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Biomedical subjects

A Pileri

Publications and source records attributed to A Pileri.

231 records · Page 13Linked to original sources
PubMedDate not supplied

Consolidation treatment with dexamethasone and alpha-2B recombinant interferon further reduces the M-component level in multiple myeloma patients responding to conventional induction chemotherapy.

Three patients with symptomatic multiple myeloma who had achieved an objective response after conventional induction chemotherapy were treated with alpha-2b-interferon plus intermittent high-dose dexamethasone as consolidation therapy. This treatment included three mega units of alpha-2b-interferon three times a week, plus 4 days pulsed high-dose dexamethasone every 28 days for 6 months. Toxicity was limited to a mild flu-like syndrome. A further and significant M-component reduction (50%), obtained after conventional chemotherapy, suggests the value of intermittent high-dose dexamethasone plus interferon as consolidation therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Multiple myeloma: altered CD4/CD8 ratio in bone marrow.

The expression of CD3, CD4 and CD8 antigens was simultaneously evaluated in peripheral blood and bone marrow lymphocytes from 22 multiple myeloma (MM) patients. The coexpression of CD11b and HLA-DR antigens was also analyzed within the CD4+ and CD8+ subpopulations in 4 MM patients. In peripheral blood the percentage of CD3+ and CD8+ cells was in the normal range, and the percentage of CD4+ was slightly reduced, leading to an altered CD4/CD8 ratio (less than 1) in only 7 patients. On the contrary, in bone marrow the percentage of CD4+ was profoundly reduced, leading to an altered CD4/CD8 ratio in all MM patients. As we previously reported in peripheral blood, an expansion of the CD11b+ and HLA-DR+ lymphocytes was observed within the CD4+ and CD8+ bone marrow T-cell subpopulations. A T-lymphocyte subset imbalance is more evident in bone marrow than in peripheral blood, and it is not due to a different lymphocyte distribution within the hematological compartments.

Antigens, CD↗
PubMedDate not supplied

Conditions influencing the expansion of the circulating hemopoietic progenitor cell compartment.

Eighteen patients (6 breast cancer, 10 non-Hodgkin's lymphoma, 2 Hodgkin's disease) were treated with high-dose cyclophosphamide (7 gr/mq), while 12 (2 breast cancer, 5 non-Hodgkin's lymphoma, 5 multiple myeloma) were additionally treated with rhGM-CSF for 14 days after cyclophosphamide. During recovery, increased peak values of circulating CFU-GM were observed in 23 out of 30 patients (13 patients after cyclophosphamide, median: 5,000 CFU-GM/ml; 10 patients after cyclophosphamide + rhGM-CSF, median: 20,150 CFU-GM/ml); five of these "high releaser patients" were in 1st relapse after MACOP-B. Seven patients showed low release of CFU-GM; they had either a history of multiple exposures to chemoradiotherapeutic treatments or bone marrow replacement by neoplastic cells or both. Four out of 23 patients with high CFU-GM release were subsequently studied after administration of high-dose etoposide (2 gr/mq): increased levels of circulating progenitors were seen again, although peak values were reduced when compared to post-cyclophosphamide period. Three patients with low release and bone marrow involvement had a clear increase of circulating CFU-GM after etoposide. The results show the influence of high-dose chemotherapy, rhGM-CSF, type of previous treatment and bone marrow involvement on the degree of circulating CFU-GM release.

Antineoplastic Agents↗
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[Human myeloma].

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B-Lymphocytes↗
PubMedDate not supplied

Biology of the human myeloma cell population. I.Macromolecular characteristics.

Several human myeloma cell populations were studied using a combination of cytochemical (Unna-Pappenheim and naphthol yellow staining, Feulgen reaction) and autoradiographical (uridine, leucine, thymidine uptake and actinomycin binding) techniques. Progressive differentiation of the myeloma population was associated with: 1. a loss of proliferative activity, 2. decreased transcriptional capacity, 3. decreased RNA and protein synthesis, 4. increased RNA and protein concentrations, 5. greater stability of the protein synthesis template. The existence of a pre-myelomatous compartment is suggested in the light of these results and those of previous kinetic studies in vivo.

Cell Cycle↗
PubMedDate not supplied

Biology of the human myeloma cell population. II. Cytokinetic characteristics.

A kinetic study of five human myeloma cell populations before and after chemotherapy using cytochemical and autoradiographical techniques showed: 1. a large number of cells, with a DNA content intermediate between 2c and 4c, that did not incorporate thymidine ('U' cells) and were indicative of ineffective myelomapoiesis; 2. non cell cycle-specific (cyclophosphamide) followed by cell cycle-specific (vincristine) treatment led to an increase in the 3H-thymidine labelling index (LI) and activation of macromolecular synthesis (increased uridine and leucine uptake and actinomycin binding capacity) pointing to early cell recruitment. A high percentage of 'U' cells can be found even after therapy. The LI variations make it clear that recruitment after therapy is overestimated by at least 40% due to ineffective myelomapoiesis. In the light of this and previous personal studies, we propose a kinetic pattern: the myeloma population may be seen as a highly differentiating population whose non-proliferating cells cannot re-enter the cycle. By contrast, the acute leukemia populations are unable to differentiate, and the non-proliferating cells (G0) can be recalled into the cell cycle.

Cell Cycle↗
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Cyclophosphamide (3.6 g/m2) therapy with G-CSF support for resistant myeloma.

BACKGROUND: In myeloma patients resistance to both melphalan- and doxorubicin-containing regimens has been related to very short survival (approximately 6 months). The development of effective regimens combined with a low toxicity rate is mandatory in this patient subgroup. METHODS: Fourteen resistant myeloma patients were treated with cyclophosphamide (a total of 3.6 g/m2 was delivered in 2 doses on days 1 and 3) and prednisone (2 mg/kg, days 1-4) every month for 4 cycles. G-CSF support was administered to reduce myelosuppression. RESULTS: This combination was well tolerated. Granulocyte levels fell below 0.1 x 10(9)/L in all patients after a median of 9 days (range 8-11), followed by recovery to 0.5 x 10(9)/L after a median of 12 days from the start of treatment (range 10-13 days). Platelets never fell below 50 x 10(9)/L. All patients were treated on an outpatient basis and only 2 required hospitalization for major complications (pneumonia and heart failure). Response to cyclophosphamide was observed in 6/14 patients: 2 achieved complete remission, 4 showed a 50% or greater reduction of the M-component. Five patients are still in remission after 2, 6, 7, 9 and 10 months; 1 relapsed after 10 months. All patients except one are alive 4-16 months from the start of treatment. CONCLUSIONS: This schedule may represent a new approach for resistant myeloma, and its very low toxicity allows it to be delivered on an outpatient basis.

Aged↗
PubMedDate not supplied

Reduction of plasma fibrinolytic activity following high-dose cyclophosphamide is neutralized in vivo by GM-CSF administration.

BACKGROUND: GM-CSF has broad clinical applicability as a potent myelopoietic stimulator. However, its function is not restricted to the myelopoietic system and several observations suggest that GM-CSF may interfere with the hemostatic balance. In order to assess whether GM-CSF has any influence on hemostasis, we evaluated some coagulative and fibrinolytic parameters in patients treated with GM-CSF following chemotherapy. METHODS: Fibrinolytic activity (FA), fibrinogen and D-dimer were evaluated before and after high-dose cyclophosphamide in 6 patients additionally treated with GM-CSF and in 5 control patients; moreover, tissue plasminogen activator (tPA) was assayed in those treated with GM-CSF. Comparative in vitro analysis was performed on cultured endothelial cells before and after exposure to GM-CSF. RESULTS: Control patients showed a significant decrease in plasma FA after chemotherapy compared to basal values (FA/mm2: 15.6 +/- 2.1 at day + 2 and 20.8 +/- 19 at day + 4 vs. 103.8 +/- 64.2 at day 0; p < 0.005); conversely, no FA reduction was observed in GM-CSF-treated subjects. In this latter group a marked increase in tPA antigen was seen, consistent with enhanced FA. No significant changes in plasma D-dimer and fibrinogen values were detected in the two groups. tPA, urokinase-type plasminogen activator, PAI-1 and procoagulant activity were evaluated in vitro on cultured human endothelial cells and found to be unchanged following GM-CSF addition. CONCLUSIONS: The results demonstrate that high-dose chemotherapy may negatively influence plasma FA. This adverse side effect is neutralized by GM-CSF administration. The discrepancy found between in vitro and in vivo GM-CSF activity on hemostatic may be explained by in vivo GM-CSF stimulation of cell types other than endothelial cells.

Adult↗
PubMedDate not supplied

Long-term molecular remission after conventional chemotherapy in a patient with Philadelphia-negative acute lymphoblastic leukemia.

Adult Philadelphia (Ph1) negative acute lymphoblastic leukemia (ALL) is usually treated with conventional chemotherapy regimens. Long-term disease-free survival is often achieved. The rearrangement of immunoglobulin heavy-chain genes has been used to evaluate minimal residual disease. A novel nested-polymerase chain reaction (PCR) approach was used here to study a patient in long-term complete remission (CR) after the BFM regimen. No evidence of tumor cell contamination was found in bone marrow cells collected after 93 months of CR. This finding supports the hypothesis that conventional chemotherapy can induce long-term molecular remission and cure in Ph1 negative ALL.

Acute Disease↗
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Results of a low aggressivity chemotherapy regimen (CVP/CEB) in elderly Hodgkin's disease patients.

BACKGROUND: Hodgkin's disease (HD) after the age of 65 years is uncommon and there are no published data on chemotherapy regimens devised for elderly HD patients. PATIENTS AND METHODS: From 1990 to 1993, 25 elderly HD patients were treated with the CVP/CEB regimen: chlorambucil 6 mg/sqm p.o. days 1 through 7, vinblastine 6 mg/sqm i.v. on day 1, procarbazine 100 mg/sqm p.o. days 1 through 7, prednisone 30 mg/sqm p.o. days 1 through 7, cyclophosphamide 500 mg./sqm i.v. day 15, etoposide 70 mg/sqm i.v. day 15, bleomycin 10 mg/sqm i.v. day 15. Each course was repeated every 4 weeks. Stage I and II patients were treated with 3 courses followed by involved field radiotherapy, while more advanced stage patients received 6 courses and radiotherapy was limited to bulky areas. The results of the CVP/CEB regimen are retrospectively compared to those of 74 elderly patients treated between 1982 and 1989 and subdivided into the following 2 groups: 32 patients treated according to the same therapy used at that time in younger patients, and 42 patients given alternative low aggressivity or palliative treatment. RESULTS: CVP/CEB is a well-tolerated regimen, with only 1 (4%) toxic death and 2 (8%) protocol violations/interruptions. The CVP/CEB complete remission rate (73%) compares favorably with our previous groups of patients, mainly because of the lower toxic death rate. However, the CVP/CEB relapse-free survival rate is lower than that of patients treated with more aggressive conventional regimens (47% vs. 77%, p < 0.02). The CVP/CEB overall survival and event-free survival rates are 55% and 32%, respectively, and they are not statistically different from those of patients treated before 1990. CONCLUSIONS: CVP/CEB is a well-tolerated low toxicity regimen with a high CR rate. The relapse rate is high and event-free survival is comparable to that of patients treated conventionally. Our results suggest the need for individualized treatment criteria for older patients with HD.

Aged↗
PubMedDate not supplied

Lupus anticoagulant and thrombosis: role of von Willebrand factor multimeric forms.

OBJECTIVE: Patients with lupus anticoagulant (LA) have an increased incidence of venous and arterial thrombosis whose pathogenesis is still unclear. High molecular weight von Willebrand Factor (vWF) multimers seem to play a causal role in shear stress-induced platelet aggregation and thrombus formation. We studied whether in patients with LA, alterations in the vWF multimers might coexist. METHODS: The multimeric composition of plasma vWF was analysed by SDS-electrophoresis and immunoblotting in 43 subjects positive for LA. About 2/3 of the patients had had either ischemic stroke, recurrent abortions, deep vein thrombosis (DVT) or a combination of these; the remaining subjects had never had any thrombotic events. RESULTS: An abnormal vWf multimeric pattern was found in 16 patients (37.2%); no correlation was found with the diagnosis, but the presence of abnormal vWF significantly correlated with the site of the thrombosis: indeed, it was never detected in subjects with DVT, but was found in 71.4% of patients with multiple abortions, in 50% of those with stroke and even in 25% of non-thrombotic patients. CONCLUSION: The hypothesis is put forward that abnormal VWF may represent an additional risk factor to LA for arterial thrombosis.

Abortion, Habitual↗
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Natural and acquired inhibitors of hemostasis in selected symptomatic outpatients with venous thromboembolic disease.

BACKGROUND AND OBJECTIVE: Deficiencies of natural inhibitors and the presence of lupus anticoagulant are important risk factors leading to venous thromboembolic events. Before resistance to activated protein C (APC-R) was identified, the overall prevalence of inherited abnormalities of hemostasis in non-selected outpatients with venous thromboembolic disease was under 10%. This cast doubts on the of cost effectiveness and clinical significance of assaying hemostasis inhibitors in all such patients. The goal of this study is to evaluate the prevalence of inherited and acquired abnormalities of hemostasis in younger symptomatic outpatients with objectively diagnosed venous thromboembolic disease (VTD). METHODS: From October 1994 to October 1996, we diagnosed, treated and followed 191 consecutive outpatients with an objective diagnosis of venous thromboembolic disease, and assayed natural and acquired hemostasis inhibitors in 81 of them aged less than 50; in addition, 129 relatives of patients with inherited deficiencies were evaluated. RESULTS: Twenty-six of the patients under age 50 showed inherited deficiencies of natural inhibitors (3 antithrombin, 5 protein C, 3 protein 5 and 14 APC-R, 1 dysfibrinogenemia) and 8 patients had lupus anticoagulant (LA): abnormalities of hemostasis were found in 41.9% (95% confidence interval 31.1-53.5). In older selected patients, 60% (95% confidence interval 40.6-77.3) of the subjects showed abnormalities. Seventy-two of the relatives displayed natural inhibitor deficiencies; 88.5% of the families studied had at least one relative with the same defect as the propositus. INTERPRETATION AND CONCLUSIONS: A simple selection based on age, clinical and family history shows the existence of a high prevalence and the important clinical significance of abnormalities of hemostasis in symptomatic outpatients with venous thromboembolic disease.

Adult↗