Rapid and Sustained Clearance of Circulating Lymphoma Cells after Chemotherapy Plus Rituximab: Clinical Significance of Quantitative T(14;18) PCR Monitoring in Advanced Stage Follicular Lymphoma Patients†

SummaryThis study of first‐line treatment in advanced‐stage follicular lymphoma patients analysed the effects of MCP (mitoxantrone, chlorambucil and prednisolone) chemotherapy alone or in combination with rituximab (R‐MCP) on circulating lymphoma cells (CLC) and assessed the prognostic value of a quantitative monitoring of CLC. CLC numbers were determined by quantitative polymerase chain reaction (PCR) for the t(14;18)‐translocation or by allele‐specific PCR for rearranged immunoglobulin heavy chain genes. We analysed blood samples from 43 patients treated in a randomized trial comparing eight cycles of MCP versus R‐MCP. Clearance of CLC at the end of therapy was achieved in 21/25 patients (84%) treated with R‐MCP compared with 0/18 after MCP alone (P < 0·0001). A ≥2 log CLC reduction was associated with a favourable clinical response (P = 0·0004) and prolonged event‐free survival (P = 0·02). In R‐MCP patients, stable CLC numbers or consistently PCR‐negative blood samples were associated with a continuing clinical remission whereas in two patients a relapse was preceded by a ≥2 log CLC increase. This study demonstrated that R‐MCP led to a rapid and sustained eradication of CLC and a ≥2 log CLC reduction was associated with a superior quality and duration of the clinical response.