DCEP (dexamethasone, cyclophosphamide, etoposide, and cisplatin) is an effective regimen for peripheral blood stem cell collection in multiple myeloma.

DCEP (dexamethasone, cyclophosphamide, etoposide, and cisplatin) has proved to be an effective salvage therapy for refractory-relapsed MM patients. Little is known, however, about its potential as mobilizing therapy. The aim of this study was to evaluate the efficacy of DCEP in mobilizing PBSC and to define its toxicity. Fifty-five MM patients received DCEP followed by G-CSF as part of high-dose programs including autologous transplantation. At the time of mobilization, 40 patients had previously received VAD only, and 15 alkylating agents. Mobilization was successful (minimum number of CD34(+) cells 2 x 10(6)/kg) in 48/55 patients (87%), and 41/55 patients (75%) collected >4 x 10(6)/kg CD34(+) cells. Of the seven patients who did not mobilize stem cells, five (71%) had been previously exposed to alkylating agents. The median number of CD34(+) cells harvested was 5.8 x 10(6)/kg (range 2.1-22.4). There was no treatment-related mortality. The side-effects of DCEP were always tolerable. No neutropenia <1000/microl nor thrombocytopenia <50,000/microl were observed. No patient required transfusion as a consequence of therapy, or hospitalization for septic complications. In conclusion, DCEP, in addition to its demonstrated anti-tumor activity, is an effective regimen for mobilizing peripheral blood progenitor cells in myeloma patients, with little or no side-effects. These properties render DCEP a useful regimen for the debulking and mobilization phase of high-dose programs for multiple myeloma.

Rhabdomyosarcoma presenting as acute hematologic malignancy: case report and review of the literature.

The authors describe a case of undifferentiated rhabdomyosarcoma from unknown primary site, presenting as an acute hematologic malignancy with generalized lymphadenopathy, extensive bone marrow involvement and clinical and laboratory features of disseminated intravascular coagulation. Such a peculiar behaviour is known for rhabdomyosarcoma but is rare and can be a serious diagnostic problem for the clinician and the pathologist. The importance of a large spectrum immunohistochemistry as first diagnostic approach to any undifferentiated small-cell malignant tumor is stressed, together with the knowledge of the different immunoreactivity patterns. Desmin, MS-actin and myoglobin are the most reliable markers of this type of myogenic sarcoma.

Synergisms between different activation pathways in adult and aged human lymphocytes.

The present report investigates the synergistic effects of different agents (phytohaemoagglutinin (PHA), anti-CD3, phorbol-12-myristate-13-acetate (PMA) and Ionomycin on T cell activation. Results indicate that in normal lymphocytes PMA causes a dose-dependent decrease of PHA-induced blastogenesis and a marked enhancement of anti-CD3-induced 3H-thymidine uptake. There is positive synergism when cells are costimulated with PMA and the calcium ionophore Ionomycin. These data show that phorbol esters can exert either positive or negative synergisms depending on the experimental conditions. We also studied the simultaneous stimulation with PHA and anti-CD3 which gives an addictive effect for the minimal doses of the two stimuli, and an appreciable negative synergism for their highest concentrations. In order to evaluate T lymphocyte functions in the age-associated immune defect, PHA plus anti-CD3 and PMA plus Ionomycin costimulation assays were applied to a population of healthy elderly subjects. An additive effect is found after costimulation with the highest doses of PHA and anti-CD3, at variance with the negative synergism found in younger adult controls. Following costimulation with PMA plus Ionomycin, elderly subjects also display an impaired response, as compared to adult controls. No correlation was found with PHA-, anti-CD3- and PMA plus Ionomycin-induced T cell proliferation. These results underline the complexity of age-associated immune defects and suggest that alterations in different mechanisms of lymphocyte activation are responsible for the immune deficiency of aging.

Relationship between anti-cardiolipin and anti-endothelial cell antibodies in systemic lupus erythematosus.

Anti-endothelial cell antibodies (AECA) have been detected in 51 lupus sera by cell surface radioimmunoassay with a prevalence of 39.2% for IgG and 45.1% for IgM-AECA. No correlations were found between AECA and different clinical or laboratory parameters, including the presence of anti-cardiolipin antibodies and signs associated with the presence of anti-phospholipid antibodies. However, absorption with cardiolipin liposomes partially inhibited endothelial cell binding, and affinity purified anti-cardiolipin antibodies were able to react with intact human endothelial cells. The binding did not occur via Fc receptors since blocking of Fc receptors with rabbit IgG did not affect the endothelial cell reactivity. Taken together our findings support the hypothesis that antibodies directed against negatively charged phospholipids can be part of the anti-endothelial cell antibodies in certain lupus sera. The possible role of these cross-reacting antibodies in the pathogenesis of vascular thrombosis in lupus patients is discussed.

Study on the interference of ticlopidine on the immune system.

In-vitro and ex-vivo studies have been performed in order to investigate the possible interference of ticlopidine on different lymphocyte parameters. In vitro, ticlopidine displays a dose-dependent inhibition of both spontaneous and lectin-induced 3H-thymidine incorporation by normal lymphocytes. Moreover the highest drug concentrations also reduce the in-vitro PWM-stimulated Ig synthesis. Lymphocyte tests performed in healthy volunteers after a 10-day oral treatment (250 mg/day) show only a slight reduction of PHA- and ConA-induced proliferative responses and in-vitro PWM-stimulated Ig synthesis. The values found after treatment however remain within the normal range, excluding a clear interference of ticlopidine on the immune parameters tested. In addition the treatment does not affect the white blood cells nor the lymphocyte subset distribution identified by the monoclonal antibodies OKT3, OKT4 and OKT8.

Silybin inhibition of human T-lymphocyte activation.

Silybin, a 3-oxyflavone occurring in the thistle Silybum marianum, displays a dose-dependent inhibition of in-vitro lymphocyte blastogenesis induced by lectins (phytohaemagglutinin, Concanavalin A and pokeweed) and by anti-CD3 monoclonal antibody. The drug has no effect on cell viability and spontaneous 3H-thymidine incorporation, suggesting that the inhibitory activity is not due to aspecific toxicity. Since all the T-cell responses investigated require cell-membrane-associated events, the effect of silybin is probably at the level of the cell membrane, as for other flavonoids. Addition of CuSO4 prevents the inhibitory activity of silybin on PHA-induced proliferative response, indicating that the drug could exert its activity also by virtue of a chelation mechanism.

Interleukin 2 enhancement of anti-T3-induced lymphocyte activation: standardization and use of this model in immunocompromized elderly subjects.

Anti-T3-induced T cell activation was standardized in human peripheral blood lymphocytes with respect to dose response, time kinetics and effect of exogenous IL-2 on blastogenesis and on IL-2 receptor expression, identified by anti-Tac monoclonal antibody. IL-2 was able to significantly increase 3H-thymidine uptake and Tac antigen expression in unstimulated and anti-T3 activated lymphocytes. This enhancement was more evident in cultures stimulated with non-mitogenic concentrations of anti-T3, supporting the hypothesis that these concentrations sensitize T cells to the Tac-inducing effects of IL-2. This model of lymphocyte activation was then applied to selected immunocompromized elderly subjects. The aged subjects showed depressed blastogenetic responses and Tac antigen expression, which were not corrected by prolonging the time of cultures. Aged lymphocytes showed a good response to costimulation with anti-T3 and IL-2, suggesting that at least for the anti-T3 activation pathway they are able to respond to IL-2 signals.

Anti-mitochondrial type M5 and anti-cardiolipin antibodies in autoimmune disorders: studies on their association and cross-reactivity.

In a series of 42 positive sera, anti-mitochondrial type M5 antibodies (AMA-M5) were found most frequently in patients with SLE (24) and SLE-like syndromes. Patients with AMA-M5 displayed a higher prevalence of thrombocytopenia, thrombosis, biological false positive seroreactions for syphilis, lupus-like anticoagulant activity and anti-cardiolipin antibodies in comparison with a group of 43 SLE AMA-M5 negative patients. The strong association between anti-phospholipid and AMA-M5 antibodies cannot be explained entirely by cross-reactivity between these two groups of antibodies, as indicated by absorption experiments and studies using affinity purified antibody preparations. However, cardiolipin liposomes were able to reduce partially the titres of AMA-M5 sera, suggesting that a small population of AMA-M5 antibodies exists that cross-reacts with cardiolipin. The existence of this population was further substantiated by our demonstration that an IgM monoclonal antibody, from a patient with Waldenström's macroglobulinaemia, displayed both anti-cardiolipin and AMA-M5 activity, and AMA-M5 activity was completely inhibited by cardiolipin.

Antibodies to cardiac Purkinje cells: further characterization in autoimmune diseases and atrioventricular heart block.

We confirmed the occurrence of IgG antibodies reacting with ox cardiac conducting tissue in the serum of some human subjects. These antibodies failed to react with all ox cardiac conducting tissue cells; they reacted only with the cells defined as Purkinje cells. Having checked 352 sera, we found that the prevalence of antibodies to Purkinje cells was 11% in normal subjects (no correlation with sex and age), 14% in systemic lupus erythematosus, 21% in rheumatoid arthritis, 18% in progressive systemic sclerosis, and 23% in Sjögren syndrome. In 50 patients with permanent pacemakers for chronic non-postinfarction atrioventricular (AV) block the prevalence was 30% (P = 0.008). In a selected set of 29 patients with clinically idiopathic AV block located at or below the level of the His bundle the prevalence was 34.5% (P = 0.006). The possible role of anti-Purkinje cell antibodies in autoimmune damage of cardiac conduction tissue is discussed.