High-dose idarubicin, cyclophosphamide and melphalan as conditioning for autologous stem cell transplantation increases treatment-related mortality in patients with multiple myeloma: results of a randomised study.
We conducted a randomised trial comparing an intensified versus a standard conditioning regimen for high-dose chemotherapy followed by autologous stem-cell transplantation in patients with multiple myeloma. In this study, 56 patients were randomly assigned for high-dose therapy with melphalan 200 mg/m2 or with idarubicin 42 mg/m2, melphalan 200 mg/m2 and cyclophosphamide 120 mg/kg. The primary objective was response rate. Acute toxicity, mainly because of infections, was higher in the intensified treatment arm with a treatment-related mortality of 20% versus 0% in the standard arm. This lead to the early discontinuation of the study. Response rates did not differ significantly between both treatment arms {intensified versus standard: complete response+near complete remission 50% [95% confidence interval (CI) 26-74%] vs. 33% (95% CI 17-55%), partial remission 35% (95% CI 16-61%) vs. 50% (95% CI 30-70%)}. After a follow-up of 5 years, the median time-to-progression and overall survival were not significantly different between both patient groups. Analysis restricted to patients surviving the first 100 d after transplant showed a better outcome for patients with >or=2 bad prognostic risk factors in the intensified treatment arm, however all treatment-related deaths occurred within this group of patients. In conclusion, intensified conditioning for high-dose therapy had intolerably high toxicity without improving outcome in patients with multiple myeloma.
Fenk
R
R
Department of Haematology, Oncology and Clinical Immunology, Heinrich-Heine University, Duesseldorf, Germany. fenk@med.uni-duesseldorf.de
Schneider
P
P
Kropff
M
M
Huenerlituerkoglu
A N
AN
Steidl
U
U
Aul
C
C
Hildebrandt
B
B
Haas
R
R
Heyll
A
A
Kobbe
G
G
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000276:immunology / Q000601:surgery*; D011379:Prognosis; D012074:Remission Induction; D012307:Risk Factors; D033581:Stem Cell Transplantation / Q000401:mortality*; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000009:adverse effects* / Q000379:methods
D003520:Cyclophosphamide; D008558:Melphalan; D015255:Idarubicin