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Biomedical subjects

L Pierelli

Publications and source records attributed to L Pierelli.

At least 91 records · Page 5Linked to original sources
PubMed1991

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↗
PubMed1991

Antiproliferative activity of quercetin on normal bone marrow and leukaemic progenitors.

We used an in vitro clonogenic assay in semi-solid medium to test the sensitivity of normal bone marrow and acute myeloid and lymphoid leukaemia progenitors to the flavonol quercetin. We have studied 14 acute myeloid (AML) and four acute lymphoid (ALL) leukaemias. All ALL and the vast majority of AML (12/14) had a high sensitivity to quercetin with more than 50% growth inhibition at 2 x 10(-6) M quercetin. One M3-AML was partially quercetin-sensitive displaying 60% surviving AML-colony forming units (CFU-AML) at a quercetin concentration of 10(-5) M. One M1-AML was resistant to the growth inhibitory effect of quercetin at a concentration of 2 x 10(-5) M. The clonogenic efficiency of both AML and ALL positively correlated with leukaemic colony-forming unit (CFU-L) sensitivity to quercetin suggesting that this parameter can be useful in predicting quercetin responsiveness of leukaemic cells. We have also studied the effect of various quercetin concentrations on colony formation by normal bone marrow cells. At a quercetin concentration of 10(-5) M, we observed (in five different experiments) a mean recovery of 53% and 65% of erythroid blast-forming units (BFU-E) and granulocyte-macrophage colony-forming units (CFU-GM), respectively. Thus, normal bone marrow appeared partially resistant to quercetin, being inhibited less than 50% by quercetin concentration higher than 2 x 10(-5). When normal bone marrow were deprived in CD34+ haematopoietic progenitors the resultant population became highly sensitive to quercetin, with a mean recovery of BFU-E and CFU-GM of 5% and 12% of controls respectively in the presence of 2 x 10(-5) M quercetin. Furthermore, CD34 progenitors, positively selected, appeared fully resistant to quercetin concentrations as high as 2 x 10(-5) M. Thus, CD34+ progenitors are a quercetin-resistant component in normal bone marrow. In conclusion, our results further provide a biological basis for the therapeutic use of quercetin, considering that this compound could inhibit leukaemic cell growth without suppressing normal haematopoiesis.

Acute Disease↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

Autologous peripheral blood stem cell transplantation in malignancies involving bone marrow.

Six patients suffering from refractory malignancies (3 NHL, 1 MM, 1 AML, 1 neuroblastoma) received high dose of chemotherapy and autologous peripheral blood stem cell transplantation (APBSCT). The recruitment of PBSC was performed using conventional salvatage schedules of therapy. The patients received a median of 8.69 MNC/kg bw and 20.87 CFU-GM x 10(4)/kg bw. Prompt engraftment occurred in all patients and the median number of days to achieve WBC greater than 1 x 10(9)/l was 16.5 (range 7-26), PMN greater than 0.5 x 10(9)/l was 21.5 (range 6-37) and PLTs greater than 50 x 10(9)/l was 17.5 (range 4-31). Four patients achieved a complete remission. One patient (neuroblastoma) died of progressive disease after a partial response. One patient died in relapse because of drug related toxicity.

Adolescent↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

Autologous bone marrow processing for autotransplantation using an automated cell processor and a semiautomated procedure.

Twenty bone marrow aspirates harvested for autotransplantation from 20 patients suffering from several oncohematological diseases were processed using the automated Du Pont SteriCell processor. In 15 bone marrow harvests, the interface buffy coat cells were collected using the SteriCell processor in manual mode with a semiautomated procedure. The procedure yielded an average red cell removal of 84% and an average mononuclear cell (MNC) recovery of 86%. Cloning efficiencies of hematopoietic progenitor cells (CFU-GM and BFU-e) did not differ between processed and recovered MNCs. Four cryopreserved bone marrow buffy coats were thawed and reinfused into four patients who had undergone high dose chemotherapy. Stable engraftment was observed in all cases. In five bone marrow harvests, the SteriCell automated density gradient MNC isolation procedure was performed after buffy coat collection. The whole two-step procedure allowed an average MNC recovery of 69%. CFU-GM and BFU-e assays did not show a significant difference in cloning efficiency between processed and recovered bone marrow MNCs. We conclude that the SteriCell processor offers rapid, safe and feasible procedures for the semiautomated processing of human bone marrow for transplantation. The clinical efficacy of density gradient separated bone marrow employing the automated step and the opportunity to use fully automated processing must be investigated.

Adult↗
PubMed1990

Effects of natural beta-interferon and recombinant alpha-2B-interferon on proliferation, glucocorticoid receptor content, and antigen expression in cultured HL-60 cells.

In the current study, we investigated the effects of natural beta-interferon (beta-IFN) and recombinant alpha-2b-interferon (alpha-IFN) on the growth of the HL-60 cell line. Cells cultured in a medium that contains various concentrations (from 10 to 1000 IU/ml) of interferons showed a growth inhibition, which reaches the maximum after a 6-day treatment, at the highest dose used. Furthermore, we studied the effect of both beta-IFN and alpha-IFN on the level of glucocorticoid receptors. This was enhanced more than 30% with respect to control in HL-60 cells exposed for 24 hours to concentrations of beta-IFN that ranged from 100 to 1000 IU/ml. The increase of the receptor amount was seen even if cells were treated for 5 days, and was not accompanied by a modification of antigen expression of HL-60 cells. alpha-IFN did not modify the glucocorticoid receptor level substantially in our experimental conditions. Our data indicate that both beta-IFN and alpha-IFN regulate HL-60 cell proliferation. Additional studies are required to clarify if modifications of the receptor level induced by beta-IFN could be related to the modulation of hormone-sensitivity in this model.

Antigens↗
PubMedDate not supplied

Fetal tissue collection from spontaneous abortions: a report from a single centre.

Due to immunological immaturity, the fetus is the ideal recipient as well as donor of haemopoietic stem cells (HSCs); thus intrauterine therapy may prove to be effective in all major haemopoietic disorders when early prenatal diagnosis is available. In man, "fetus-to-fetus" transplantation has demonstrated the possibility of grafting donor HSCs and reconstituting immunodeficient fetuses. The limitations of fetal tissue use for transplantation derive from the origin of tissues from elective abortions. Early and late live spontaneous abortions may constitute an alternative to elective abortions, but are widely considered as unsuitable for fetal tissue collection because of rapid loss of viability and/or infections. The aim of this retrospective study was to assess the number of live abortions in a population of women who underwent spontaneous abortion in a single centre. In a 19-month period, 9 spontaneous abortions alive at the moment of delivery and 8 with a heart beat at the last ultrasound scan before abortion were recorded. In 1 case, fetal liver (FL) harvesting was easily performed and the tissue was cryopreserved, subsequently thawed and injected into a monkey fetus. This case shows the feasibility of this approach. The majority of cases reviewed consisted of late abortions. These findings clearly show that fetal tissue collection from spontaneous abortions is feasible for research purposes, for postnatal FL transplantation and for intrauterine transplantation, postnatal FL transplantation and for intrauterine transplantation, provided that depletion of more mature cells is performed when FL of later gestational age are used.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Spontaneous↗
PubMedDate not supplied

CD105 (endoglin) expression on hematopoietic stem/progenitor cells.

Endoglin (CD105) is a component of the transforming growth factor-beta (TGF-beta) receptor (TGF-betaR) complex. Together with betaglycan, CD105 is considered as a TGF-betaR accessory molecule (also called TGF-betaRIII), but its functions in the receptor-ligand interactions are still poorly understood. A small subset of human CD34+ hematopoietic stem/progenitor cells that has phenotypic and functional features suggestive of very primitive hematopoietic cells expresses the CD105 antigen. CD34+/CD105+ cells recirculate in the peripheral blood of mobilized subjects and can be purified by immunomagnetic isolation strategies. The hematopoietic potential of these CD34+/CD105+ cells appears to be sustained by a combination of hematopoietic and non-hematopoietic cytokines, which comprises Flt3 ligand, erythropoietin, interleukin-15 and vascular endothelial growth factor. Endogenous TGF-beta1 is a crucial factor for the maintenance of CD34+/CD105+ immaturity acting through positive modulation of both CD105 and CD34 molecules in the absence of relevant effects on the cell cycle profile. CD105 is absent on very primitive CD34-/lineage-/CD45+ (CD34-Lin-) human hematopoietic cells isolated from cord blood. However, in vitro exposure of CD34-Lin- cells to exogenous TGF-beta1 causes the appearance of a discrete population of CD34+/CD105+ cells. Collectively, available data on CD105 expression and function in primitive hematopoiesis indicate that this molecule could cooperate with the dissociation of TGF-beta1 cell cycle effects from its other effects on cell survival and differentiation.

Antigens, CD↗
PubMedDate not supplied

Transplantation of autologous peripheral blood progenitor cells: impact of CD34-cell selection on immunological reconstitution.

Peripheral blood progenitor cells (PBPC) represent an ideal source of stem cells for autologous transplantation because of technical advantages and more favourable engraftment kinetics. The reconstituion of a functional immune system occurs earlier in patients transplanted with cytokine-mobilized autologous PBPC compared with bone marrow; because of the greater T-cell content in PBPC products, donor-derived antigen-specific T-cells transferred with the graft might contribute to short-term immunity in transplant recipients. Despite a prompt reconstitution of B- and T-cell numbers, both B- and T-cell function are profoundly impaired for a prolonged period of time after PBPC infusion. The positive selection of CD34+ cells might provide effective tumor cell purging without compromising hematopoietic recovery in patients with acute leukemia, multiple myeloma, breast cancer and non-Hodgkin's lymphoma, whose autografts have been reported to contain malignant cells which might promote disease relapse. However, the incidence of viral infections in the early posttransplant period might be increased after CD34-selected compared with unmanipulated PBPC transplants, as a result of the lack of accessory and immune cells in the graft. The purpose of this review is to provide an update on immunological reconstitution after transplantation of autologous PBPC; in particular, emphasis will be placed on the mechanisms of immune dysfunction after the infusion of unmanipulated and CD34-selected autografts.

Antigens, CD34↗
PubMedDate not supplied

Docetaxel and epirubicin plus G-CSF as mobilizing treatment to support high-dose chemotherapy in breast cancer.

BACKGROUND: In order to combine an active regimen with a simultaneous efficient mobilization of peripheral blood precursor cells (PBPC), we explored the combination of Docetaxel 75 mg/m2 and Epirubicin 120 mg/m2 with G-CSF 5 mcg/Kg/day s.c. to mobilize PBPC in breast cancer patients to support high-dose chemotherapy (HDC). PATIENTS AND METHODS: Forty patients were enrolled: 27 high risk and 13 metastatic. The entire procedure, including chemotherapy and PBPC collection, was on an outpatient basis. RESULTS: The median day of starting apheresis was day +10 (range 10-12) and the average value of circulating CD34+ cells at peak was 175/microliter (range 33-403). The median yield of CD34+ cells per apheresis was 8.76 x 10(6)/Kg (range 1.83-27.87). None of the patients developed side effects which required hospitalization. All patients enrolled successively received HDC as consolidation treatment. High risk patients received one and metastatic patients two HDC with PBPC reinfusion. All patients obtained a complete engraftment. No significant differences between high-risk and metastatic patients were observed. CONCLUSIONS: Our study suggests that the combination of Docetaxel, Epirubicin, and G-CSF is feasible, safe and efficient outpatient mobilizing treatment for patients with breast cancer receiving HDC.

Adult↗
PubMedDate not supplied

Stem cell-based treatments for gynecological solid tumors.

BACKGROUND AND OBJECTIVE: We have recently assisted to an increasing scientific interest and a new research effort in the field of stem cell-based therapy. Since the late 1980s hematopoietic stem cells (HSC) have been used to set up therapeutic strategies for the treatment of solid tumors such as gynecological cancers. In this context, different approaches have been suggested and clinically investigated. STATE OF THE ART: In the autologous setting we can describe the well-known use of HSC as hematologic support to high-dose chemotherapy regimens, and the use of HSC as a source of dendritic cells for cancer vaccination protocols. In our institution a long-term experience has been developed in high-dose chemotherapy with autologous HSC transplantation as first-line treatment of advanced ovarian cancer, and in the use of cytokines both for HSC collection and for post-transplantation hematopoietic recovery and immune reconstitution. An alternative approach consists of allogenic HSC transplantation following either myeloablative/standard or non-myeloablative/reduced conditioning regimens, which have been proposed as new adoptive immunotherapeutic treatments for different non-hematologic malignancies. PERSPECTIVES: Future strategies in the use of HSC in oncology comprise the possibility of HSC ex-vivo expansion, the use of umbilical cord blood HSC, and the development of HSC-based gene-therapy programs. Further investigations are expected in the new field of cancer stem cells.

Antineoplastic Agents↗
PubMedDate not supplied

Autologous peripheral blood stem cell transplantation in hematological malignancies.

Three patients (2 with high malignant non Hodgkin's lymphomas in partial remission and 1 with acute myeloblastic leukemia in 2nd complete remission) underwent autologous peripheral blood stem cell transplantation (APBSCT). The minimal number of mononuclear cells and CFU-GM collected was 6.18 x 10e8 and 19.77 x 10e4/kg b.w., respectively. Conditioning chemotherapy consisted in BEAM and CVB protocols in non Hodgkin's lymphoma (NHL) patients and busulphan and cyclophosphamide in acute myeloblastic leukemia (AML) patients. All patients achieved complete remission. Bone marrow biopsy performed on day 14 showed complete engraftment. The time to reach 1 x 10e9/l WBC, 0.5 x 10e9/l neutrophil granulocytes and 50 x 10e9/l platelets was no longer than 11, 15 and 8 days, respectively. No major infectious episodes were evident during aplastic phase; fever greater than 38 degrees C was observed in two patients not lasting longer than 2 days. All patients are still in complete remission and continue to have normal hematological values (follow-up lasting 8+ and 3+ months for NHL patients and 4+ months for AML patient).

Adult↗
PubMedDate not supplied

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↗