New graphic AUC-based method to estimate overall survival benefit: pomalidomide reanalysis.

WHAT IS KNOWN AND OBJECTIVE: Difference in median survival is an erratic measure and sometimes does not provide a good assessment of survival benefit. The aim of this study was to reanalyse the overall survival benefit of pomalidomide from pivotal clinical trial using a new area under curve (AUC)-based method. COMMENT: In the pivotal trial, pomalidomide plus low-dose dexamethasone showed a significant survival benefit over high-dose dexamethasone, with a difference between medians of 4.6 months. The new AUC method applied to the survival curves, obtained an overall survival benefit of 2.6 months for the pomalidomide treatment. This average difference in OS was calculated for the 61.5% of patients for whom the time to event is reliable enough. WHAT IS NEW AND CONCLUSION: This 2-month differential would have major clinical and pharmacoeconomic implications, on both cost-effectiveness studies and on the willingness of the healthcare systems to pay for this treatment.

[Erythropoietin: a study of its use in oncohematology]. / Eritropoyetina: estudio de utilización en oncohematología.

OBJECTIVE: To assess the effectiveness of erythropoietin (EPO) in a Clinical Oncohematology Unit within a general hospital, and to propose a therapeutic algorithm with EPO based on recommendations by ASCO. MATERIAL AND METHODS: A descriptive, retrospective study was carried out on patients who required support treatment with EPO while in the Oncohematology Unit during the year 2001. Data were collected by reviewing patient medical records. An effective treatment was defined as an increase in baseline hemoglobin (Hb) equal to or higher than 2 g/dL over 4-8 weeks, with no transfusion requirements or decreased transfusion needs. Baseline Hb values, their distribution per diagnosis, and the involvement of platinum-containing chemotherapy regimens were analyzed. RESULTS: Of the 353 patients in chemotherapy, 87% corresponded to oncologic diagnoses while the rest had hematological neoplasms. A total of 54 patients were assessed, with 83% of these corresponding to the oncologic area. Oncologic diagnoses that most required the use of EPO included: head-neck 53%, genitourinary 39%, and lung 39%. Overall effectiveness was 57% (60% in oncology and 44% in hematology). The Hb value leading to initial prescription (baseline Hb) was always below 10 g/dL for the hematology area, whereas most oncology patients exhibited higher levels at therapy onset. CONCLUSIONS: 1. Its percentage of failure: 40% for oncology and 56% for hematology patients, together with its high cost, shows that a further search for predictive factors is warranted in order to more precisely select individuals who may benefit from this therapy. 2. The percentage of oncology patients with baseline Hb <10 is only 29%. Baseline Hb values for treatment onset and peak Hb values for therapy discontinuation should be agreed upon. Treatment initiation when Hb values fall below 10 g/dL would be a reasonable option, and a decision to use EPO above 10 g/dL should be made in patients with less severe anemia (10-12 g/dL) only if clinical circumstances render it advisable. 3. Use protocols must include clear concept definitions for treatment, and for primary and secondary prophylaxis, which will help in the establishment of therapeutic algorithms.

Chimeric synthetic peptides containing two immunodominant epitopes from the envelope gp46 and the transmembrane gp21 glycoproteins of HTLV-I virus.

Two chimeric synthetic peptides incorporating immunodominant sequences from HTLV-I virus were synthesized. Monomeric peptides P7 and P8 represent sequences from transmembrane protein (gp21) and envelope protein (gp46) of the virus. The peptide P7 is a gp21 (374-400) sequence and the peptide P8 is a gp46 (190-207) sequence. Those peptides were arranged in a way that permits one to obtain different combinations of chimeric peptides (P7-GG-P8 and P8-GG-P7), separated by two glycine residues as spacer arms. The antigenic activity of these peptides were evaluated by UltramicroEnzyme-linked immunosorbent assay (UMELISA) by using panels of anti-HTLV-I-positive sera (n = 22), anti-HTLV-I/II-positive sera (n = 2), HTLV-positive (untypeable) serum samples (n = 2), and anti-HTLV-II-positive sera (n = 11), while specificity was evaluated with anti-HIV-positive samples (n = 19) and samples from healthy blood donors (n = 30). The efficacy of the chimeric peptides in solid-phase immunoassays was compared with the monomeric peptides and monomeric peptides together. The chimeric peptide P7-GG-P8 proved to be the most reactive with anti-HTLV-I-positive sera. These results may be related to a higher peptide adsorption capacity to the solid surface and for epitope accessibility to the antibodies. This chimeric peptide would be very useful for HTLV-I diagnostics.

Chimeric synthetic peptides from the envelope (gp46) and the transmembrane (gp21) glycoproteins for the detection of antibodies to human T-cell leukemia virus type II.

Two chimeric synthetic peptides incorporating immunodominant sequences from HTLV-II virus were synthesized. Monomeric peptides P2 and P3 represent sequences from transmembrane protein (gp21) and envelope protein (gp46) of the virus. The peptide P2 is a gp21 (370-396) sequence and the peptide P3 is a gp46 (178-205) sequence. Those peptides were arranged in a way that permits one to obtain different combinations of chimeric peptides (P2-GG-P3 and P3-GG-P2), separated by two glycine residues as spacer arms. The antigenic activity of these peptides was evaluated by UltramicroEnzyme-linked immunosorbent assay (UMELISA) by using panels anti-HTLV-II-positive sera (n = 11), anti-HTLV-I/II-positive sera (n = 2), HTLV-positive (untypeable) serum samples (n = 2), and anti-HTLV-I-positive sera (n = 22), while specificity was evaluated with anti-HIV-positive samples (n = 19) and samples from healthy blood donors (n = 30). The efficacy of the chimeric peptides in solid-phase immunoassays was compared with the monomeric peptides and a mixture of the monomeric peptides. Higher sensitivity was observed for chimeric peptide Q5 assay. Those results may be related to a higher peptide adsorption capacity to the solid surface and for epitope accessibility to the antibodies. This chimeric peptide would be very useful for HTLV-II diagnostic.