In Vivo Purging of Circulating CD34+ Progenitor Cells in Low-Grade Lymphoma With Rituximab and High-Dose Chemotherapy

With the aim to overcome the limitations of ex vivo bone marrow purging, we have assessed the ability of the anti-CD20 monoclonal antibody rituximab (Rituxan), given in combination with chemotherapy, to eradicate polymerase chain reaction (PCR)–detectable disease, and to enable the harvesting of large amounts of uncontaminated peripheral blood progenitor cells in patients with low-grade lymphoma (in vivo purging). From April 1997 to July 1998, 20 consecutive patients entered the study. Eligibility included age £ 60 years, a diagnosis of untreated mantle cell lymphoma or of refractory/early relapsed follicular lymphoma, CD20 expression by tumor cells, histologic bone marrow infiltration, and availability of a molecular marker for minimal residual disease detection.

Eligible patients received two to four courses of standard-dose chemotherapy, followed by one course of high-dose cyclophosphamide (Cytoxan, Neosar; 7 g/m²) plus granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim [Leukine, Prokine]) and/or granulocyte colony-stimulating factor (G-CSF, filgrastim [Neupogen]) and, 3 weeks later, by a second high-dose course of cytarabine (ara-C, 1.5-2 g/m² q12h for 6 days) with peripheral blood progenitor cells and growthcourse, the first 10 patients (4 with mantle cell lymphoma) received two intravenous (IV) doses of rituximab at 375 mg/m2. The subsequently enrolled 10 consecutive patients (3 with mantle cell NHL) served as controls.

Peripheral blood progenitor cells were obtained by leukapheresis when the CD34+ cell count reached ³ 50/µL. The intention was to collect, after cyclophosphamide, a PCR-negative leukapheresis product containing a minimum of 11 × 10⁶/kg CD34+ cells. In the case of PCR-positive products, additional leukaphereses were performed after cytarabine. If the product was still PCR-positive, ex vivo immunologic purging with an anti-CD19 monoclonal antibody was performed, using a Miltenyi SuperMACS device. The results are summarized as follows:

CONCLUSION: We showed that rituximab, in combination with one or two courses of an effective high-dose antilymphoma therapy (in fact, this strategy was able to produce clinical remissions in 9 out of 10 such cases), allowed the harvesting of large amounts of tumor-free progenitor cells in all evaluable patients, including the 4 patients with mantle cell lymphoma. This in vivo purging strategy compares very favorably with ex vivo purging in terms of feasibility, costs, and overall success rate in harvesting an amount of uncontaminated CD34+ cells (ie, ³ 11× 10⁶/kg) fully adequate to support more than one cycle of subsequent myeloablative chemotherapy.

Click here for Dr. Bruce Cheson’s commentary on this abstract.