Negative immunomagnetic ex vivo purging combined with high-dose chemotherapy with peripheral blood progenitor cell autograft in follicular lymphoma patients: evidence for long-term clinical and molecular remissions

Abstract

The feasibility and efficacy of a novel immunomagnetic ex vivo negative purging method was evaluated on peripheral blood progenitor cells (PBPC) from 13 non-Hodgkin’s lymphoma patients (eight follicular, FL; three mantle cell, MCL; two FL with histologic transformation). A peculiar feature of the study was the collection of PBPC after prolonged tumor debulking. Our method included a stem cell enrichment phase followed by cell incubation with anti-B cell MoAbs (anti-CD19, CD20, CD22, CD23), addition of immunobeads, and then positive cell removal by passage on a Max-Sep (Baxter Immunotherapy) cell separator. Engraftment was rapid and stable. Hematological values were assessed 1 and 2 years after the autograft. Purging efficacy was molecularly assessed in a panel of 11 patients who showed persistence of PCR-detectable lymphoma cells on PBPC harvests despite intensified chemotherapeutic debulking. PCR-negativity was obtained in vitro and persisted in vivo after autograft in three FL patients; five more FL patients, whose purged PBPC were PCR+, converted to stable (3 patients) or fluctuating (two patients) PCR negativity after autograft. MCL patients never reached PCR negativity. Thus, ex vivo purging may have a role for FL patients harvesting PCR-positive PBPC after intensified chemotherapy. In contrast, the addition of ex vivopurging seems to be of little if any benefit for MCL patients.