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Prepublished online as a Blood First Edition Paper on May 1, 2003; DOI 10.1182/blood-2002-12-3789.
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Blood, 1 September 2003, Vol. 102, No. 5, pp. 1588-1594
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC
TRIALS
Cyclin D1 overexpression is a favorable prognostic variable for newly diagnosed multiple myeloma patients treated with high-dose chemotherapy and single or double autologous transplantation
Simona Soverini,
Michele Cavo,
Claudia Cellini,
Carolina Terragna,
Elena Zamagni,
Deborah Ruggeri,
Nicoletta Testoni,
Patrizia Tosi,
Antonio de Vivo,
Marilina Amabile,
Tiziana Grafone,
Emanuela Ottaviani,
Barbara Giannini,
Delia Cangini,
Francesca Bonifazi,
Antonino Neri,
Sonia Fabris,
Sante Tura,
Michele Baccarani, and
Giovanni Martinelli
From the Istituto di Ematologia ed Oncologia Medica
"Seràgnoli," Università di Bologna, Italy; and the
Laboratorio di Ematologia Sperimentale e Genetica Molecolare, Servizio di
Ematologia, Ospedale Maggiore Istituto di Ricovero e Cura a Carattere
Scientifico (IRCCS), Milano, Italy.
We used a sensitive real-time reverse transcription–polymerase chain
reaction assay to quantify cyclin D1 mRNA levels in bone marrow
samples collected at diagnosis from 74 newly diagnosed multiple myeloma (MM)
patients who were randomized to undergo either single or double autologous
peripheral blood stem cell transplantation as part of first-line therapy for
their malignancy. In 46 cases, fluorescence in situ hybridization (FISH)
analysis and/or conventional cytogenetics were performed to detect chromosome
11 abnormalities. Patients with the t(11;14) or trisomy 11 significantly
overexpressed cyclin D1 (P < .0001) in comparison with
patients without 11q abnormalities, who had cyclin D1 mRNA levels
similar to healthy donors. Overall, 32 (43%) of 74 patients showed cyclin
D1 overexpression. No difference was found between cyclin
D1–positive (group A) and cyclin D1–negative (group
B) patients with respect to presenting clinical and laboratory
characteristics, including chromosome 13 abnormalities, as well as to response
to therapy and overall survival, both of which were calculated on an
intent-to-treat basis. Patients who overexpressed cyclin D1 had
significantly longer duration of remission in comparison with patients who did
not (41 vs 26 months, respectively; P = .02). As a result, median
event-free survival (EFS) was longer in group A than in group B (33 vs 24
months, respectively; P = .055). We concluded that cyclin D1
overexpression is closely associated with 11q abnormalities and identifies a
subset of MM patients who are more likely to have prolonged duration of
remission and EFS following autologous transplantation.
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