Bradykinin production during donor plasmapheresis procedures.

Background And Objectives: Extracorporeal circuits made of artificial substances may induce blood cells and humoral activation. Negatively charged surfaces may activate Factor XII and the prekallikrein-kinin cascade, resulting in bradykinin (BK) production. BK has been considered to be involved in severe hypotensive reactions occurring during therapeutic apheresis in patients taking angiotensin-converting enzyme (ACE) inhibitors or in those receiving platelet transfusion.

Comparison of plateletpheresis concentrates produced with Spectra LRS version 5.1 and LRS Turbo version 7.0 cell separators.

Background: The importance of transfusing WBC-reduced blood components is widely recognized, as it reduces the risk of alloimmunization and transfusion-transmitted CMV infections. The latest generation of cell separators allows the collection of WBC-reduced apheresis platelet concentrates (APCs).

Materials And Methods: Consecutive APCs (n = 232) were retrospectively evaluated: 163 collected with the Spectra LRS [leukocyte-reduction system] Version 5.

Electrolyte monitoring in patients undergoing peripheral blood stem cell collection.

In recent years peripheral blood stem cell (PBSC) collection for allogeneic or autologous transplantation has experienced an increased use in the onco-hematological setting. The latest generation cell separators allow a satisfactory and safe PBSC collection. Nevertheless, as in all therapeutic apheresis procedures, patients may experience procedure-related side-effects, mainly vasovagal reactions or symptoms related to hypocalcemia and/or hypomagnesemia.

Role of recombinant human granulocyte-macrophage colony stimulating factor for large scale collection of peripheral blood stem cells for autologous transplantation.

Twenty-seven cancer patients underwent peripheral blood stem cell apheresis during hematopoietic regeneration following induction high-dose cyclophosphamide (7 g/sqm; HD-CTX). Among these patients, eleven were also treated with granulocyte-macrophage colony stimulating factor (rhGM-CSF) for 14 days after HD-CTX. We describe technique, peripheral blood cell yields and side effects of 76 leukaphereses performed using a continuous-flow blood cell separator COBE 2997.

Large-scale collection of circulating haematopoietic progenitors in cancer patients treated with high-dose cyclophosphamide and recombinant human GM-CSF.

Circulating haematopoietic progenitors from 36 cancer patients were collected by continuous-flow leukapheresis during the phase of rapid haematopoietic recovery after pancytopenia induced by high-dose cyclophosphamide and then cryopreserved for autologous transplantation. 20 of the patients also received intravenous infusion of recombinant human granulocyte macrophage-colony stimulating factor (rhGM-CSF) for 7, 10 or 14 days after cyclophosphamide. 106 leukapheresis procedures were done for 2-5 consecutive days.

Differences between in vivo and in vitro activation of cancer patient lymphocytes by recombinant interleukin 2: possible role for lymphokine-activated killer cell infusion in the in vivo-induced activation.

In this study 15 consecutive melanoma patients were treated with two courses of bolus recombinant interleukin 2 (rIL2) and rIL2 plus in vitro-generated lymphokine-activated killers (LAK), respectively. The immunological monitoring performed after 4 days of rIL2 or rIL2 plus LAK, indicate that the in vivo peripheral blood lymphocyte (PBL), activation (spontaneous proliferation, tumor cytotoxicity, number of DR+ PBL, obtained after the second cycle of rIL2 plus LAK is significantly higher than after the first cycle of rIL2 alone. During the 5-day interval between the two courses, PBL activation returns to baseline levels and no evidence for increased sensitivity of PBL to rIL2 is present.

A phase II study of the administration of recombinant interleukin 2 (rIL-2) plus lymphokine activated killer (LAK) cells in stage IV melanoma patients.

From January 1987 to February 1988, 15 stage IV melanoma patients were treated with two courses of bolus injection of rIL-2 plus LAK cell infusions at the National Cancer Institute of Milan. The original treatment regimen included a first course of rIL-2 administration (400 micrograms/m2 bolus injection 3 times a day [TID] for 4 days) and a second course of rIL-2 administration (800 micrograms/m2 bolus injection TID for 7 days) separated by 4 consecutive daily leukaphereses. Autologous lymphokine activated killer (LAK) cells were reinfused into each patient on three occasions during the second period of rIL-2 administration.

Rapid and complete hemopoietic reconstitution following combined transplantation of autologous blood and bone marrow cells. A changing role for high dose chemo-radiotherapy?

The role of high dose chemo-radiotherapy with autologous bone marrow transplantation in the treatment of neoplasia remains to be clearly defined. Because of the iatrogenic morbidity, mortality and high cost of the supportive care required during the post-transplantation period of prolonged marrow aplasia, intensive therapy remains a sophisticated procedure lacking proper evaluation in clinical trials. We report here that when autologous bone marrow cells are supplemented with a small number of peripheral blood nucleated cells collected after prior myelosuppressive chemotherapy, complete hematological recovery is so prompt that myeloid toxicity appears no longer the major limiting factor of high-dose chemo-radiotherapy.

A new procedure for large scale production and freezing of lymphokine activated killer (LAK) cells to be used in adoptive immunotherapy of cancer.

A new procedure for activation of peripheral blood lymphocytes (PBL) with recombinant interleukin 2 (rIL2) is described. PBL obtained by leukapheresis were subjected to NH4Cl (ACK) treatment to clear erythrocyte contamination; Ficoll separation was not performed. PBL were subsequently seeded in 10-floor multitrays (Cell FactoryTM, CF), gasified and incubated at 37 degrees C for 3-4 days in a humidified 5% CO2 atmosphere.

HLA sharing in Italian recurrent abortion couples.

We performed HLA typing in 96 couples affected by recurrent abortion "sine causa". We matched these patients with 124 fertile couples and 204 individuals random paired. No significant difference in HLA sharing was demonstrated in the three study groups.

In vivo activation of lymphocytes in melanoma patients receiving escalating doses of recombinant interleukin 2.

A phase-I study of the recombinant, non-mutagenized interleukin 2 (rIL2, BioleukinTM) was performed in 12 melanoma patients (Pts). From 100 to 800 micrograms/m2 of rIL2 were administered by i.v.

Infusion of autologous alloactivated lymphocytes in melanoma patients: toxicity and immunologic monitoring.

Previous work has shown that infusion of autologous helper-enriched, alloactivated lymphocytes in melanoma patients may induce, in addition to other mild signs of toxicity, a transient but sharp elevation of blood pressure. To avoid such a disturbing symptom, the in vitro protocol of peripheral blood lymphocyte activation has been modified. In the present study we show that such a modification has led to a lower toxicity of autologous lymphocyte infusion in 4 melanoma patients; in particular, hypertension was no longer observed.

Systemic administration of autologous, alloactivated helper-enriched lymphocytes to patients with metastatic melanoma of the lung. A phase I study.

A phase I study was carried out to test the feasibility and toxicity of infusing large numbers of autologous, alloactivated helper lymphocytes into patients with metastatic melanoma. Patient peripheral blood lymphocytes (Pt-PBL) obtained by lymphopheresis and expressing the helper phenotype BT5/9 were separated and stimulated for 48 or 72 h with a pool of PBL from four to six healthy donors. Patients were then infused with such activated lymphocytes over a 2-3 h period.

Autologous cellular immune response to primary and metastatic human melanomas and its regulation by DR antigens expressed on tumor cells.

Evidence for heterogeneity of several biological features of human malignant melanoma (Me) like morphology, cytogenetics, oncogenes activation, antigenic expression, metastatizing capacity and procoagulant activity are briefly reviewed in an attempt to distinguish findings related to primary vs. metastatic lesions. In our own studies monoclonal antibodies were used to study expression of MHC class I, class II products and of Me-associated antigens (MAA) on primary and metastatic Me cells.

Granulocyte transfusion therapy.

The authors summarise their experience with the new "early granulocyte transfusion" scheme obtained in cancer patients. The data, based on three trials, clearly point out )1 the importance of early granulocyte transfusion as compared to the traditional one; 2) the efficacy of early granulocyte transfusion in pediatric age and among adult patients in those with good regenerating hemopoietic system.

Human blood cells sialidases.

The conditions of a linear assay for 4-methylumbelliferyl-alpha-D-N-acetyl-neuraminic acid (4-MU-NeuAc) sialidase activity in human lymphocytes, granulocytes, platelets and red cells plasma membranes have been determined. Lymphocytes and granulocytes have the same pH curve with two maximums at pH 4.0 and 4.

Subcellular distribution of thiamine-pyrophosphokinase and thiamine-pyrophosphatase activities in rat isolated enterocytes.

Starting from mucosal cells, isolated from rat small intestine, subcellular fractionation was carried out. Four fractions were prepared and characterized by marker enzymes and electron microscopic examination: nuclei plus microvilli, mitochondria, microsomes and supernatant. Thiamine-pyrophosphokinase activity was localized mainly in the supernatant fraction, with minor amount in mitchondria and microsomes.