The role of thalidomide for previously untreated elderly patients with multiple myeloma remains unclear. Six randomized controlled trials, launched in or after 2000, compared melphalan and prednisone alone (MP) and with thalidomide (MPT). The effect on overall survival (OS) varied across trials. We carried out a meta-analysis of the 1685 individual patients in these trials. The primary endpoint was OS, and progression-free survival (PFS) and 1-year response rates were secondary endpoints. There was a highly significant benefit to OS from adding thalidomide to MP (hazard ratio ‫؍‬ 0.83; 95% confidence interval 0.73-0.94, P ‫؍‬ .004), representing increased median OS time of 6.6 months, from 32.7 months (MP) to 39.3 months (MPT). The thalidomide regimen was also associated with superior PFS (hazard ratio ‫؍‬ 0.68, 95% confidence interval 0.61-0.76, P < .0001) and better 1-year response rates (partial response or better was 59% on MPT and 37% on MP). Although the trials differed in terms of patient baseline characteristics and thalidomide regimens, there was no evidence that treatment affected OS differently according to levels of the prognostic factors. We conclude that thalidomide added to MP improves OS and PFS in previously untreated elderly patients with multiple myeloma, extending the median survival time by on average 20%. (Blood.

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 interaction between multiple myeloma (MM) cells and the bone marrow stroma constitutes the basis of myeloma pathogenesis and has led the way for the corresponding therapeutic strategies. The aim of this study is to evaluate tumor-associated macrophages (TAMs) which is an important element of bone marrow stroma and its prognostic relevance in newly diagnosed MM patients. We also wanted to determine the association between TAMs and microvessel density (MVD). Sixty-eight patients, who were diagnosed with MM at the Department of Hematology, Gazi University Hospital, between January 2000 and January 2011, were reviewed retrospectively. Tumor-associated macrophages were evaluated by staining with anti-CD68 and anti-CD163 monoclonal antibodies, and MVD was evaluated by factor VIII staining. Median age was 60 (range, 40-84) years with 36 males and 32 females. The number of both CD 68+ and CD 163+ cells had a negative impact on OS at 6 years (p = 0.013 vs. 0.036; p = 0.015 vs. 0.039) in univariate and multivariate analysis in which age, sex, ISS, the induction treatment, and response to induction treatment are included as variables. High-grade MVD was found to be associated with increased CD163+ cell count. In conclusion, TAMs seems to be a promising prognostic histopathological marker in newly diagnosed MM patients.

PET/CT allows identification of high-risk myeloma patients, and extramedullary lesions with the highest SUV(max) independently predict inferior OS.

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.