In Vivo Purging With Rituximab Prior to Stem Cell Collection Is Associated With Persistent Molecular Evidence of t(14;18) That Often Disappears Post-Transplant in Patients With Follicular Lymphoma

We previously reported that “in vivo purging” with rituximab (Rituxan) during stem-cell collection is safe and does not adversely affect engraftment. We now report on our transplant experience with rituximab. From June 1998 to December 1999, we enrolled 16 patients and transplanted 14 patients with relapsed follicular lymphoma (FL) in a phase II study using rituximab as an in vivo purge and as two 4-week courses at months 2 and 6 following high-dose chemotherapy. Patients’ stem cells were mobilized with granulocyte colony-stimulating factor (G-CSF [Neupogen; 10µg/kg/d for 5 days) and rituximab (375 mg/kg as a single infusion) 2 days (N = 9) or 5 days (N = 6) prior to stem-cell harvesting via large-volume leukapheresis. Median age was 52 years and median International Prognostic Index (IPI) at first assessment was low. Patients were first assessed following a median best remission duration of 13.5 months to previous chemotherapy and prior chemotherapy exposure of 4 to 11 months (median, 6 months).

In all patients, stem cells were successfully collected in a median of 1 day, with a final graft of 3.45 × 10⁶ CD34-positive cells/kg (± 2.3 to 6.9 × 10⁶ CD34-positive cells/kg). These patients received a median of 3.5 cycles of salvage chemotherapy (DHAP [dexamethasone, ara-C, and Platinol], or CHOP [cyclophosphamide, doxorubicin HCl, Oncovin, and prednisone]) and were transplanted with CBV (cyclophosphamide, BCNU, and VePesid) conditioning a median of 165 days following the first assessment. Median time to neutrophil engraftment was 11 days (range, 9 to 12 days) and median time to platelet independence, 9 days (4 to 22 days). Patients received a median of 4 units of packed red blood cells (range, 2 to 11 units) and 3 platelet transfusions of 5 units each (1 to 13 transfusions). Of the 14 patients, 6 have nearly completed all nine infusions of rituximab.

There were three episodes of grade 4 neutropenia, one seen after the first infusion post-transplant and one following the seventh. All of the episodes resolved spontaneously, although one patient was hospitalized briefly with febrile neutropenia. One patient experienced persistent, grade 3, seronegative inflammatory arthritis immediately following neutrophil engraftment but has received the first course of rituximab uneventfully. One patient, who was successfully treated for pulmonary aspergillosis post-transplant, did not receive his second course of rituximab because of the late development of presumed hepatosplenic fungal infection. Two patients were treated for presumed BCNU-induced pulmonary pneumonitis; one patient had a V1 distribution herpes zoster infection, and two patients developed undiagnosable pulmonary nodules that have resolved spontaneously.

At a median follow-up of 202 days, eight patients were in partial response (PR) and six, in complete response (CR). Polymerase chain reaction (PCR)–detectable lymphoma (nested PCR sensitivity, 1 in 10⁵ cells) was demonstrated in the peripheral blood (PB) or bone marrow (BM) of seven patients pretransplant. Although the stem-cell products of 6of 7patients remained PCR positive, 5of 7patients have become PCR negative in PB and BM at 8 weeks post-transplant, and 7of 7 became PCR negative at 24 weeks and have remained persistently PCR negative up to 1 year post-transplant.

CONCLUSION: The use of rituximab as an in vivo purge and in the minimal disease state following autologous transplantation for FL is safe and feasible. Molecular remissions may be achieved with this approach, suggesting that in vivo purging with rituximab may be impairing the viability of lymphoma cells shown to contaminate the stem-cell graft. Further follow-up is required to assess the efficacy of this transplantation approach.

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