The combination of melphalan-prednisone-thalidomide (MPT) has been investigated in several clinical studies that differed significantly with regard to patient characteristics and treatment schedules. This prospective trial differs from previous melphalan-prednisone (MP) vs. MPT trials by treatment dosing, duration, routine anticoagulation, and permission for a crossover. Newly diagnosed patients with multiple myeloma (MM) (n=122) aged greater than 55 yr, not eligible for transplantation were randomized to receive 8 cycles of M (9 mg/m(2) /d) and P (60 mg/m(2) /d) for 4d every 6 wk (n=62) or MP and thalidomide (100 mg/d) continuously (n=60). Primary endpoint was treatment response and toxicities following 4 and 8 cycles of therapy. Secondary endpoints were disease-free (DFS) and overall survival (OS). Overall, MPT-treated patients were younger (median 69 yr vs. 72 yr; P=0.016) and had a higher incidence of renal impairment (RI, 19% vs. 7%, respectively; P=0.057). After 4 cycles of treatment (n=115), there were more partial responses or better in the MPT arm than in the MP arm (57.9% vs. 37.5%; P=0.030). However, DFS and OS were not significantly different between the arms after a median of 23 months follow-up (median OS 26.0 vs. 28.0 months, P=0.655; DFS 21.0 vs. 14.0 months, P=0.342, respectively). Crossover to MPT was required in 11 patients, 57% of whom responded to treatment. A higher rate of grade 3-4 infections was observed in the MPT arm compared with the MP arm (22.4% vs. 7.0%; P=0.033). However, none of these infections were associated with febrile neutropenia. Death within the first 3 months was observed more frequently in the MP arm (n=8, 14.0%) than in the MPT arm (n=2, 3.4%; P=0.053). Long-term discontinuation and dose reduction rates were also analyzed (MPT: 15.5% vs. MP: 5.3%; P=0.072). Although patients treated with MPT were relatively younger and had more frequent RI, better responses and less early mortality were observed in all age groups despite more frequent discontinuation.

The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits.

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Summary. To date, no randomized study has compared different doses of recombinant human granulocyte colonystimulating factor (rhG-CSF) following submyeloablative mobilization chemotherapy. Therefore, we evaluated the effect of different doses of rhG-CSF following mobilization chemotherapy on yields of CD34 + peripheral blood stem cells (PBSC). Fifty patients were randomized to receive 8 (n 25) versus 16 lg/kg/d (n 25) of rhG-CSF following mobilization chemotherapy. The median number of CD34 + cells collected after 8 lg/kg/d of rhG-CSF was 2á36´10 6 /kg (range, 0á21±7á80), compared with 7á99 (2á76±14á89) after 16 lg/kg/d (P < 0á001). Twenty out of 25 (80%) patients in the low-dose and 23 out of 25 (92%) in the high-dose rhG-CSF arm underwent high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). Median days to white blood cell engraftment in patients mobilized with 8 lg/kg and 16 lg/kg of rhG-CSF were 12 (10±20) and 9 (8±11) respectively (P < 0á001). There was no difference between the two groups regarding the other parameters of peritransplant morbidity: days to platelet engraftment (P 0á10), number of red blood cell (P 0á56) and platelet transfusions (P 0á22), days of total parenteral nutrition requirement (P 0á84), fever (P 0á93) and antibiotics (P 0á77), and number of different antibiotics used (P 0á58). These data showed that higher doses of rhG-CSF following submyeloablative mobilization chemotherapy were associated with a clear dose±response effect based on the collected cell yields. Based on the parameters of peritransplant morbidity, 8 lg/kg/d was as effective as 16 lg/kg/d except for a rapid neutrophil engraftment in the high-dose arm. Therefore, in routine clinical practice, despite some advantage in the use of higher doses of rhG-CSF, lower doses may be used for PBSC collections following chemotherapy-based mobilization regimens in this cost-conscious era.

Summary. This study evaluated of the effect of post-transplant recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration on the parameters of peritransplant morbidity. Three sequential and consecutive cohorts of 20 patients each received either post-transplant rhG-CSF at a dose of 5 lg/kg/d i.v. in the morning, starting on d 0, d 5, or no rhG-CSF. Patients who received rhG-CSF starting on d 0 and 5 recovered granulocytes more rapidly than those not receiving rhG-CSF (P < 0AE001 for ANC ‡ 0AE5 and 1 · 10 9 /l). RhG-CSF administration was not significantly associated with more rapid platelet engraftment. RhG-CSF administration starting on d 0 and 5 was significantly associated with a decreased duration of fever (P ¼ 0AE002 and 0AE001 respectively), antibiotic administration (P < 0AE001 and 0AE006 respectively) and shorter hospitalization (P < 0AE001 and 0AE001 respectively) compared with the reference group. There was no difference between the d 0 and d 5 arms regarding the parameters of peritransplant morbidity. In conclusion, rhG-CSF administration was associated with a faster granulocyte recovery, shorter hospitalization, and shorter period of fever and nonprophylactic antibiotic administration. This study also showed that starting rhG-CSF administration on d 5 may be as effective as d 0 on the clinical outcome and may be an economical approach in routine clinical practice in this costconscious era.