Cyclosporin A combined with vincristine, doxorubicin and dexamethasone (VAD) compared with VAD alone in patients with advanced refractory multiple myeloma: an EORTC-HOVON randomized phase III study (06914).

Patients with multiple myeloma (MM) refractory to alkylating agents frequently express P-glycoprotein (Pgp), which is associated with the multidrug resistance (MDR) phenotype. We have conducted a randomized phase II/III study of the MDR reversal agent cyclosporin A combined with VAD (vincristine, doxorubicin, dexamethasone) compared with standard VAD in patients with MM stage IIA/IIIA who were refractory to or progressive after treatment with alkylating agents. Out of 81 patients who were randomized, 75 were eligible and evaluable: 34 in the VAD + cyclosporin A arm versus 41 in the VAD arm.

Influence of cytokines and autologous lymphokine-activated killer cells on leukemic bone marrow cells and colonies in AML.

We have already shown that cytokine cocktails (IL-1beta, IL-3, IL-6, SCF, GM-CSF) and/or lymphokine-activated killer (LAK) cells can reduce the amounts of clonal, CD34-positive mononuclear bone marrow cells (BM-MNC) in acute myeloid leukemia (AML). In addition, the influence of those cocktails and/or LAK cells on the clonogenic potential of AML BM-MNC was investigated. BM colonies cultured in agar during different stages of the disease were immunophenotyped in situ: 17 patients at diagnosis, 14 patients in complete remission, 8 patients at relapse, 8 healthy donors.

Lymphokine-activated killer (LAK) cells and cytokines synergize to kill clonal cells in acute myeloid leukemia (AML) in vitro.

We studied the influence of autologous lymphokine-activated-killer (LAK) cells on the survival of clonal and CD34-positive bone marrow (BM) cells from patients with acute myeloid leukemia (AML) in a coculture assay in vitro. (1) LAK cells were grown in the presence of IL-2, in some cases additionally with IL-6. (2) These cytotoxic cells were cocultured with (untreated or cytokine pretreated) AML-BM cells obtained at different stages of the disease.

Cytokines can reduce clonal, CD34-positive cells in acute myeloid leukemia in vitro.

We studied the influence of cytokine mixes on the survival of acute myeloid leukemia (AML) bone-marrow (BM) cells in a 14-day culture assay in vitro. Southern-blot analysis using a panel of different probes in combination with densitometry and flow cytometry were used to detect and compare the amount of clonal or CD34-positive BM cells before and after the culturing procedure. A significant reduction of CD34-positive cells after incubation with a cytokine mix [interleukin (IL)-1beta, IL-3, IL-6, stem cell factor (SCF), erythropoietin (EP) with granulocyte macrophage/colony-stimulating factor (GM-CSF, Cytok1) could be achieved in all 16 cases with a CD34-positive blast phenotype studied at diagnosis (P<0.