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Blood, 1 May 2005, Vol. 105, No. 9, pp. 3428-3433.
Prepublished online as a Blood First Edition Paper on January 6, 2005; DOI 10.1182/blood-2004-06-2490.


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Submitted June 30, 2004
Accepted December 24, 2004

Quantitative PCR of bone marrow BCL2/IgH positive cells at diagnosis predicts treatment response and long-term outcome in Follicular non Hodgkin's Lymphoma

Alessandro Rambaldi*, Emanuela Carlotti, Elena Oldani, Irene Della Starza, Michele Baccarani, Sergio Cortelazzo, Francesco Lauria, Luca Arcaini, Enrica Morra, Alessandro Pulsoni, Luigi Rigacci, Maurizio Rupolo, Francesco Zaja, Pier L Zinzani, Tiziano Barbui, and Robert Foa

Divisione di Ematologia, Ospedali Riuniti, Bergamo, Italy
Divisione di Ematologia, Dipartimento di Biotecnologie Cellulari ed Ematologia, Universita 'La Sapienza', Roma, Italy
Istituto di Ematologia e Oncologia Medica Seragnoli, Universita di Bologna, Bologna, Italy
Cattedra di Ematologia, Universita di Siena, Siena, Italy
Divisione di Ematologia IRCCS, Policlinico San Matteo, Universita di Pavia, Pavia, Italy
Divisione di Ematologia, Ospedale Niguarda, Milano, Italy
Cattedra di Ematologia, Universita di Firenze, Firenze, Italy
Dipartimento di Oncologia Medica, Centro di Riferimento Oncologico, IRCCS, Aviano, Italy
Cattedra di Ematologia, Universita di Udine, Udine, Italy

* Corresponding author; email: arambaldi{at}ospedaliriuniti.bergamo.it.

By real time quantitative PCR reaction (RQ-PCR) we evaluated BCL2/IgH+ cells in the bone marrow (BM) and peripheral blood (PB) of 86 follicular lymphoma patients treated with the sequential administration of CHOP 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% or 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 of patients with a low/intermediate or high tumor infiltration in the BM was 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< 0.006). RQ-PCR performed at presentation on BM samples predicts treatment response and long-term clinical outcome in follicular lymphoma patients


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