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

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 pre-treated patients this treatment also showed promising results, although the risk of severe infections needs to be considered.

Central nervous system relapse in a patient with mantle cell lymphoma in continuous clinical and molecular remission at six years since autografting.

Although molecular remissions have been frequently observed and associated with low likelihood of relapse in some lymphoid tumours, they are seldom reported in mantle cell lymphoma (MCL). We performed PCR analysis of a MCL patient with central nervous system (CNS) relapse occurring 76 months after autologous transplantation. Molecular follow-up showed constant absence of PCR-detectable disease, even after the onset of relapse. These data indicate that isolated CNS relapse may occur even after several years of continuous remission and cannot be excluded based on a persistent pattern of molecular remission. However, the prolonged remission duration observed in this patient suggests that achieving PCR-negativity may also be of benefit for MCL patients.

A validated real-time quantitative PCR approach shows a correlation between tumor burden and successful ex vivo purging in follicular lymphoma patients.

OBJECTIVE: Purging procedures are increasingly used to provide stem cell collections devoid of contaminating tumor cells. In follicle center lymphoma (FCL), most approaches eradicate polymerase chain reaction (PCR);-detectable disease in only a fraction of harvests undergoing ex vivo manipulation. In this study we evaluated whether there is a relationship between tumor burden of stem cell harvests and successful clearance of PCR-detectable disease following ex vivo manipulation. MATERIALS AND METHODS: To address this issue, we developed a real-time PCR approach for quantitative measurement of tumor contamination using the bcl-2 rearrangement. Real-time PCR was used to evaluate the relationship between tumor burden of stem-cell harvests and purging effectiveness in PCR(+) samples derived from 10 FCL patients. Ex vivo purging was performed using the MaxSep cell separator (Baxter Immunotherapy, Deerfield, IL, USA). RESULTS: Our real-time PCR method proved effective, sensitive, accurate, and reproducible. Four collections were successfully cleared of minimal residual disease (MRD) whereas six remained PCR(+). Real-time PCR showed that the four collections successfully cleared of MRD had a prepurging tumor burden significantly lower than those remaining PCR(+) (p = 0.04). CONCLUSION: This study provides the first evidence that evaluation of tumor burden in stem-cell harvests by real-time PCR can predict the effectiveness of therapeutic intervention in non-Hodgkin's lymphoma. Based on these findings, we foresee a more widespread use of this technique to evaluate the impact of different therapeutic approaches in FCL.