Abstract

Introduction: Rituximab is a monoclonal antibody commonly used in B-DLCL both in salvage regimens and in combination with first-line chemotherapy. Some studies have reported delays in neutrophil or platelet engraftment after ASCT in patients treated with high dose chemotherapy and Rituximab prior to ASCT. We investigated the effect of adding Rituximab prior to ASCT on peripheral blood stem cell (PBSC) harvest, time to engraftment and short-term toxicity post ASCT.

Patients and methods: We analyze stem cell mobilization, engraftment (median time to absolute neutrophil count > 500/mm3 for three consecutive days and platelets > 50.000) and short-term toxicity after ASCT (< 30 days) in two groups of patients affected by B-DLCL at diagnosis enrolled into two consecutive trials with or without Rituximab in combination with chemotherapy. All patients were < 61 years with B-DLCL at age-adjusted IPI Intermediate-High (IH) or High (H) risk and/or with bone marrow (BM) involvement.

Group A: an intensified chemoimmunotherapy regimen R-MegaCEOP (Rituximab 375 mg/m2 day 1, CTX 1200 mg/m2 + EPI 110 mg/m2 + VCR 1.4 mg/m2 day 3 and PDN 40 mg/m2 days 3 to 7) every 14 days with G-CSF support for 4 courses; patients in complete response (CR) or partial response (PR) received two courses of intensified chemotherapy R-MAD (Mitoxantrone 8 mg/m2 + ARA-C 2000 mg/m2/12h + Dexamethasone 4 mg/m2/12h days 1 to 3 and Rituximab 375 mg/m2 day 4 and before PBSC harvest).

Group B: MACOP-B 8 weeks + 2 courses of MAD (in patients in CR or PR) without Rituximab. Both groups were given ASCT with BEAM as conditioning regimen. Clinical characteristics at diagnosis were well balanced between the two groups.

Results: 68 patients are evaluable: 35 pts in group A (with Rituximab) and 33 pts in group B (without Rituximab). All patients in both groups collected more than 2 x 106 CD34+ cell/kg. Median CD34+ cell/kg in group A was 13 x 106 (range 0-37) compared with 41 x 106 in group B (range 0–253) with no statistically significant difference. Median time to neutrophils engraftment after ASCT was similar in the two groups: 9 days in group A and 10 days in group B. No delay in the platelet recovery was observed in patients treated with chemoimmunotherapy: 15 days in group A vs 16 days in group B. Few severe early toxicities (WHO grade 3–4) were reported with no differences between group A vs B: severe mucositis in 11 pts vs 23 pts, gastrointestinal in 6 pts vs 4 pts. Severe infections occurred in 10 patients: group A 6 patients (2 Gram+ sepsis, 1 Gram- sepsis, 1 FUO, 2 bacterial pneumonia); group B 4 patients (2 FUO, 1 bacterial and 1 viral pneumonia). One patient in group A died of bacterial pneumonia after ASCT.

Conclusions: Treatment with Rituximab may be safely included in a pre-ASCT high dose chemotherapy regimen with no delay in stem cell harvest, engraftment and without increased early toxicity after ASCT.

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