Health-related quality of life in severe cryoglobulinaemic vasculitis and improvement after B-cell depleting therapy.

Objectives: To study the health-related quality of life (HRQOL) in severe cryoglobulinaemic vasculitis (CV) associated with hepatitis C virus infection (HCV) and to describe the effect of rituximab on HRQOL.

Methods: HRQOL was evaluated with the Medical Outcomes Study Short Form 36 (SF-36). Health Survey questionnaire was submitted to 15 patients with severe CV.

A randomized controlled trial of rituximab for the treatment of severe cryoglobulinemic vasculitis.

Objective: To conduct a long-term, prospective, randomized controlled trial evaluating rituximab (RTX) therapy for severe mixed cryoglobulinemia or cryoglobulinemic vasculitis (CV).

Methods: Fifty-nine patients with CV and related skin ulcers, active glomerulonephritis, or refractory peripheral neuropathy were enrolled. In CV patients who also had hepatitis C virus (HCV) infection, treatment of the HCV infection with antiviral agents had previously failed or was not indicated.

Rheumatoid factor positivity rather than anti-CCP positivity, a lower disability and a lower number of anti-TNF agents failed are associated with response to rituximab in rheumatoid arthritis.

Objectives: We explored clinical factors associated with a major response to rituximab (RTX) (e.g. ACR >/=50, and European League against Rheumatism (EULAR) moderate to good response) in patients with active long-standing RA and inadequate response to anti-TNF agents or traditional DMARDs.

Long-term effects of rituximab in rheumatoid arthritis: clinical, biologic, and pharmacogenetic aspects.

Rituximab selectively targets the B-cell compartment, including rheumatoid factor-positive B cells. Short-term efficacy and safety of rituximab in rheumatoid arthritis (RA) has been established by multicenter randomized placebo-controlled studies. Results of long-term follow-up of the phase II/III clinical trials have confirmed the efficacy and safety of repeated courses of rituximab in the responders.

Multipotent cells can be generated in vitro from several adult human organs (heart, liver, and bone marrow).

The aims of our study were to verify whether it was possible to generate in vitro, from different adult human tissues, a population of cells that behaved, in culture, as multipotent stem cells and if these latter shared common properties. To this purpose, we grew and cloned finite cell lines obtained from adult human liver, heart, and bone marrow and named them human multipotent adult stem cells (hMASCs). Cloned hMASCs, obtained from the 3 different tissues, expressed the pluripotent state-specific transcription factors Oct-4, NANOG, and REX1, displayed telomerase activity, and exhibited a wide range of differentiation potential, as shown both at a morphologic and functional level.

Aberrant expression of TRAIL in B chronic lymphocytic leukemia (B-CLL) cells.

Analysis of peripheral blood (>85% CD19+/CD5+ B) lymphocytes, obtained from 44 patients affected by B chronic lymphoid leukemia (B-CLL), showed that surface TNF-related apoptosis inducing ligand (TRAIL) was expressed in all samples and at higher levels with respect to unfractionated lymphocytes and purified CD19+ B cells, obtained from 15 normal blood donors. Of note, in a subset of B-CLL samples, the addition to B-CLL cultures of a TRAIL-R1-Fc chimera, which binds at high affinity to surface TRAIL, significantly decreased the percentage of viable cells with respect to untreated control B-CLL cells, suggesting that surface TRAIL may play an unexpected role in promoting B-CLL cell survival. In spite of the majority of B-CLL lymphocytes expressed variable surface levels of "death receptors" TRAIL-R1 and TRAIL-R2, the addition in culture of recombinant TRAIL increased (>20% vs.

Antibody binding capacity for evaluation of MDR-related proteins in acute promyelocytic leukemia: Onset versus relapse expression.

Background: Multidrug resistance (MDR) remains a major obstacle for successful treatment in cancer, in particular in acute leukemia. In acute promyelocytic leukemia (APL), the high sensitivity to anthracyclines appears to be attributable to the low frequency of MDR proteins overexpression at onset even if 30% of patients still relapse and become resistant to therapy. In attempt to explain different blast cell sensitivity, we studied the expression of PGP, MRP1, MRP2, and LRP in 45 cases of APL, comparing onset of disease with relapse.

Clinical characteristics, prognostic factors and multidrug-resistance related protein expression in 36 adult patients with acute promyelocytic leukemia.

Unlabelled: We report on a single-center experience about the characteristics and outcome of 36 acute promyelocytic leukemia (APL) patients observed at our Department of Hematology between 1990 and 2002. The expression, of multidrug-resistance (MDR) associated proteins (PGP, LRP, MRP1) was also analyzed. There were 12 males and 24 females (median age 37 yr), 89% (32 of 36) with classic morphology, and 11% (four of 36) with a microgranular variant.

B-cell compartment as the selective target for the treatment of immune thrombocytopenias.

Background And Objectives: Rituximab is a chimeric anti-CD20 monoclonal antibody active against normal and malignant B cells. Treatment with rituximab is associated with the development of a severe (even if transient) B-cell depletion from peripheral blood and lymphatic tissues. These effects could be useful in autoimmune diseases in order to interfere with the production of pathologic antibodies.

CD34+-selected versus unmanipulated autologous stem cell transplantation in multiple myeloma: impact on dendritic and immune recovery and on complications due to infection.

Background: Large-scale CD34+ enrichment has been demonstrated a safe method in autologous transplantation for multiple myeloma. However, the high CD34+ enrichment and the consequent plasma cell purging result in concomitant T-cell and dendritic-cell (DC) depletion, theoretically increasing the risk of life-threatening infections.

Patients And Methods: We evaluated immunological and dendritic reconstitution in 72 myeloma patients who had undergone CD34+-selected (n = 45) and unmanipulated (n = 27) stem cell transplant, and its correlation with infections.

CD56 and PGP expression in acute myeloid leukemia: impact on clinical outcome.

Background And Objectives: Overexpression of P-glycoprotein (PGP), a multidrug-related (MDR) protein, is one of the most important factors responsible for reduced drug sensitivity in acute myeloid leukemia (AML). Recently, we demonstrated that the presence of CD56 antigen, an isoform of the neural adhesion molecule, in AML cells is a negative independent prognostic factor for the achievement of complete remission (CR) and correlates with shorter survival. Since in our previous report we observed a more frequent PGP expression in CD56+ patients, we hypothesized that the reduced response to chemotherapy in this group of patients was due to increased PGP-mediated drug efflux.

Dendritic cell recovery after autologous stem cell transplantation.

There is persistent immunosuppression not only in allogeneic but also in autologous stem cell transplantation because humoral and cellular immunity may take a year or more to return to normal, with increased risk of infectious complications. This immune defect may also involve antigen presentation, in particular dendritic cell (DC) function. We evaluated DC subset reconstitution in 58 patients who underwent bone marrow (BM) or peripheral blood (PB) autologous haematopoietic stem cell transplantation (HSCT).

B-cell depletion with rituximab as treatment for immune hemolytic anemia and chronic thrombocytopenia.

Background And Objectives: Rituximab reacts specifically with the CD20 antigen and induces B-cell depletion. This could interfere with the production of autoantibodies in some immune diseases. The objective of this study was to assess the effects of rituximab in autoimmune hemolytic anemia and thrombocytopenia.

Amifostine does not inhibit the toxic effects of anthracycline derivates or mitoxantrone on MDR tumor cell lines.

In this work three human cell lines with multidrug resistance (MDR) caused by a P-glycoprotein (PGP) overexpression, CEM VLB, HL60 DNR, LOVO DX and two cell lines with MDR associated with a multidrug related protein (MRP) or a lung resistance-related protein (LRP) overexpression named GLC4 ADR and SW1573/2R120 were tested for Amifostine protection against Daunorubicin, Doxorubicin, Idarubicin and Mitoxantrone toxicity. This class of anticancer agents was chosen because they are commonly used in the first line treatments of acute leukemias where a PGP, an LRP or an MRP overexpression often occurs even at onset. A 7-day incubation with escalating doses of anticancer agents with or without a 15 minute preincubation in Amifostine or its active metabolite WR-1065 were used.

P-glycoprotein (PGP), lung resistance-related protein (LRP) and multidrug resistance-associated protein (MRP) expression in acute promyelocytic leukaemia.

We analysed the expression of three drug transporter proteins [p-glycoprotein (PGP), lung resistance-related protein (LRP) and multidrug resistance-associated protein (MRP1)] involved in anthracycline resistance that are frequently overexpressed in poor-risk adult acute non-lymphocytic leukaemia (ANLL), in 23 acute promyelocytic leukaemia (APL) patients at onset managed at a single institution. Cellular daunorubicin accumulation was also evaluated. At onset, no case had PGP or MRP1 expression that exceeded that of non-multidrug-resistant (MDR) cell lines.

Liposome-encapsulated daunorubicin for PGP-related multidrug resistance.

The possibility that Daunoxome (DNX), a combination of daunorubicin (DNR) with a liposomal targeting system, escapes PGP was tested. Two pairs of leukaemic cell lines, each consisting of the parental non-multidrug resistance (MDR) line and of a MDR variant, were studied for cytotoxicity (MTT test) and for cellular DNR kinetic and accumulation (flow cytometry). DNX and free DNR were equally toxic against non-MDR cells, whereas the liposomal anthracycline was more toxic than the free drug against the MDR variant.

P170 (Pgp) expression in leukemic cells after therapeutic exposure to arabinosyl cytosine.

The expression of the mdr-1 gene coding for a transmembrane 170 KD glycoprotein (P170 or PGP) is an important cause of multidrug resistance (MDR). In tumor cells the expression of the gene may vary and there is experimental evidence that it can be induced by exposure to MDR-unrelated agents. We investigated if the therapeutic exposure to Arabinosyl Cytosine (AC) could affect the level of P170 expression in the blast cells of acute non-lymphocytic leukemia (ANLL).

P-glycoprotein, lung resistance-related protein and multidrug resistance associated protein in de novo acute non-lymphocytic leukaemias: biological and clinical implications.

P-glycoprotein (PGP), lung resistance-related protein (LRP) and multidrug resistance associated protein (MRP) expression and the blast cells' intracellular daunorubicin accumulation (IDA) were evaluated in 96 previously untreated cases of de novo acute non-lymphocytic leukaemia (ANLL). 47/96 patients (49%) were classified as PGP+ 44/ 96 (46%) as LRP+, and 8/96 (8%) as MRP+. The more frequent MDR clusters were PGP-/LRP-/MRP- (32/96 cases, 33%) and the PGP+/LRP+/MRP- (27/96 cases, 28%) followed by PGP+/LRP-/MRP- (15/96 cases, 16%) and PGP-/LRP+/MRP- (14/96 cases, 14%).

P-glycoprotein (PGP), and not lung resistance-related protein (LRP), is a negative prognostic factor in secondary leukemias.

Background And Objective: In cell lines, there is an ongoing debate about the role of the lung resistance-related protein (LRP) whereas the role played by P-glycoprotein (PGP) in determining a multidrug resistance is well known. The aim of this study was to evaluate the frequency and the role of a PGP and an LRP overexpression in affecting the intracellular daunorubicin accumulation (IDA) and in predicting the therapy outcome on a subset of overt secondary acute non lymphocytic leukemias (ANLL). An adjunctive point was to evaluate the efficacy of the reversal agent SDZ PSC 833 (PSC) in counteracting impaired IDA.