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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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CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Quantitative PCR of bone marrow BCL2/IgH+ cells at diagnosis predicts treatment response and long-term outcome in follicular non-Hodgkin 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 Luigi Zinzani,
Tiziano Barbui, and
Robert Foa
From the From the Divisione di Ematologia, Ospedali Riuniti Bergamo, Bergamo, Italy; Divisione di Ematologia, Dipartimento di Biotecnologie Cellulari ed Ematologia, Università La Sapienza, Roma, Italy; Istituto di Ematologia e Oncologia Medica Seragnoli, Università di Bologna, Bologna, Italy; Cattedra di Ematologia, Università di Siena, Siena, Italy; Divisione di Ematologia IRCCS, Policlinico San Matteo, Università di Pavia, Pavia, Italy; Divisione di Ematologia, Ospedale Niguarda, Milano, Italy; Cattedra di Ematologia, Università di Firenze, Firenze, Italy; Oncologia Medica B e Nucleo di Ricerca Clinica e Laboratoristica in Ematologia, Dipartimento di Oncologia Medica, Centro di Riferimento Oncologico IRCCS, Aviano, Aviano, Italy; and Cattedra di Ematologia, Università di Udine, Italy.
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.
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