Concurrent administration of high-dose chemotherapy and rituximab is a feasible and effective chemo/immunotherapy for patients with high-risk non-Hodgkin's lymphoma

Abstract

The aim of this study was to investigate feasibility, tolerability and efficacy of rituximab-supplemented high-dose sequential chemotherapy (R-HDS) with peripheral blood progenitor cell autografting as frontline or salvage treatment in patients with advanced non-Hodgkin's lymphoma (NHL). Thirty-two patients have been treated: 14 at disease onset and 18 with relapsed or progressive disease. R-HDS regimens included six courses of rituximab. Rituximab was delivered either concurrently with high-dose chemotherapy to exploit the in vivo purging properties of the drug as well as at the end of the treatment plan to target minimal residual disease. All patients treated at disease onset completed their treatment with no life-threatening toxicity, while two toxic deaths due to severe bilateral pneumonia were observed among patients treated due to relapsed or refractory disease. Thirteen of 14 patients treated up-front achieved CR. Among pre-treated patients 10 of 18 achieved CR with better results in patients with relapsed (seven of eight) compared to progressive disease (three of 10). PCR analysis was carried out in indolent lymphoma patients: nine of nine follicular lymphomas and three of six CD5-positive NHL collected PCR-negative peripheral blood progenitor cell harvests. The results of this pilot study show that R-HDS is feasible and effective with acceptable toxicity when used at disease onset. In pretreated patients this treatment also showed promising results, although the risk of severe infections needs to be considered. Leukemia (2001Leukemia ( ) 15, 1941Leukemia ( -1949

Prolonged survival in poor-risk diffuse large B-cell lymphoma following front-line treatment with rituximab-supplemented, early-intensified chemotherapy with multiple autologous hematopoietic stem cell support: a multicenter study by GITIL (Gruppo Italiano Terapie Innovative nei Linfomi)

“…7,8 Furthermore, although rituximab efficacy has chiefly been proved in combination with conventional chemotherapy, it may also improve autograftbased programs, particularly as an in vivo purging agent before peripheral blood progenitor cell (PBPC) harvests. [9][10][11][12][13] Thus, rituximab-supplemented intensive programs with autograft might represent an effective alternative to R-CHOP in DLB-CL patients with unfavorable clinical presentation.…”

Prolonged survival and low incidence of late toxic sequelae in advanced follicular lymphoma treated with a TBI-free autografting program: updated results of the multicenter consecutive GITMO trial

“…Previous observations have shown that HDS can easily be combined with Rituximab with the additive effect of powerful Rituximab-mediated in vivo purging. 55,56 Thus, Rituximab-supplemented HDS appears to be an attractive option in studies aiming to verify whether doseintensification is still worthwhile in the monoclonal antibody era. Randomized trials are ongoing and will hopefully provide an answer to this important matter (Ladetto et al, Blood 2005; 106 abstract 675).…”

Marked telomere shortening in mobilized peripheral blood progenitor cells (PBPC) following two tightly spaced high-dose chemotherapy courses with G-CSF

“…34 In addition, the combination of Rituximab with repeated chemotherapy administrations had an in vivo purging effect, as demonstrated by the high frequency of PCR-negative harvests following hd-Ara-C observed in mantle-cell and relapsed follicular lymphoma patients. 44,45 Reduction of tumor contamination might explain the preferential use of PBPC collected after repeated chemotherapy courses.…”