Ticlopidine-induced aplastic anemia (TIAA) is considered very uncommon. We present two new cases, and we review 55 additional cases from the literature. The first case concerns a 70-year-old man who developed severe aplastic anemia 7 weeks after treatment with 500 mg of ticlopidine daily. The patient sustained a severe septic episode, was treated with antibiotics and GM-CSF, and recovered the 14 th day after ticlopidine withdrawal. The second was an 82-year-old man receiving ticlopidine for 2 years when, during a febrile episode, he was found neutropenic with marrow aplasia. Ticlopidine withdrawal and treatment with antibiotics, transfusions, and G-CSF helped him to recover. When the data of the 57 patients are evaluated, a reversible direct cytotoxic effect of ticlopidine on the pluripotent/bipotent hematopoietic progenitor stem cell is proposed. It is estimated that the real incidence if TIAA is higher, and many cases, initially presented as agranulocytosis ± thrombocytopenia, might be true aplastic anemias, not proven by marrow aspiration or trephine biopsy. There is no effective monitoring to prevent this side effect. Recombinant growth factors appear not to help in shortening the neutropenic period.
We determined nine immune function parameters at diagnosis in patients with myelodysplastic syndromes (MDS) and correlated the results with the FAB classification and prognosis by univariate and multivariate analyses. Patients with refractory anaemia (RA) and refractory anaemia with ring sideroblasts (RAS) tended to have a higher CD4/CD8 ratio and a lower amount of γ‐globulins and soluble interleukin‐2 receptors in serum in comparison to those suffering from the other three subgroups of MDS. FAB classification, neutrophil and CD8 + T‐cell number had the best discriminatory capacity for predicting survival less than 1 year, and FAB classification, neutrophil number and serum TNF levels were predictors for conversion to acute leukaemia. The frequent occurrence of infections, on the other hand, could be better predicted by the absolute numbers of neutrophils and CD4 + cells and by the skin test score.
According to the widely accepted myeloma staging system, the bulk of paraprotein is the main determinant of disease stage. However, myelomatous plasma cells differ considerably in their ability to synthesize and secrete monoclonal paraprotein. We determined plasma cell secreting potential (PCSP) as the amount of M-component, divided by the percentage of marrow plasmacytic infiltration, in 240 patients with myeloma, and correlated our results with chain isotype, plasma cell morphology, severity of bone disease, well-recognized prognostic factors, such as serum LDH, CRP, albumin and beta2-microglobulin, treatment response and overall survival. PCSP was higher in IgG than in other myeloma types, and was an almost constant parameter for each individual patient, in 134/166 cases. A > 10% decrease of PCSP in 26 patients was associated with disease aggressiveness and treatment failure. Patients with MGUS had significantly higher PCSP than those with myeloma of the same chain type. Higher PCSP was associated with stage I, absence of Bence-Jones proteinuria and indolent forms of disease with lower proliferating cell nuclear antigen (PCNA) positivity, serum LDH, alpha2-globulins, CRP and beta2-microglobulin and higher albumin levels. Conversely, patients with immature/plasmablastic morphology and those with severe bone disease had lower PCSP. Good responders to treatment had significantly higher PCSP than moderate and poor responders and PCSP was strongly correlated with overall survival in IgG and IgA myeloma. In conclusion, PCSP reflects the maturation status of myelomatous cells and therefore can be used as a prognostic factor, since patients with high secreting potential represent a lower malignancy group, in comparison to those with a low secreting potential.
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