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.
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.
Institute of Hematology and Medical Oncology Seràgnoli, University of Bologna, Via Massarenti 9-40138 Bologna, Italy.
Simona
S
Soverini
Michele
M
Cavo
Claudia
C
Cellini
Carolina
C
Terragna
Elena
E
Zamagni
Deborah
D
Ruggeri
Nicoletta
N
Testoni
Patrizia
P
Tosi
Antonio
A
De Vivo
Marilina
M
Amabile
Tiziana
T
Grafone
Emanuela
E
Ottaviani
Barbara
B
Giannini
Delia
D
Cangini
Francesca
F
Bonifazi
Antonino
A
Neri
Sonia
S
Fabris
Sante
S
Tura
Michele
M
Baccarani
Giovanni
G
Martinelli
D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11; D002882:Chromosomes, Human, Pair 13; D003131:Combined Modality Therapy; D019938:Cyclin D1 / Q000235:genetics*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage*; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage*; D005260:Female; D015870:Gene Expression; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D011237:Predictive Value of Tests; D011379:Prognosis; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000592:standards; D012680:Sensitivity and Specificity; D014750:Vincristine / Q000008:administration & dosage*
D018906:Antineoplastic Agents, Alkylating; D019938:Cyclin D1; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D008558:Melphalan