ABSTRACT
Mantle cell lymphoma (MCL) accounts for 3-10% of all non-Hodgkin's lymphomas, with median overall survival not exceeding 3-4 years. Rituximab in combination with the Hyper-CVAD regimen appears the most promising regimen; thus, we adopted it as a first-line treatment strategy in a series of 24 patients. In addition to evaluation of clinical success of the regimen, we investigated a possible role of polymorphism in IgG Fc receptors, FCgammaRIIIa and FCgammaRIIa. The frequencies of FCgammaRIIIa-158 were as follows: V/V=4/24 (17%); V/F=16/24 (66%); F/F=4/24 (17%). Those of the FCgammaRIIa-131 polymorphism were H/H=11/24 (46%), H/R=9/24 (37%), R/R=4/24 (17%). The overall response rate was 62.5%, with 33% of complete responses (CRs) after four cycles of R-Hyper-CVAD. Two-year progression-free survival (PFS) was 78% for 158V/V patients vs 75% for cases carrying phenylalanine (p=0.88). When the FCgammaRIIa polymorphism was assessed, the 2-year PFS was 82% for 131H/H patients vs 75% for those carrying arginine (p=0.26). Eighty-three percent of cases achieved Polymerase Chain Reaction (PCR)-negativity: the progression rate was significantly influenced by the minimal residual disease clearance, with 12% progression in the subgroup of PCR-negative cases versus 67% progression in PCR-positive cases (p=0.008). The achievement of PCRnegativity was not significantly influenced by FCgammaR polymorphisms. Results confirm that rituximab plus Hyper-CVAD is an effective regimen for the induction of prolonged remission in patients with aggressive MCL and suggest that rituximab efficacy is independent of the FCgammaR polymorphisms.
Subject(s)
Antigens, CD/genetics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Mantle-Cell/drug therapy , Receptors, IgG/genetics , Adult , Aged , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal, Murine-Derived , Cyclophosphamide/therapeutic use , Dexamethasone/therapeutic use , Disease-Free Survival , Doxorubicin/therapeutic use , Female , Humans , Male , Middle Aged , Polymerase Chain Reaction , Polymorphism, Genetic , Prospective Studies , Rituximab , Vincristine/therapeutic useABSTRACT
AIM: Several neutrophil functions can be modified by rhG-CSF administration. Neutrophil morphology changes in the course of treatment with Filgrastim (nonglycosylated rhG-CSF), along with impairment of chemotaxis. Both morphology and chemotaxis are not affected by treatment with Lenograstim (glycosylated rhG-CSF). Thus, we evaluated actin polymerization in neutrophils induced by treatment with the two forms of rhG-CSF. In fact, actin polymerization is crucial for neutrophil motility. MATERIALS AND METHODS: We evaluated twelve healthy subjects undergoing peripheral blood stem cells (PBSC) mobilization for allogeneic transplantation to HLA-identical siblings. Neutrophils were isolated by peripheral venous blood before and after administration of either Filgrastim (six PBSC donors) or Lenograstim (six PBSC donors). Actin polymerization was investigated by a flow cytometric assay, using FITC-phalloidin as a specific probe for F-actin, and two parameters were measured: spontaneous actin polymerization in resting neutrophils; fMLP-stimulated actin polymerization. Results were expressed as relative F-actin content. Fifteen blood donors were studied as a control group. RESULTS: Filgrastim administration induced an increased relative F-actin content in resting neutrophils; however, no further actin polymerization was observed after fMLP stimulation. Neutrophils from subjects treated with Lenograstim showed a normal behaviour in terms of both spontaneous and stimulated actin polymerization. CONCLUSIONS: Glycosylated and nonglycosylated rhG-CSF differently affect actin polymerization in newly generated neutrophils. Such effects may explain some previous findings concerning both morphology and chemotactic properties and may be due to different effects of the two forms of rhG-CSF on proteins involved in neutrophil motility regulation.
Subject(s)
Actins/drug effects , Actins/metabolism , Granulocyte Colony-Stimulating Factor/pharmacology , Neutrophils/drug effects , Neutrophils/metabolism , Adult , Case-Control Studies , Female , Filgrastim , Flow Cytometry , Glycosylation , Hematopoietic Stem Cell Mobilization , Humans , Lenograstim , Male , Middle Aged , Polymers , Recombinant Proteins/pharmacologyABSTRACT
The aim of the paper is to present some of the characteristics of the compensation systems in EEC countries and to focus on the compensation of asbestos-related diseases: for each country the diseases admitted for compensation, the date of introduction into the schedule, the number of compensations awarded and a comparison between compensations for mesothelioma and mortality are presented. The data have been collected in 1990-91 by asking for information to the Compensation Institutes. The results suggest that the objective of harmonisation of the compensation systems among European countries is far from being achieved and needs re-vitalisation. The gap between knowledge and public health action has been considerable in the compensation of asbestos-related diseases, especially in the compensation of cancers. The results confirm, therefore, from a different perspective the validity of considering asbestos as a case study in public health. Finally, the Authors stress the serious situation in Italy with respect to updating the list of prescribed diseases as epidemiological data are available and to compensating occupationally related asbestos diseases.
