Three-step high-dose sequential chemotherapy in patients with newly diagnosed multiple myeloma Ballestrero A, Ferrando F, Miglino M, Clavio M, Gonella R, Garuti A, Grasso R, Ghio R, Balleari E, Gobbi M, Patrone F. Three-step high- dose sequential chemotherapy in patients with newly diagnosed multiple myeloma. Eur J Haematol 2002: 68: 101–106. # Blackwell Munksgaard 2002. Abstract: Background and objectives: 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. Design and methods: In a non-randomised controlled trial, 20 patients underwent three-step HDT following conventional vineristine/doxo ulicin/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. Conclusion: 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. Alberto Ballestrero 1,2 , Fabio Ferrando 1,2 , Maurizio Miglino 1,2 , Marino Clavio 1,2 , Roberta Gonella 1,2 , Anna Garuti 1,2 , Raffaella Grasso 1,2 , Riccardo Ghio 2 , Enrico Balleari 1 , Marco Gobbi 1,2 , Franco Patrone 1,2 1 Department of Internal Medicine (Di.M.I.), University of Genova and 2 Department of Hematology and Oncology, Azienda Ospedaliera Ospedale San Martino e Cliniche Universitarie Convenzionate, Genova, Italy Key words: multiple myeloma; high-dose chemotherapy; peripheral blood progenitor cell; autologous transplantation Correspondence: Prof.Franco Patrone, Department of Internal Medicine, University of Genova, Viale Benedetto XV no. 6,16132 Genova, Italy Tel:+39 010 3538952 Fax: +39 010 3538650 e-mail: fpatrone@unige.it Accepted for publication 29 January 2002 High-dose chemotherapy (HDT) has been increas- ingly used in the treatment of multiple myeloma (MM) over the past 15 yr, and availabledata suggest that it represents a significant improvement in the treatmentof patientsaged 65 yror less. The results of one randomised and two large non- randomised comparative trials, as well as some uncontrolled phase II studiessuggestthat the outcomeof patientsreceivingHDT for newly diagnosed stage II–III multiple myeloma is better than the outcome ofthe onesreceiving conven- tional chemotherapy. In fact, a higher complete remission (CR)rate wasreported,and this was associatedwith longer remissionand survival (1–6).However,despite these results, there is no plateau in thesurvivalcurves.Therefore,HDT would seem to prolong the natural history of myeloma,although virtuallyevery patient will eventually relapse and die of the disease. Relapse may be due to a few residual tumour cells escaping therapy.These cells can only be detectedby sensitivemethodssuch as amplification of the clonogenic immunoglobulin heavy-chain variable/ diversity/joining (VDJ) gene rearrangement. Eur J Haematol 2002: 68: 101–106 Printed in UK. All rights reserved Copyright # Blackwell Munksgaard 2002 EUROPEAN JOURNAL OF HAEMATOLOGY ISSN 0902-4441 101