treated within the Prospectively Randomized Intergroup Trials of the European MCL Network

Two prospectively randomized intergroup trials of the European MCL Network investigating the impact of different combined immuno-chemotherapy protocols for patients with stage II–IV mantle cell lymphoma (MCL) >< 65 yrs followed by autologous stem cell transplantation (PBSCT) for patients <65 yrs and a rituximab or interferone maintenance treatment for patients >65 yrs are currently performed.

Patients and methods: 180 German patients with diagnostic peripheral blood (PB) involvement detectable by consensus IGH PCR were analysed for t(11;14) translocation by FISH and 4-colour Flow Cytometry (FC) at diagnosis as well as molecular response (MR) by quantitative IGH-RQ-PCR after induction. The results were compared to clinical parameters at diagnosis and PFS.

Results: Patients had a median age of 61 years, an elevated LDH in 37%, B-symptoms in 41% and extranodal involvement in 37%. According to the MIPI risk factor score 26% had an adverse, 34% an intermediate and 40% a good prognosis. PB involvement by MCL was demonstrated in 67% (74/111) by t(11;14) FISH and in 97% (152/156) by FC. Detection of MCL cells by FC in PB did not correlate with clinical parameters as stage, LDH, extranodal involvement or bone marrow infiltration. However, median % of MCL cells measured by FC differed significantly with clinical stage (p<0.0001), LDH (p=0.0096) bone marrow infiltration (<0.0001) and MIPI prognostic index (0.0002). MR after induction treatment was achieved in 60% (60/100) of patients and correlated with BM infiltration at diagnosis (p=0.0117). There was a trend for improved PFS in patients achieving MR (PFS 90% vs. 75% at 15 months after induction) however, the observation time is still too short for definitive evaluation.

Conclusion: FC is highly sensitive for detection of PB involvement in MCL and improves staging accuracy. Achievement of MR might be an early indicator for treatment outcome after immuno-chemotherapy in MCL with the potential of defining prognostic subgroups.