In Vivo Purging With Rituximab During Stem Cell Transplantation for Indolent Lymphoma

Autologous peripheral blood stem-cell (PBSC) transplantation may play an important role in the treatment of indolent lymphomas, as well as aggressive lymphomas. Concern about the contamination of the autologous graft with lymphoma remains, as contamination may shorten disease-free survival.

Rituximab (Rituxan) used during stem cell mobilization is a promising method for purging PBSCs of lymphoma in vivo. Similarly, when administered following transplantation, this antibody may serve as adjuvant immunotherapy. We are conducting trials with rituximab during PBSC transplant for non-Hodgkin’s lymphoma. (NHL). The purpose of these trials is to evaluate the safety and efficacy of in vivo purging with rituximab. Tumor contamination of the PBSC graft is being measured with lymphoma colony formation and/or polymerase chain reaction (PCR).

A total of 51 patients (32 males, 19 females) at a median age of 52 years (range, 32 to 67 years) have been accrued. Diagnoses included: follicular (23 patients), mantle cell (10 patients), small lymphocytic/chronic lymphocytic (13 patients), marginal zone (3 patients), and lymphoplasmacytic lymphomas (2 patients).

Patients received 375 mg/m² of rituximab on day 1 of mobilization, followed by cyclophosphamide (Cytoxan, Neosar), 2.5 g/m² on day 4, and either granulocyte-colony-stimulating factor (G-CSF [Neupogen]), 10 µg/kg starting on day 5, or granulocyte-macrophage colony-stimulating factor (GM-CSF [Leukine, Prokine]), 10 µg/kg on days 5 to 11, and G-CSF ,10 mg/kg starting on day 10 through the last day of apheresis, depending on the protocol.

Stem cells were collected using a high-volume apheresis procedure. The last 26 patients were CD34-selected for tumor depletion if ³ 5× 10⁶ CD34/kg were collected. The preparative regimen consisted of either cyclophosphamide and total-body irradiation or busulfan (Myleran) and cyclophosphamide in patients who had received prior external irradiation. Following transplantation, patients received one or four doses of rituximab, depending on the protocol.In 46 of the 51 patients, stem cells were successfully mobilized (median, 10.9 × 10⁶ CD34/kg; range, 2.24 × 106 to 59.5 × 10⁶ CD34/ kg). Of the 46 patients, 38 required only one high-volume apheresis.

A total of 19 grafts were CD34 selected. Of the 19 grafts, 17 were lymphoma free in a clonogenic assay performed prior to CD34 selection, and 17 were lymphoma free following selection. Seven recipients of unmanipulated grafts had lymphomas that were positive for t(11;14) or t(14;18), and only one of these grafts was PCR positive. Results of PCR analysis of CD34-selected grafts are pending.Although follow-up is short, there has been little additional toxicity and only 1 death in the 35 transplanted patients.

CONCLUSION: Although these results are preliminary, it appears that rituximab may be an effective method for in vivo purging autologous grafts of indolent lymphoma.

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