Novel agents are increasingly used during induction therapy for multiple myeloma (MM), but there is concern about their potential impact on stem cell mobilization. Regimens containing either thalidomide or cyclophosphamide have little or no impact on stem cell collection. In this retrospective review of 136 patients with newly diagnosed MM, we show that the combination of thalidomide and oral CY with dexamethasone (CTD) during induction therapy impaired stem cell mobilization substantially. Compared with VAD (vincristine, doxorubicin, dexamethasone) and a VAD-like induction regimen, the stem cell collection yield after CTD was decreased by 49% (median 5.0 vs 9.8 × 10(6) CD34+cells/kg, P<0.001). Following CTD, more patients failed to mobilize enough stem cells for one (25.4 vs 5.8%, P=0.002) or two (39.4 vs 15.9%, P=0.002) transplants. These results demonstrate that the combination of thalidomide and oral CY impairs stem cell mobilization and indicate that drugs with no previously reported relevant effect on stem cell mobilization can have a substantial impact when given in combination.