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The treatment of multiple myeloma has undergone significant changes in the recent past. The arrival of novel agents, especially thalidomide, bortezomib and lenalidomide, has expanded treatment options and patient outcomes are improving significantly. This article summarises the discussions of an expert meeting which was held to debate current treatment practices for multiple myeloma in Switzerland concerning the role of the novel agents and to provide recommendations for their use in different treatment stages based on currently available clinical data. Novel agent combinations for the treatment of newly diagnosed, as well as relapsed multiple myeloma are examined. In addition, the role of novel agents in patients with cytogenetic abnormalities and renal impairment, as well as the management of the most frequent side effects of the novel agents are discussed. The aim of this article is to assist in treatment decisions in daily clinical practice to achieve the best possible outcome for patients with multiple myeloma.

BACKGROUND Sensitization of leukemic cells with hematopoietic growth factors may enhance the cytotoxicity of chemotherapy in acute myeloid leukemia (AML). METHODS In a multicenter randomized trial, we assigned patients (age range, 18 to 60 years) with newly diagnosed AML to receive cytarabine plus idarubicin (cycle 1) and cytarabine plus amsacrin (cycle 2) with granulocyte colony-stimulating factor (G-CSF) (321 patients) or without G-CSF (319). G-CSF was given concurrently with chemotherapy only. Idarubicin and amsacrin were given at the end of a cycle to allow the cell-cycle-dependent cytotoxicity of cytarabine in the context of G-CSF to have a greater effect. The effect of G-CSF on disease-free survival was assessed in all patients and in cytogenetically distinct prognostic subgroups. RESULTS After induction chemotherapy, the rates of response were not significantly different in the two groups. After a median follow-up of 55 months, patients in complete remission after induction chemotherapy plus G-CSF had a higher rate of disease-free survival than patients who did not receive G-CSF (42 percent vs. 33 percent at four years, P=0.02), owing to a reduced probability of relapse (relative risk, 0.77; 95 percent confidence interval, 0.61 to 0.99; P=0.04). G-CSF did not significantly improve overall survival (P=0.16). Although G-CSF did not improve the outcome in the subgroup with an unfavorable prognosis, the 72 percent of patients with standard-risk AML benefited from G-CSF therapy (overall survival at four years, 45 percent, as compared with 35 percent in the group that did not receive G-CSF [relative risk of death, 0.75; 95 percent confidence interval, 0.59 to 0.95; P=0.02]; disease-free survival, 45 percent vs. 33 percent [relative risk, 0.70]; 95 percent confidence interval, 0.55 to 0.90; P=0.006). CONCLUSIONS Sensitization of leukemic cells with growth factors is a clinically applicable means of enhancing the efficacy of chemotherapy in patients with AML.

The clinical use of autologous marrow transplantation in acute myeloid leukemia (AML) has been hampered by the inability to collect adequate numbers of cells after remission induction chemotherapy and the notably delayed hematopoietic regeneration following autograft reinfusion. Here we present a study in which the feasibility of mobilizing stem cells was investigated in newly diagnosed AML, Among 96 AML patients, 76 patients (79%) entered complete remission. Mobilization was undertaken with low dose and high dose schedules of G-CSF in 63 patients, and 54 patients (87%) were leukapheresed. A median of 2.0 x 10(6) CD34(+) cells/kg (range 0.1-72.0) was obtained in a median of three leukaphereses following a low dose G-CSF schedule (150 mu g/m(2)) during an average of 20 days. Higher dose regimens of G-CSF (450 mu g/m(2) and 600 mu g/m(2)) given during an average of 11 days resulted in 28 patients in a yield of 3.6 x 10(6) CD34(+) cells/kg (range 0-60.3) also obtained following three leukaphereses. The low dose and high dose schedules of G-CSF permitted the collection of 2 x 10(6) CD34-positive cells in 46% and 79% of cases respectively (P=0.01). Twenty-eight patients were transplanted with a peripheral blood stem cell (PBSC) graft and hemopoietic repopulation was compared with the results of a previous study with autologous bone marrow. Recovery of granulocytes (>0.5 x 10(9)/l, 17 vs 37 days) and platelets (>20 x 10(9)/l; 26 vs 96 days) was significantly faster after peripheral stem cell transplantation compared to autologous bone marrow transplantation. These results demonstrate the feasibility of PBSCT in the majority of cases with AML and the potential advantage of this approach with respect to hemopoietic recovery.

Purpose: The hematopoietic growth factors (HGFs) introduced into induction chemotherapy (CT) of acute myeloid leukemia (AML) might be of benefit to treatment outcome by at least two mechanisms. HGFs given on days simultaneously with CT might sensitize the leukemic cells and enhance their susceptibility to CT. HGFs applied after CT might hasten hematopoietic recovery and reduce morbidity or mortality. Materials and Methods: We set out to evaluate the use of granulocyte-macrophage colony-stimulating factor (GM-CSF; 5 mu g/kg) in a prospective randomized study of factorial design (yes or no GM CSF during CT, and yes or no GM-CSF after CT) in patients aged 15 to 60 years (mean, 42) with newly diagnosed AML. GM-CSF was applied as follows: during CT only (+/-, n = 64 assessable patients), GM-CSF during and following CT (+/+, n = 66), no GM-CSF (-/-, n = 63), or GM-CSF after CT only (-/+, n = 60). Results: The complete response (CR) rate wets 77%. At a median follow-up time of 42 months, probabilities of overall survival (OS) and disease-free survival (DFS) at 3 years were 38% and 37% in all patients. CR rates, OS, and DFS did not differ between the treatment groups (intention-to-treat analysis). Neutrophil recovery (1.0 x 10(9)/L) and monocyte recovery were significantly faster in patients who received GM-CSF after CT (26 days v 30 days; neutrophils, P