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

R. Fenk, P. Schneider, M. Kropff, A. N. Huenerlituerkoglu, Ulrich G. Steidl, C. Aul, B. Hildebrandt, R. Haas, A. Heyll, G. Kobbe

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

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 ≥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.

Original languageEnglish (US)
Pages (from-to)588-594
Number of pages7
JournalBritish Journal of Haematology
Volume130
Issue number4
DOIs
StatePublished - Aug 2005
Externally publishedYes

Fingerprint

Idarubicin
Melphalan
Stem Cell Transplantation
Multiple Myeloma
Cyclophosphamide
Mortality
Arm
Confidence Intervals
Therapeutics
Transplants
Drug Therapy
Survival
Infection

Keywords

  • Autologous transplantation
  • High-dose therapy
  • Multiple myeloma
  • Randomised trial

ASJC Scopus subject areas

  • Hematology

Cite this

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. / Fenk, R.; Schneider, P.; Kropff, M.; Huenerlituerkoglu, A. N.; Steidl, Ulrich G.; Aul, C.; Hildebrandt, B.; Haas, R.; Heyll, A.; Kobbe, G.

In: British Journal of Haematology, Vol. 130, No. 4, 08.2005, p. 588-594.

Research output: Contribution to journalArticle

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abstract = "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 ≥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.",
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