Prior Rituximab (RTX) Administration Might Adversely Affect Stem Cell Harvest in Patients with Aggressive B-Cell Lymphomas.

Abstract

Rituximab-based regimens for in vivo purging or post-transplantation consolidation are increasingly incorporated in the autologous hemopoietic stem cell transplantation (AHCT) setting for B-cell lymphomas. However, prior RTX therapy has been associated with poor stem cell mobilization (SCM) and moreover, rituximab-related neutropenia has been described more frequently post-AHCT. We retrospectively studied 40 patients (pts) with B-cell aggressive NHL who underwent SCM between April 1995 and May 2004 and we analyzed the data related to stem cell harvest and the engraftment kinetics of the transplanted stem cells. Fifteen pts [median age: 48 (15–67) years] were treated with 2 (1–6) doses of RTX at 375mg/m2(RTX group), 50 (7–180) days prior to SCM. They had received 2 (1–4) lines of chemotherapy (ChT); 4 pts had also received radiotherapy. At the time of SCM, 7 pts had refractory disease (REFD), 5 pts were in relapse (REL) and 2 were in second complete remission (CR2). Twenty-five pts [median age 35 (13–57) years] received only ChT prior to SCM (Non-RTX group). They had been treated with 2 (1–5) ChT lines (5 pts plus irradiation), 75 (18–3,361) days before SCM; pts' disease status was: REFD: 9 pts, REL: 11 pts, CR1: 2 and CR2: 3 pts. Fludarabine-based regimens were not used. The majority (37/40 patients) received mobilization ChT with DICE (Dexamethasone 40mg x 5 days, Ifosphamide 1000mg/m2 x 5 days, Cisplatyl 25mg/m2 x 5 days, Etoposide 100mg/m2 x 5 days); The remaining three patients were treated with DHAP, Cyclophosphamide and G-CSF-only. Leukaphereses were performed until a target cell dose of >2 x 106/kg CD34+cells was harvested. 4/15 and 5/25 patients of the RTX and non-RTX group respectively, received an additional 6μg/kg G-CSF because the above threshold was not reached during the first two courses. The median time of harvest completion was similar for the two groups (3 days). The median CD34+ cell dose collected (3.1 vs 5.17 x 106 cells/kg, p:0.04) and the median CD34+ yield per day (0.93 vs 2.59 x 106 cells/kg, p:0.04) was lower in the RTX group. The median mononuclear cell dose was slightly higher in the RTX group (6.2 vs 5.77 x 108 cells/kg, NS). There was only one mobilization failure in the RTX group and remobilization was not attempted due to disease progression. In the non-RTX group, a sufficient stem cell number was collected in 22/25 pts after the 1st attempt whereas 3 pts required a 2nd SCM (2 pts) or additional bone marrow harvest (1pt). Patients demonstrating chemosensitive disease after treatment underwent transplantation with BEAM as conditioning (8/15 of the RTX group and 22/25 of the non-RTX group). All patients engrafted satisfactorily. Median time to neutrophils > 500/mm3 was prolonged in the RTX group (11 vs 10 days, NS). Median time to platelets > 20,000/mm3 was similar for the 2 groups (13 days). RTX group required more RBC units during AHCT (median 9 vs 7, NS); median time for platelet transfusion independence was shorter (7 vs 8 days, NS). In a multivariate analysis, RTX was the only variable among those studied (age, disease status, lines of previous ChT, and RTX administration) which was significantly associated with the total and per day CD34+ cell dose collected. This study suggests that prior RTX treatment might adversely affect stem cell collection in this cohort of pts; the possible mechanisms of this effect are unclear.