Monitoring of minimal residual disease after CHOP and rituximab in previously untreated patients with follicular lymphoma.
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).
Rambaldi
Alessandro
A
Divisione di Ematologia, Ospedali Riuniti Bergamo, Largo Barozzi 1, 24100 Bergamo, Italy. arambaldfi@ospedaliriuniti.bergamo.it
Lazzari
Manuela
M
Manzoni
Cristina
C
Carlotti
Emanuela
E
Arcaini
Luca
L
Baccarani
Michele
M
Barbui
Tiziano
T
Bernasconi
Carlo
C
Dastoli
Giuseppe
G
Fuga
Giovanna
G
Gamba
Enrica
E
Gargantini
Livio
L
Gattei
Valter
V
Lauria
Francesco
F
Lazzarino
Mario
M
Mandelli
Franco
F
Morra
Enrica
E
Pulsoni
Alessandro
A
Ribersani
Michela
M
Rossi-Ferrini
Pier Luigi
PL
Rupolo
Maurizio
M
Tura
Sante
S
Zagonel
Vittorina
V
Zaja
Francesco
F
Zinzani
PierLuigi
P
Reato
Gigliola
G
Foa
Robin
R
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000633:toxicity; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001773:Blood Cells; D001853:Bone Marrow; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005803:Genes, Immunoglobulin; D019254:Genes, bcl-2; D006801:Humans; D008224:Lymphoma, Follicular / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000188:drug therapy; D016133:Polymerase Chain Reaction; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D000069283:Rituximab; D016019:Survival Analysis; D014750:Vincristine / Q000008:administration & dosage
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone