E. Dispensa

Reduction of antithrombin III, protein C, and protein S levels and activated protein C resistance in polycythemia vera and essential thrombocythemia patients with thrombosis

Patients with polycythemia vera (PV) or essential thrombocythemia (ET) show a high frequency of thrombosis. The reduction of hematocrit after phlebotomy and normalization of platelet counts do not completely eliminate thrombotic risk. Some preliminary studies reported a reduction in the concentration of natural anticoagulants (NA) in this group of patients. For this reason we evaluated protein S (PS) total antigen, antithrombin III (AT III), and protein C (PC) activity in 81 patients with chronic myeloproliferative disorders (33 with PV and 48 with ET). Data were compared with those obtained in 70 healthy sex‐ and age‐matched subjects. Fifty‐seven percent of patients (46 out of 81) showed one or more thrombotic episodes at diagnosis or during follow‐up. Interestingly, we found a NA deficit in 43.5% of patients with thrombosis versus only 5.7% in the group of patients without thrombosis. These results may suggest new interpretations about the pathogenesis of thrombosis in PV or ET patients.

Prognostic value of serum IL-10 and soluble IL-2 receptor levels in aggressive non-Hodgkin's lymphoma.

Summary We investigated the prognostic significance of interleukin‐10 (IL‐10) and soluble interleuckin‐2 receptor (sIl‐2r) levles in the pretreatment serum of 105 individuals with newly‐diagnosed aggressive non‐Hodgkins lymphoma (NHL). Commercially available enzyem‐linked immunoassay kits were used for cytokine and receptor measurements. Detectable levels of IL‐10 were found in 42 (40%) patients at diagnosis, with no correlation with clinico‐haematological parameters, but in no control samples (P < 0.001).

Clinical implications of cytokine and soluble receptor measurements in patients with newly-diagnosed aggressive non-Hodgkin's lymphoma

Abstract:  Serum levels of 13 different cytokines and receptors were measured serially in 78 patients with aggressive non‐Hodgkins lymphoma (NHL) treated by 4 cycles of an intensive multi‐agent chemotherapy regimen. Recombinant human granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) was administered subcutaneously in 36 of these patients from day + 5 to day + 18 after each chemotherapy. Statistically significantly higher pretreatment levels of interleukin‐2 (IL‐2), interleukin‐6 (IL‐6), interleukin‐8 (IL‐8), interleukin‐10 (IL‐10), the soluble IL‐2 receptor (sIL‐2r), the soluble transferrin receptor (sTf‐r), and neopterin, were observed in NHL patients as compared to controls (p< 0.001 for all molecules). sIL‐2r and sTf‐r levels correlated with tumor burden (p< 0.001 and p = 0.003, respectively) whereas IL‐6 was higher in patients presenting B symptoms (p< 0.001). Cytokine levels progressively declined to normal ranges in responding patients, while they remained elevated in non‐responders. Relapsed patients also presented increased concentrations of several molecules. During the administration of GM‐CSF, we observed the drastic increase of sIL‐2r, while lower elevations were recorded for a number of cytokines, including IL‐8, tumor necrosis factor‐α, interleukin‐1β, IL‐6, and IL‐2. However, upon completion of the induction treatment, cytokine/receptor levels were comparable among individuals with the same type of response, whether or not they had received GM‐CSF. No single parameter was found to be of prognostic significance, but the combination of elevated IL‐10 and of sIL‐2r greater than 3000 U/ml selected a subgroup of 7 patients who failed induction treatment (p = 0.002). These results demonstrate that cytokine and soluble receptor measurements can provide valuable informations for a better management of NHL, in terms both of markers to monitor disease activity and of prognostic indicators.

Detection of soluble interleukin-2 receptor and interleukin-10 in the serum of patients with aggressive non-Hodgkin's lymphoma.Identification of a subset at high risk of treatment failure

Background. This study explores the ability of the combined detection of soluble IL‐2 receptor (sIL‐2r) and interleukin‐10 (IL‐10) to predict treatment failure in patients with aggressive non‐Hodgkins lymphoma (NHL) and to evaluate the modifications in cytokine measurements induced by the therapeutic administration of recombinant human granulocyte‐macrophage colony‐stimulating factor (GM‐CSF).

Recombinant α2a interferon and polycythemia vera: Clinical results and biological evaluation by means of Fourier‐transform infrared microspectroscopy

Polycythemia vera (PV) is a chronic myeloproliferative disease. The use of recombinant α2a Interferon (IFN) therapy in this disease is a novel approach. We applied Fourier‐transform infrared microspectroscopy (FT‐IR‐M) to investigate the behavior and therapeutic responsiveness of PV patients treated with IFN. A spectroscopic parameter (A1/A2) was used, corresponding to the ratio of the integrated areas of the bands at 1080 cm‐1 and at 1540 cm‐1 due to nucleic acids and proteic components, respectively, calculated on the spectra of single megakaryocytes (MKs). In previous studies, we have pointed out that MKs in PV have a surprisingly strong myeloproliferative impulse when compared to MKs from other chronic myeloproliferative diseases. Nine patients out of the 11 studied exhibited a satisfactory responsiveness to the IFN treatment. Ten patients were evaluated by the A1/A2 parameter. In 8 of these, a good agreement was seen between this parameter and the laboratory data commonly used for the assessment of this disease. The infrared parameter, which we propose, proves to be an original, reliable method for the evaluation of recombinant α2a IFN responsiveness in this disease.

Purine nucleotide metabolism in lymphocytes of B-cell chronic lymphocytic leukemia patients

Purine nucleotides were studied in human peripheral blood lymphocytes from normal subjects and patients with chronic B-cell lymphocytic leukemia (B-CLL). Nucleotide content was determined by high performance liquid chromatography (HPLC). The overall rate of purine nucleotide synthesis was measured following the incorporation of 14C-formate into the nucleotides of a lymphocytic suspension. Results indicate a substantially reduced rate of purine nucleotide metabolism.

Ecto-5’-Nucleotidase Activity in Lymphocytes from Healthy and Leukemia Patients

Purine nucleotide catabolism involves different enzymes and can be represented as follows. Open image in new window

Some aspects of purine nucleotide metabolism in lymphocytes of B-CLL.

The authors studied the behavior of some enzymes involved in purine nucleotide metabolism in human peripheral blood lymphocytes from normal and B-cell chronic lymphocytic leukemia subjects. Determinations were made with radiochemical methods associated with high performance liquid chromatography. Results indicated a marked increase in de novo purine synthesis enzymes, particularly those of the « inosinic branch point ». The latter were absent in normal lymphocytes, whereas they were well evident in leukemic lymphocytes, with the exception of AMP-S synthetase. Whereas the enzymes of the « salvage pathway » were spared in comparison to other proteins, those of the « catabolic pathway » significantly decreased. The authors discuss the possibility that such enzymes may be used as tumor markers.

Use of a functional classification of anemia in myelodysplastic syndromes to identify subgroups of patients responsive to recombinant human-erythropoietin therapy.

To the Editor: The myelodysplastic syndromes (MDS) are clonal stem cell disorders characterized by cytopenias and abnormal bone marrow maturation. In MDS patients the anemia, typically refractory to treatment, is the main feature of disease. For this reason, many authors have investigated the utility of recombinant human-erythropoietin (rh-Epo) treatment in this patient population (1, 2), and an erythroid response has been observed in about 25% of MDS patients

A Case of Acquired Idiopathic Hemophilia Successfully Treated with Immunosuppressive Drugs and Factor VIII Concentrates

The appearance of circulating factor VIII:C (FVIII:C) inhibitors in nonhemophilic patients represents a rare condition characterized by spontaneous and often life-threatening bleeding. We describe a patient with ac quired idiopathic hemophilia in whom immunosuppres sive therapy associated with human FVIII infusion deter mined a prompt and complete disappearance of the inhib itor. Given the very low number of patients with acquired hemophilia and the lack of prospective randomized clin ical trials published, we hope to contribute to a better definition of the therapeutic strategy in these patients.