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

Author

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

Subjects
Adult, Male, medicine.medical_specialty, Neoplasm, Residual, medicine.medical_treatment, Immunology, Follicular lymphoma, CHOP, Biochemistry, Gastroenterology, Polymerase Chain Reaction, Antibodies, Monoclonal, Murine-Derived, Bone Marrow, hemic and lymphatic diseases, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Cyclophosphamide, Lymphoma, Follicular, Survival analysis, Aged, Chemotherapy, Blood Cells, Genes, Immunoglobulin, business.industry, Antibodies, Monoclonal, Cell Biology, Hematology, Middle Aged, medicine.disease, Prognosis, Minimal residual disease, Survival Analysis, Surgery, Lymphoma, Genes, bcl-2, medicine.anatomical_structure, Doxorubicin, Vincristine, Prednisone, Rituximab, Female, Bone marrow, business, medicine.drug
Abstract

Minimal residual disease (MRD) following sequential administration of CHOP and rituximab was studied in previously untreated patients with follicular lymphoma. At diagnosis, the presence of Bcl-2/IgH-positive cells in the peripheral blood (PB) and/or bone marrow (BM) was demonstrated in all patients (n = 128) by polymerase chain reaction (PCR) analysis. Patients who achieved a clinical response following CHOP but remained PCR-positive were eligible for rituximab (375 mg/m2 intravenously, weekly for 4 weeks). After CHOP, 57% achieved a complete response (CR), 37% a partial response (PR), and 6% were nonresponders (NR). At this stage, patients proving PCR-negative (n = 41) or failing to achieve a clinical response (n = 8) were excluded from rituximab treatment. Seventy-seven patients received rituximab and entered a scheduled MRD follow-up program. At the first molecular follow-up (+12 weeks), 59% had converted to PCR negativity in the BM and PB, with a further increase documented at the second control (+28 weeks) with 74% PCR negative. At the last molecular follow-up (+44 weeks), 63% of the patients remained PCR negative. At 3 years, the estimated overall survival of all patients is 95% (95% confidence interval [CI], 86-98). For patients achieving PCR-negative status following CHOP and therefore excluded from rituximab treatment, freedom from recurrence (FFR) was 52% (95% CI, 28-71). For patients treated with rituximab, a durable PCR-negative status was associated with a better clinical outcome since FFR was 57% (95% CI, 23-81) compared with 20% (95% CI, 4-46) in patients who never achieved or lost the molecular negativity ( P

Published
2002

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

Author

Rambaldi A, Lazzari M, Manzoni C, Carlotti E, Arcaini L, Baccarani M, Barbui T, Bernasconi C, Dastoli G, Fuga G, Gamba E, Gargantini L, Gattei V, Lauria F, Lazzarino M, Mandelli F, Morra E, Pulsoni A, Ribersani M, Rossi-Ferrini PL, Rupolo M, Tura S, Zagonel V, Zaja F, Zinzani P, Reato G, and Foa R

Subjects
Adult, Aged, Antibodies, Monoclonal toxicity, Antibodies, Monoclonal, Murine-Derived, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Blood Cells, Bone Marrow, Cyclophosphamide administration & dosage, Doxorubicin administration & dosage, Female, Genes, Immunoglobulin, Genes, bcl-2, Humans, Lymphoma, Follicular diagnosis, Lymphoma, Follicular mortality, Male, Middle Aged, Neoplasm, Residual drug therapy, Polymerase Chain Reaction, Prednisone administration & dosage, Prognosis, Rituximab, Survival Analysis, Vincristine administration & dosage, Antibodies, Monoclonal administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Lymphoma, Follicular drug therapy, Neoplasm, Residual diagnosis
Abstract

Minimal residual disease (MRD) following sequential administration of CHOP and rituximab was studied in previously untreated patients with follicular lymphoma. At diagnosis, the presence of Bcl-2/IgH-positive cells in the peripheral blood (PB) and/or bone marrow (BM) was demonstrated in all patients (n = 128) by polymerase chain reaction (PCR) analysis. Patients who achieved a clinical response following CHOP but remained PCR-positive were eligible for rituximab (375 mg/m(2) intravenously, weekly for 4 weeks). After CHOP, 57% achieved a complete response (CR), 37% a partial response (PR), and 6% were nonresponders (NR). At this stage, patients proving PCR-negative (n = 41) or failing to achieve a clinical response (n = 8) were excluded from rituximab treatment. Seventy-seven patients received rituximab and entered a scheduled MRD follow-up program. At the first molecular follow-up (+12 weeks), 59% had converted to PCR negativity in the BM and PB, with a further increase documented at the second control (+28 weeks) with 74% PCR negative. At the last molecular follow-up (+44 weeks), 63% of the patients remained PCR negative. At 3 years, the estimated overall survival of all patients is 95% (95% confidence interval [CI], 86-98). For patients achieving PCR-negative status following CHOP and therefore excluded from rituximab treatment, freedom from recurrence (FFR) was 52% (95% CI, 28-71). For patients treated with rituximab, a durable PCR-negative status was associated with a better clinical outcome since FFR was 57% (95% CI, 23-81) compared with 20% (95% CI, 4-46) in patients who never achieved or lost the molecular negativity (P <.001).

Published
2002
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