Three-step high-dose sequential chemotherapy in patients with newly diagnosed multiple myeloma.
OBJECTIVE
High-dose chemotherapy (HDT) with autologous peripheral blood progenitor cell (PBPC) transplant has been increasingly used for newly diagnosed multiple myeloma (MM) in recent years. Presently available results suggest an improvement in the complete remission rate and survival as compared to conventional chemotherapy. However, there is no plateau in the survival curves, and experiments with new treatment schedules and conditioning regimens are warranted.


METHODS
In a non-randomised controlled trial, 20 patients underwent three-step HDT following conventional vincristine/doxorubicin/dexamethasone (VAD)-based induction. In the intensification phase patients received high-dose cyclophosphamide (HD-CY), high-dose etoposide (HD-VP), and mitoxantrone (NOV) plus melphalan (L-PAM) with haemopoietic rescue. Maintenance treatment with interferon was given until relapse. Actuarial overall survival (OS) and event-free survival (EFS) curves were plotted according to the method of Kaplan and Meier. In five of the eight patients achieving complete remission (CR), the molecular disease was monitored by polymerase chain reaction technique (PCR).


RESULTS
Overall 18/20 (90%) patients responded, with a CR rate of 40%. After an average follow-up of 40 months, median EFS and OS are 25.5 and 44.6 months, respectively. Monoclonal cells were detectable in the post-treatment bone marrow and in the aphereses of the five CR patients monitored by PCR.


CONCLUSIONS
The present three-step HDT regimen, including conditioning with mitoxantrone and melphalan, proved to be feasible and safe. Our results are in agreement with the hypothesis that HDT results in an increased remission rate and in prolonged survival in newly diagnosed MM, but a cure is unlikely.
Ballestrero
Alberto
A
Department of Internal Medicine, University of Genova, Italy.
Ferrando
Fabio
F
Miglino
Maurizio
M
Clavio
Marino
M
Gonella
Roberta
R
Garuti
Anna
A
Grasso
Raffaella
R
Ghio
Riccardo
R
Balleari
Enrico
E
Gobbi
Marco
M
Patrone
Franco
F
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D002999:Clone Cells / Q000473:pathology; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004273:DNA, Neoplasm / Q000032:analysis; D003907:Dexamethasone / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy* / Q000628:therapy; D012074:Remission Induction / Q000379:methods; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
D004273:DNA, Neoplasm; D014750:Vincristine; D005047:Etoposide; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D008942:Mitoxantrone; D008558:Melphalan