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M Vittori

Publications and source records attributed to M Vittori.

16 recordsLinked to original sources

Large volume leukapheresis for collecting hemopoietic progenitors: role of CD 34+ precount in predicting successful collection.

In this work we evaluated the efficacy of stem cell collection with Large Volume Procedures. (LVP), and analysed the importance of the CD34+ cell precount in promoting the collection of a sufficient number of CD34+ cells for transplantation, using the Univariate Logistic Regression analysis. Eighty-nine leukapheresis were performed in 49 patients with hematological malignancies and solid tumors, mobilized with chemotherapy plus Granulocyte Colony Stimulating Factor (G-CSF). For each procedure 15.8 liters of blood were processed. The median value of Nucleated Cells (NC) and CD34+ cells precount was respectively 8.29 x 10(9)/ml (range 1.13/45.4) and 43.08 x 103/ml (range 1.06/795.2). Results show the capability of LVP to collect large quantities of hemopoietic progenitors with a median CD34+ cell total yield of 215.02 x 10(6) (range 5.03/2210). The yields per patients' body weight were: CD34+ cells 3.23 x 10(6)/kg (range 0.081/41.58). The regression analysis between blood cell precounts and collection yields gave the following correlations: the CD34+ cell precount correlates with CD34+ yield (r = 0.78 p < 0.00) and with CD34+ cell yield/kg (r = 0.76 p < 0.00). The number of CD34+ cells processed correlated with the number of CD34+ cells collected/kg (r = 0.83 p < 0.000). To investigate the importance of CD 34+ cell precount in promoting CD34+ cell yields > or =2.5 x 10(6)/kg we performed a Univariate Logistic Regression analysis that showed in our patients a probability of collecting > or =2.5 x 10(6) CD34+/kg that rose from 0.6 to 0.95 for CD 34+ precounts that oscillated from 30 to 40 x 10(3) CD34+ cells/ml, respectively. The Univariate Logistic Regression gave a probability of collecting > or =2.5 x 10(6) CD34+ cells/kg that oscillated between 0.64/0.98 for values of CD34+ cells processed from 6 x 10(6)/kg to 8 x 10(6)/kg, p < 0.000. Sixty-three percent of patients reached the target dose of 2.5 x 10(6) CD34+ cells/kg with only one LVP. Until now 12 patients have been transplanted and all have had a prompt and complete lasting recovery. These results confirm the efficacy of LVP in harvesting hemopoietic progenitors and their ability in reconstituting hemopoiesis of transplanted patients, enabling the estimation of CD34+ precounts and CD34+ cells processed values, highly predictive for the collection of > or =2.5 x 10(6) CD34+ cells/kg. Furthermore, the Logistic Model suggests that the best strategy to plan a successful CD34+ cell collection procedure is to identify for each patient the amount of CD34+ cells/kg to be processed rather than the fixed processing of 3/5 blood volumes in all patients.

Adolescent↗

Evaluation of a new protocol for peripheral blood stem cell collection with the Fresenius AS 104 cell separator.

In this report we analyzed sixty leukapheresis procedures on 35 patients with a new protocol for the Fresenius AS 104. Yields and efficiencies for MNC, CD 34+ cells, and CFU-GM indicate that the new protocol is able to collect large quantities of hemopoietic progenitors. Procedures were performed processing 8.69 +/- 2.8 liters of whole blood per apheresis and modifying 3 parameters: spillover-volume 7 ml, buffy-coat volume 11.5 ml, centrifuge speed 1,500 rpm; blood flow rate was 50 ml/min and the anticoagulant ratio was 1:12. No side effects were observed during apheresis procedures except for transient paresthesia episodes promptly resolved with the administration of calcium gluconate. Yields show a high capacity of the new program to collect on average MNC 17.28 +/- 10.85 x 10(9), CD 34+ 471 +/- 553.5 x 10(6) and CFU-GM 1278.7 +/- 1346.3 x 10(4) per procedure. Separator collection efficiency on average was 49.91 +/- 23.28% for MNC, 55.1 +/- 35.66% for CFU-GM, and 62.97 +/- 23.09% for CD 34+ cells. Particularly interesting are results for MNC yields and CD 34+ efficiency; these results make the new program advantageous or similar to the most progressive blood cell separators and capable to collect a sufficient number of progenitor cells for a graft with a mean of 1.80 +/- 0.98 procedures per patient.

Adolescent↗

The assessment of biomarkers to detect nephrotoxicity using an integrated database.

Groups of industrial workers exposed to heavy metals (cadmium, mercury, and lead) or solvents were studied together with corresponding control groups. The cohorts were collected from several European centers (countries). Eighty-one measurements were carried out on urine, blood, and serum samples and the results of these analyses together with questionnaire information on each individual were entered into a central database using the relational database package Rbase. After the completion of the database construction phase, the data were exported in a format suitable for analysis by the statistical package SAS. The potential value of each test as an indicator of nephrotoxicity was then assessed. Rigorous exclusion criteria were applied which resulted in the elimination of some tests and samples from the dataset. The measurable contributions of smoking, gender, metal exposure, and site were either singly or in combination assessed by biomarkers for nephrotoxicity. The parameters measured included three urinary enzymes, six specific proteins, total protein, two extracellular matrix markers, four prostaglandins and anti-GBM antibodies, and beta 2-microglobulin in serum. The most sensitive renal tests included the urinary enzymes N-acetyl-beta-D-glucosaminidase (NAG) and intestinal alkaline phosphatase (IAP), brush border antigens, and urinary low-molecular-weight proteins. Of the newer tests investigated the prostaglandins were the most promising. Different patterns of biomarker excretion were observed following exposure to lead, cadmium, or mercury. The dataset provides a unique repository of data which could provide the basis of an enlarging source of information on normal human reference ranges and on the effects of exposure to toxins and the use of biomarkers for monitoring nephrotoxicity.

Biomarkers↗

High-dose carboplatin, etoposide and melphalan (CEM) with peripheral blood progenitor cell support as late intensification for high-risk cancer: non-haematological, haematological toxicities and role of growth factor administration.

The present report describes the non-haematological toxicity and the influence of growth factor administration on haematological toxicity and haematopoietic recovery observed after high-dose carboplatin (1200 mg m(-2)), etoposide (900 mg m(-2)) and melphalan (100 mg m(-2)) (CEM) followed by peripheral blood progenitor cell transplantation (PBPCT) in 40 patients with high-risk cancer during their first-line treatment. PBPCs were collected during the previous outpatient induction chemotherapy programme by leukaphereses. CEM administration with PBPCT was associated with low non-haematological toxicity and the only significant toxicity consisted of a reversible grade III/IV increase in liver enzymes in 32% of the patients. Haematopoietic recovery was very fast in all patients and the administration of granulocyte colony-stimulating factor (G-CSF) plus erythropoietin (EPO) or granulocyte-macrophage colony-stimulating factor (GM-CSF) plus EPO after PBPCT significantly reduced haematological toxicity, abrogated antibiotic administration during neutropenia and significantly reduced hospital stay and patient's hospital charge compared with patients treated with PBPCT only. None of the patients died early of CEM plus PBPCT-related complications. Low non-haematological toxicity and accelerated haematopoietic recovery renders CEM with PBPC/growth factor support an acceptable therapeutic approach in an adjuvant or neoadjuvant setting.

Adult↗

Evaluation of two different protocols for peripheral blood stem cell collection with the Fresenius AS 104 blood cell separator.

OBJECTIVES: Reconstitution of hematopoiesis by means of peripheral blood stem cells is a valid alternative to autologous bone marrow transplantation. The aim of this investigation was to increase the efficiency of collection of circulating blood progenitor cells and to obtain a purer product for transplant. METHODS: We carried out leukapheresis procedures with the Fresenius AS 104 blood cell separator, using two different protocols, the previously used PBSC-LYM and a new mononuclear cell collection program. RESULTS: Both programs were highly effective in collecting mononuclear cells (MNC) and CD34+ cells. Some differences were found, especially regarding MNC yield and efficiencies. There are remarkable differences in the efficiency of collection of CD34+ cells (62.38% with the new program as opposed to 31.69% with the older one). Linear regression analysis showed a negative correlation between blood volume processed and MNC efficiency only for the PBSC-LYM program. Differences were also observed in the degree of inverse correlation existing in both programs between patients' white blood cell precount and MNC collection efficiency. The inverse correlation was stronger for the PBSC-LYM program. Seven patients with solid tumors and hematologic malignancies received high dose chemotherapy and were subsequently transplanted with peripheral blood stem cells collected using the new protocol. All patients obtained a complete and stable engraftment with the reinfusion product collected with one or two leukapheresis procedures. CONCLUSIONS: High efficiencies and yields were observed in the new protocol for MNC and CD34+ cells. These were able to effect rapid and complete bone marrow recovery after myeloablative chemotherapy.

Adolescent↗

The combination of erythropoietin and granulocyte colony-stimulating factor increases the rate of haemopoietic recovery with clinical benefit after peripheral blood progenitor cell transplantation.

In order to investigate the effects of erythropoietin (EPO) plus granulocyte colony-stimulating factor (G-CSF) administration after peripheral blood progenitor cell transplantation (PBPCT) we performed a phase I/II study in patients with high-risk cancer. 15 consecutive patients were treated wit recombinant human G-CSF (rhG-CSF) at the dose of 5 micrograms/kg subcutaneously (s.c.) every 24 h until day + 12 and with recombinant human EPO (rhEPO) at the dose of 150 IU/kg s.c. every 48 h until day + 11 following PBPCT. Their haemopoietic recovery was compared to that obtained in eight historic and control patients who did not receive any cytokines after PBPCT. No side-effects were observed during EPO plus G-CSF treatment and the treatment was not discontinued in any of the patients before completion of the treatment plan. The administration of EPO plus G-CSF after PBPCT produced a significant increase in the rate of white blood cell (WBC) (P = 0.0005), polymorphonuclear leucocyte (PMN) (P = 0.0005) and platelet (PLT) (P = 0.0105) recovery compared to the control group. The acceleration in haemopoietic recovery observed in the EPO plus G-CSF-treated patients produced a significant reduction of the days with WBC < 1 x 10(9)/l (P = 0.0009), PMN < 0.2 x 10(9)/l (P = 0.0030) and PMN < 0.5 x 10(9)/l (P = 0.0006). EPO plus G-CSF-treated patients required a significantly lower number of single donor PLT transfusions (P = 0.0142) and did not experience neutropenic fever, but historic control patients experienced fever > 38 degrees C for a median period of 4 d (0-12) with a medial period of parenteral antibiotic administration of 7.5 d (0-17). The length of the hospital stay was significantly shorter in the study group than in the historic control group (P = 0.0264). In conclusion, we can confirm that EPO plus G-CSF treatment is feasible and potentiates the haemopoietic recovery after PBPCT, thus simplifying the clinical management of cancer patients who undergo high-dose chemotherapy.

Adult↗

Evaluation of a novel automated protocol for the collection of peripheral blood stem cells mobilized with chemotherapy or chemotherapy plus G-CSF using the Fresenius AS104 cell separator.

Forty-seven peripheral blood stem cell (PBSC) collections were carried out on patients mobilized with chemotherapy and 63 on patients mobilized with chemotherapy plus G-CSF (Filgrastim), using the Fresenius AS104 cell separator and a novel automated PBSC collection protocol. As expected, cell yields were significantly higher in the series mobilized using chemotherapy plus G-CSF. The low platelet and red blood cell contamination permitted freezing of the apheresis product without further manipulation, other than plasma removal in both series. In patients mobilized with chemotherapy we obtained a MNC and a hemopoietic progenitor (CFU-GM, BFU-e, and CD34+ cells) collection efficiency comparable or superior to those reported by Bender (1992) with the Baxter CS3000 Plus after mobilization with cyclophosphamide. A significant decrease in MNC, BFU-e, and CD34+ cell collection efficiency was found in patients mobilized with chemotherapy plus G-CSF compared to those obtained in patients mobilized with chemotherapy alone. Ten patients achieved a prompt and stable engraftment after high dose chemotherapy and the infusion of cryopreserved PBSC collected using this protocol. Studies are in progress in order to improve MNC and hemopoietic progenitor collection efficiency in patients mobilized with G-CSF to obtain a graft in no more than one or two procedures.

Adolescent↗

Five-year experience in PBSC collection: results of the Catholic University of Rome.

Several authors have reported a faster immunological and hemopoietic post-transplant reconstitution using autologous peripheral blood stem cell (PBSC) than using autologous bone marrow stem cells. A large number of PBSC can be collected by leukapheresis during the hematological recovery after induction or salvage chemotherapy. In our experience we demonstrated that several separators, even if they have different results in mononuclear cell (MNC) yields, red blood cell and platelet contaminations, are able to collect PBSC for autotransplantation in patients with several malignant diseases and different status of disease. Eighty three patients were submitted to 590 leukapheresis procedures using 4 different blood cell separators: the results showed that all employed protocols are efficient in the collection of peripheral MNC even if after the widespread use of granulocytecolony stimulating factor (G-CSF) in the harvesting phase, the blood cell separator efficiency in terms of MNC is reduced. The use of GCSF in combination with other growth factors, during chemotherapy mobilization could simplify, in the future, this therapeutical program even if improvements in the efficiency of PBSC collection protocols are required.

Adolescent↗

Autologous blood stem cell harvesting and transplantation in patients with advanced ovarian cancer.

We investigated the feasibility of a programme of autologous blood stem cell (ABSC) harvesting and transplantation in 13 patients with advanced ovarian cancer, previously untreated by chemotherapy or radiotherapy and entering a phase II study of high-dose cisplatin, etoposide and carboplatin with haematopoietic stem cell rescue. Prior to high-dose treatment all patients underwent two courses of cisplatin and cyclophosphamide. An 8-fold increase of the peripheral colony forming unit granulocytic-macrophage (CFU-GM) was observed during recovery from myelosuppression after the first chemotherapy course. The second course determined a 2.5-fold increase of peripheral CFU-GM. In 70% of enrolled patients (nine patients) we were able to perform ABSC harvesting by leukaphereses; in the apheresed patients we harvested an average of 20.8 x 10(4)/kg CFU-GM (range 10.9-37.0). Haematopoietic trilineage engraftment, established as the number of days necessary to reach white blood cells (WBC) greater than 1.0 x 10(9)/l, polymorphonuclear leucocytes (PMN) greater than 0.5 x 10(9)/l and platelets (PLT) greater than 50 x 10(9)/l, occurred very promptly and was sustained in the same series after high-dose cisplatin, carboplatin and etoposide, followed by autologous blood stem cell transplantation (ABSCT). In our experience we found a significant correlation (r = 0.77; P less than 0.05) between CFU-GM infused dose and the engraftment speed of PMN. We conclude that the combination of cisplatin and cyclophosphamide is effective in mobilizing haematopoietic progenitors in the peripheral blood of patients with advanced ovarian cancer, previously untreated by chemoradiotherapy. Moreover, ABSCT is capable of rapidly restoring the haematopoietic function after high-dose treatment and for this reason it represents a particularly advisable therapeutic option for the treatment of solid tumours because these patients are commonly older than 50 and can be excluded from bone marrow transplantation.

Adult↗

Comparison of the side effects of therapeutic cytapheresis and those of other types of hemapheresis.

The side effects of a series of 2418 hemapheresis procedures performed in a total of 570 subjects (patients and donors) are described. Patients with various diseases were subjected to plasmapheresis (926 procedures in 181 patients) or cytapheresis (305 procedures in 89 patients). One hundred twelve plasmapheresis procedures and 1075 of cytaphereses were also performed in 300 blood donors. A total of 225 complications involving 107 patients (39.6%) occurred during 196 (15.9%) therapeutic procedures. Among the blood donors only 45 complications, involving 35 patients (11.6%) occurred during 45 procedures (4.2%). The complications seen with therapeutic plasmaphereses were circulatory disturbances (38% of all those observed), citrate reactions (27%), technical problems (20%), allergic reactions (9%) and miscellaneous complications (6%). Therapeutic cytaphereses were complicated by citrate reactions (44%), technical problems (25%), circulatory disturbances (14%), allergic reactions (11%) and miscellaneous complications (6%). Complications in the blood donor group included circulatory disturbances (51%), technical problems (36%) and various other problems (13%). No infectious complications or deaths were observed. The probability that adverse reactions will occur depends on the condition of the patient, the frequency of the sessions and the volume of fluid exchanged. Evaluation of the main risk factors, use of less intensive protocols and interruption of the session at the first sign of disturbances will help improve patient tolerance of these procedures.

Blood Donors↗

Semiautomated autologous bone marrow processing for transplantation.

This paper describes the development of a semiautomated procedure for autologous bone marrow processing, prior to ex vivo manipulation and/or cryopreservation. This procedure was employed with a pediatric bowl (125 ml Latham bowl) and the automated DuPont Stericell processor. We have obtained a mononuclear cell recovery of 85% and a hemopoietic progenitor cell recovery of 81% (CFU-GM; BFU-E), with a red cell removal of 84%. We believe that a reliable and standardized bone marrow processing procedure is the basic necessity for a bone marrow transplantation program.

Automation↗

Rationale for large scale bone marrow hemopoietic stem cell manipulation.

Many years have passed since the first attempt in marrow grafting was performed (1939). During this period several techniques have been developed in marrow processing and manipulation to overcome bone marrow transplant complications: the ABO barrier in case of major incompatibility between donor and recipient, the graft-versus-host disease due to the presence of allogeneic mature T-lymphocytes in cellular suspension and the neoplastic cell residue in autografts. At the end, the final volume of autologous mononuclear cell suspension must be frozen and an optimized cryopreservation allows a cell viability and subsequently an adequate medullar repopulating capacity.

Blood Group Incompatibility↗

High dose chemotherapy with cisplatin, VP16 and carboplatin with stem cell support in patients with advanced ovarian cancer.

Authors treated 4 patients suffering from advanced ovarian cancer with high-dose chemotherapy and autologous peripheral blood stem cell (APBSC) or autologous bone marrow stem cell (ABM) as hematopoietic support. In three patients were collected peripheral blood stem cells using a fully automated blood cell separator during hematopoietic recovery following aplasia induced by non-intensive chemotherapy (cisplatin 200 mg/m2 and cyclophosphamide 1,500 mg/m2). Hemopoietic reconstitution of the four patients submitted to APBSC or ABM support after high-dose chemotherapy (cisplatin 100 mg/m2, VP16 650 mg/m2 and carboplatin 1,800 mg/m2) showed the low hematological toxicity of our treatment with APBSC support. Moreover, the drug combination of cisplatin and cyclophosphamide has clinical activity in ovarian cancer and it is an optimal association to mobilize and harvest large number of PBSC.

Adult↗

A comparison between two different procedures for bone marrow processing: a semiautomated procedure vs manual starch sedimentation.

After high-dose chemotherapy, autologous cryopreserved bone marrow infusion is employed to restore rapidly the compromised hematopoietic function. An efficient bone marrow processing reduces the infusion toxicity produced by hemolized red cells, granulocytes and platelets clumping and DMSO amount; moreover it increases freezing efficacy, a critical step in autologous bone marrow grafting techniques. Gravity sedimentation technique with 6% hydroxyethyl-starch (HES) or a semiautomated procedure using a blood cell processor were used in our center to manipulate ex-vivo the collected bone marrow. In our experience we compared these two different procedure and we evaluated their efficiency.

Antineoplastic Combined Chemotherapy Protocols↗

A preliminary survey of Italian experience on bone marrow harvesting, processing and manipulation. The Italian Cooperative Study Group on Cell Manipulation in Hematology.

The following report describes the initial stage of the activity of the Italian Cooperative Study group on cellular manipulation in hematology consisting of a retrospective evaluation of data regarding bone marrow (BM) harvesting processing, and proceedings from 20 Italian Centers. Two thousand, three hundred and eighty-four BM have considered: 1073 were performed for autografts and 1311 for allografts. A cohort of adverse effects in marrow harvesting were reported by 7 Centers out of 20, including one death caused by tracheomalacia during the anesthesia. Twelve Centers used blood separators as a mean for marrow processing. Eight Centers used the RBC removal technique in major donor/recipient AB0 incompatibility. Ficol-Hipaque gradient was employed in 7 Centers. T-depletion were accomplished with monoclonal antibodies in 7 Centers and elutriation in two Centers. Fifteen Centers provided to purge the residual tumour cells with chemicals (11), immunological (4) and chemo-physical means (1).

Bone Marrow Transplantation↗