Quantitative PCR of bone marrow BCL2/IgH+ cells at diagnosis predicts treatment response and long-term outcome in follicular non-Hodgkin lymphoma.
By real-time quantitative polymerase chain reaction (RQ-PCR), we evaluated BCL2/IgH(+) cells in the bone marrow (BM) and peripheral blood (PB) from 86 patients with follicular lymphoma treated with the sequential administration of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) and rituximab. At diagnosis, the amount of BCL2/IgH(+) cells in the BM was low (1 BCL2/IgH(+) cell in 1000-100 000 normal cells) in 43% of patients, intermediate (1 in 100-1000) in 34%, and high (> 1 in 100) in 23%. A 2 log decrease of BCL2/IgH(+) cells was achieved after CHOP and an additional 2 log reduction following rituximab. By multivariate analysis, a low level of BCL2/IgH(+) cells in the BM at diagnosis was the best predictor for the achievement of a complete clinical and molecular response. At 5 years, the event-free survival rates of patients with a low/intermediate or high tumor infiltration in the BM were 59% and 32%, respectively. The freedom from recurrence of patients who achieved a molecular response in the BM, no matter whether after CHOP alone or CHOP and rituximab, was 64% as compared to 32% for patients who did not (P < .006). RQ-PCR performed at presentation on BM samples predicts treatment response and long-term clinical outcome in patients with follicular lymphoma.
Rambaldi
Alessandro
A
Divisione di Ematologia, Ospedali Riuniti Largo Barozzi 1, 24100, Bergamo, Italy. arambaldi@ospedaliriuniti.bergamo.it
Carlotti
Emanuela
E
Oldani
Elena
E
Della Starza
Irene
I
Baccarani
Michele
M
Cortelazzo
Sergio
S
Lauria
Francesco
F
Arcaini
Luca
L
Morra
Enrica
E
Pulsoni
Alessandro
A
Rigacci
Luigi
L
Rupolo
Maurizio
M
Zaja
Francesco
F
Zinzani
Pier Luigi
PL
Barbui
Tiziano
T
Foa
Robert
R
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001854:Bone Marrow Cells / Q000473:pathology*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000032:analysis*; D008224:Lymphoma, Follicular / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011239:Prednisolone / Q000008:administration & dosage; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D000069283:Rituximab; D016019:Survival Analysis; D014750:Vincristine / Q000008:administration & dosage
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007143:Immunoglobulin Heavy Chains; D019253:Proto-Oncogene Proteins c-bcl-2; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone