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- Title
Feasibility of fludarabine added to VAD during induction therapy in multiple myeloma: a randomised phase II-study.
- Authors
Björkstrand, Bo; Rasmussen, Thomas; Remes, Kari; Gruber, Astrid; Pelliniemi, Tarja-Terttu; Johnsen, Hans E.
- Abstract
Abstract. Multiple myeloma (MM) is considered to be an essentially incurable haematological malignant disease, probably because of the existence of resistant clonal precursor cell with self-renewal capacity. Recent data have indicated that the myeloma cell hierarchy includes circulating clonal memory B cells, which differ considerably from the classical end-stage plasma cells, infiltrating the bone marrow. The pathophysiological significance of these cells is unknown, but hypothetically they may serve as ‘sleeping’ myeloma stem cells responsible for and ‘feeding’ post-treatment relapse and progression. The present study evaluates the toxicity and feasibility of fludarabine, added to the VAD-induction regimen in MM, and investigates the effect on the myeloma cell hierarchy. Nineteen patients were randomised to receive either four cycles of VAD (n = 9) or two cycles of VAD, followed by two cycles of VAD combined with 5 days fludarabine 25 mg/m2 /day i.v. (n = 10). Toxicity evaluation showed more profound neutropenia in the fludarabine-treated patients and two infectious episodes in each study arm: three were fever of unknown origin while one, in the fludarabine-arm, was a local skin infection at the insertion site of the central venous line. Nine of the fludarabine-treated patients responded to treatment (two complete remission, seven partial remission), compared with five responders (all PR) in the control-arm. The effects on the blood circulating myeloma compartments identified an increased reduction of CD19+ B cells and myeloma plasma cells in the fludarabine-arm. In conclusion, adding fludarabine to VAD induction in multiple myeloma is feasible and may be clinically effective by reducing the myeloma clone.
- Subjects
TOXICITY testing; MULTIPLE myeloma; CELLS
- Publication
European Journal of Haematology, 2003, Vol 70, Issue 6, p379
- ISSN
0902-4441
- Publication type
Article
- DOI
10.1034/j.1600-0609.2003.00068.x