High-dose therapy (HDT) with peripheral blood stem cell transplantation is a treatment option for patients with advanced follicular, marginal, and mantle cell lymphoma. In this setting, frequent contamination of peripheral blood stem cell harvests by tumor cells may contribute to relapse.
The anti-CD20 monoclonal antibody rituximab (Rituxan) induces clinical response in such lymphomas (J Clin Oncol 16:2825, 1998; 18:317, 2000) and is efficient in removing circulating B cells from the peripheral blood. We therefore hypothesized that rituximab may be a useful in vivo purging agent prior to transplant therapy.
From May 1998 to May 2000, 12 patients with relapsed follicular (n = 9), transformed marginal zone (n = 2), and mantle cell (n = 1) lymphomas with bone marrow involvement and polymerase chain reaction (PCR)-detectable molecular markers were each treated with four courses of 375 mg/m2 of rituximab. At the time of treatment, the patients with follicular lymphoma had received no prior chemotherapy for their relapse and the other three patients were considered in first partial response (PR) after an anthracycline-containing regimen. All the patients were in PR after rituximab.
With a median delay of 2 months after the last infusion of rituximab, a mobilization regimen was delivered, consisting of cyclophosphamide (Cytoxan, Neosar) at 4.5 g/m2 and etoposide at 450 mg/m2 on day 1 with granulocyte colony-stimulating factor (G-CSF [Neupogen]) (5 µg/kg) from day 5 until the end of leukapheresis. All patients were collected with a median number of 5.5 × 106 CD34 cells/kg harvested (3-21) and 1 leukapheresis (1-3). As of February 2001, all the patients completed HDT with cyclophosphamide (60 mg/kg day 6 and day 5), etoposide (300 mg/m2 day 6 to day 4), and a single-dose total-body irradiation at day 1 (8 Gy).
In all patients, PCR analysis was performed in peripheral blood before rituximab and in the leukapheresis product with bcl-2-JH (n = 8), bcl-1-JH (n = 1), or CDR II/III-specific primers (n = 3). At the present time, follow-up PCR in peripheral blood is available in 8 patients. The proportion of harvests free of lymphoma cells is 9 out of 12 (75%). Engraftment to an absolute neutrophil count of 500 occurred at a median of 14 days, similar to historical data for non-Hodgkin’s lymphoma patients not receiving pretransplant rituximab. With a median follow-up of 4 months, all the patients are alive, with 10 in clinical complete remission (PCR leukapheresis product/PCR follow-up: -/- 8, +/- 1, +/+ 1) and 2 with progressive disease (-/+).
CONCLUSION: The combination of rituximab and HDT is effective for eliminating clinical tumor burden and minimal residual disease. A longer follow-up will be necessary to determine the molecular and clinical outcome of these patients.