Monitoring of minimal residual disease after CHOP and rituximab in previously untreated patients with follicular lymphoma

Rambaldi, Alessandro; Lazzari, Manuela; Manzoni, Cristina; Carlotti, Emanuela; Arcaini, Luca; Baccarani, Michele; Barbui, Tiziano; Bernasconi, Carlo; Dastoli, Giuseppe; Fuga, G C; Gamba, Enrica; Gargantini, Livio; Gattei, Valter; Lauria, F.; Lazzarino, Mario; Mandelli, Franco; Morra, Enrica; Pulsoni, Alessandro; Ribersani, Michela; Rossi-Ferrini, P; Rupolo, Maurizio; Tura, S; Zagonel, Vittorina; Zaja, Francesco; Zinzani, Pier Luigi; Reato, Gigliola; Foà, Robin

doi:10.1182/blood.v99.3.856

Cited by 154 publications

(113 citation statements)

References 44 publications

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“…It could be demonstrated that high-dose therapy [3] as well as conventionally dosed treatment [4,5] was able to achieve complete molecular responses in a significant number of patients. In these as well as in other reports [6][7][8][9], MRD negativity after treatment correlates with prolonged overall and progression-free survival. Usually, semi-nested or nested PCR approaches have been used to detect t(14;18) [1].…”

Section: Introductionsupporting

confidence: 83%

“…If it would be possible to predict disease control after first-line therapy, these therapies could be selected for patients with a high likelihood of early relapse. With qualitative PCR, several studies were able to document a relationship between molecular response and time to relapse in patients treated with standard-dose chemotherapy [4,5,26], with high-dose chemotherapy [7,[27][28][29][30] and with rituximab-containing regimen [8,31,32]. Due to the low number of patients and the limited follow-up time of 6 months, we can only speculate on the role of molecular diagnostics for the prediction of relapsed disease.…”

Section: Discussionmentioning

confidence: 99%

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Commercial LightCycler®-based quantitative real-time PCR compared to nested PCR for monitoring of Bcl-2/IgH rearrangement in patients with follicular lymphoma

Kornacker

Schmitt

et al. 2008

Ann Hematol

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Section: Introductionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Commercial LightCycler®-based quantitative real-time PCR compared to nested PCR for monitoring of Bcl-2/IgH rearrangement in patients with follicular lymphoma

Kornacker

Schmitt

et al. 2008

Ann Hematol

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“…9 Moreover, the association of Rituximab and CHOP was advantageous even from the molecular point of view, with 70% of molecular remissions. 10 If the role of HD therapy and autologous transplantation appears to be promising in indolent NHL, 11 the clinical relevance of the presence of contaminating tumor cells in harvests and detectable minimal residual disease is still a matter for debate.…”

Section: Discussionmentioning

confidence: 99%

Quantitative molecular evaluation in autotransplant programs for follicular lymphoma: efficacy of in vivo purging by Rituximab

Galimberti

Guerrini

Morabito

et al. 2003

Bone Marrow Transplant

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Summary:The main aim of this paper was to compare results of Genescan and real-time PCR methods in order to detect contamination in harvests from patients with follicular lymphoma. The secondary goal was to evaluate the efficacy of Rituximab as an in vivo purging agent. A total of 23 patients had been treated with CHOP followed by either high-dose therapy (12 patients) or high-dose plus Rituximab (11 patients), both followed by autologous transplantation. Results show that 86% of harvests from patients treated whith Rituximab were PCR-negative compared to 14.3% from controls. Real-time PCR was more sensitive than Genescan PCR; quantitative analysis revealed a correlation between the amount of contamination in the harvests and relapse after transplantation. Whereas all patients reinfused with negative aphereses achieved complete remission and showed a significantly better 5-year PFS (100%) compared to those reinfused with contaminated samples (41%), a very low amount of contamination does not appear to negatively affect outcome, suggesting that determination of a cutoff in the contamination level of harvests could be useful. Results suggest that real-time PCR is superior to Genescan PCR to select transplantable harvests and confirm the ability of Rituximab as an in vivo purging tool for follicular lymphoma. Bone Marrow Transplantation (2003) 32, 57-63. doi:10.1038/sj.bmt.1704102 Keywords: minimal residual disease; follicular lymphoma; autologous transplantation; rituximab; purging Although indolent non-Hodgkin's lymphoma (NHL) patients have a fairly long survival, they frequently experience relapses and truly curative treatments are not available to date. The most efficacious recent protocols involve high-dose therapy and anti-CD20 monoclonal antibody (Rituximab). 1 This provides some advantages, at least in terms of halting disease progression. 2 Owing to the long median survival of patients with indolent diseases, definitive clinical results of new trials may not become evident for a long period of time. Consequently, surrogate end points of survival, such as clearance of neoplastic cells from bone marrow or peripheral blood, could be provisionally considered. In the great majority of follicular lymphoma patients, the neoplastic clone is characterized by a reciprocal balanced chromosomal translocation, the t(14;18) (q32;q21), involving the bcl2 gene on chromosome 18 and the immunoglobulin heavy chain gene on chromosome 14. 3 Highly sensitive molecular methods for detecting the t(14;18) have been developed in an attempt to clarify the possible clinical role of minimal residual disease. After a program of high-dose therapy and autotransplantation, up to 68% of patients provided uncontaminated harvests. Indeed, those patients receiving PCR-negative stem cells maintained both negative molecular status and continuous clinical remission. 4 Nevertheless, these data derive from a labor-intensive and time-consuming molecular method consisting of conventional PCR assays followed by hybridization with patient-specific rad...

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“…An increase in molecular remission was observed after rituximab consolidation in both chemotherapy groups, from 20 to 40% in the CHOP group and from 34 to 59% in the FM group. Sequential therapy with short-course chemotherapy followed by rituximab has also been investigated in previously untreated patients (Rambaldi et al, 2002), and the results are similar to those for concurrent therapy. The combination of rituximab plus CVP (chlorambucil, vincristine, prednisone) vs CVP alone as first-line therapy for indolent NHL is currently being studied in a phase III randomised trial (M39021 Trial).…”

Section: Previously Untreated Indolent Nhlmentioning

confidence: 84%

Clinical use of rituximab in haematological malignancies

2003

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Rituximab is a chimeric human/mouse monoclonal antibody that is approved for the treatment of relapsed and refractory nonHodgkin's lymphoma (NHL) and in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy as first-line therapy for diffuse large B-cell NHL, where it has shown the first survival advantage over CHOP alone in more than 20 years. Strategies to help define the optimal therapeutic usage of rituximab are being assessed, including first-line and maintenance or extended therapy, and the combination of rituximab with chemotherapy in indolent NHL. Emerging data suggest that earlier use may yield higher response rates, extended therapy can prolong remission, and the addition of rituximab to chemotherapy can increase clinical and molecular remission rates when compared with those achieved using chemotherapy alone. Studies in the peritransplant setting suggest a role for rituximab in vivo purging prior to transplant and/or maintenance rituximab as a means of clearing minimal residual disease. Rituximab has also shown activity in other B-cell disorders such as chronic lymphocytic leukaemia. The full potential of this immunotherapeutic agent remains to be defined in ongoing and future clinical trials.

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Monitoring of minimal residual disease after CHOP and rituximab in previously untreated patients with follicular lymphoma

Cited by 154 publications

References 44 publications

Commercial LightCycler®-based quantitative real-time PCR compared to nested PCR for monitoring of Bcl-2/IgH rearrangement in patients with follicular lymphoma

Commercial LightCycler®-based quantitative real-time PCR compared to nested PCR for monitoring of Bcl-2/IgH rearrangement in patients with follicular lymphoma

Quantitative molecular evaluation in autotransplant programs for follicular lymphoma: efficacy of in vivo purging by Rituximab

Clinical use of rituximab in haematological malignancies

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