Effect of High-Dose Rituximab on Peripheral Blood Stem Cell Mobilization in Intermediate Grade Non-Hodgkin's Lymphomas.

Abstract

High dose chemotherapy followed by autologous stem cell transplantation (ASCT) is considered to be standard therapy for patients with intermediate grade NHL (IGNHL) in chemosensitive relapse. In recent years rituximab has been widely used for in vivo purging of lymphoma cells from apheresis products, however its impact on kinetics of stem cell mobilization and engraftment are not well characterized. We studied 69 patients with IGNHL who were mobilized using rituximab plus chemotherapy or with chemotherapy alone. 31 patients (No-R group) were mobilized with ifosfamide (10 g/m2), and etoposide (150 mg/m2 every 12 hours for 6 doses) followed by G-CSF (12 mcg/kg/day). 38 patients (R group) also received 2 doses of rituximab (375 mg/m2 and 1000 mg/m2) on days 1 and 10. Patients underwent HDT following successful stem cell collection. HDT was standard BEAM (+ rituximab for patients in the R group) regimen in most patients. 15 patients received a cycle of CVP (cyclophosphamide, cisplatin, etoposide) prior to BEAM because of failure to achieve at least a PR following mobilization chemotherapy (all in the No-R arm).RESULTS: The baseline characteristics of the 2 groups are summarized in Table 1. Patients in the No-R group were more likely to have stage III/IV disease, and were more likely to have BM involvement with lymphoma, but had received fewer number of chemotherapy regimens received prior to mobilization. Failure to mobilize was defined as failure to reach a circulating CD34 count of 10/mcl. The target cell dose was a minimum of 4 x 106 CD34+ cells/kg. The apheresis data is summarized in Table 2. All 31 patients in the No-R group mobilized the target cell dose (NA-1). In the R group 7.9% did not reach the target cell dose (P=NS). Median time to neutrophil engraftment after ASCT was 10 (8–17) and 11 (9–37) days in the No-R and R groups respectively (P=0.01). The OS and DFS at 2 years were 45% (27–61) and 39% (22–55) and 78% (51–92) and 63% (38–51) respectively in the No-R and R group (P=0.001 and 0.01).CONCLUSION: High dose rituximab added to the mobilization regimen does not affect the ability to collect adequate number of stem cells for ASCT. Incidence of bacteremic episodes was higher in the rituximab group. The OS and DFS were significantly longer in patients receiving rituximab.Table 2. Apheresis DataRituximab group (N=38)No rituximab group (N=31)P=valueMedian days of apheresis (range)2 (1–5)2 (1–7)NSFailure to mobilize10NSFailure to collect 4 x 106CD34+cells/kg30NSMedian CD 34+cells/kg (range)6.5 (0–31.15) x 10613.7 (4.8–148) x 106<.0001PRBC transfusions median (range)1 (0–5)0 (0–8).01Platelet transfusions median (range)2 (0–6)1 (1–3).008No. of patients with infections1380.45Infectious episodes26 (22 bacterial)11 (6 bacterial)0.01Time to ANC > 500/mm3 after mobilization median (range)13 (11–18)14 (6–24) NA 30.7Table 1: Baseline characteristicsRituximab groupNo rituximab groupP valueN=38N=31Age years (range)49.9 (19–70 )48 (26–590.68Stage III/IV (%)9 (23.7%)13 (43.3%).003No. of prior chemoregimens (median, range)2 (1–5)1 (1–3).001IPI score (median, range)0 (0–2)1 (0–2) NA 5.03LDH ≥ normal (%)8 (21%)8 (30.7%)0.78BM involvement (%)0 (0)8 (25.8)