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Biomedical subjects

A Santoro

Publications and source records attributed to A Santoro.

At least 145 records · Page 8Linked to original sources

PBSC mobilization, collection and positive selection in patients with chronic lymphocytic leukemia.

We report the results of PBSC mobilization and immune selection in 17 patients with advanced chronic lymphocytic leukemia (CLL) enrolled in a multicenter Italian study of autologous transplantation with peripheral CD34+ selected cells. Mobilization was achieved by cyclophosphamide (CY) 4 g/m2 + G-CSF 5 microg/kg. CD34+ cells were positively selected by means of avidin-biotin immunoaffinity columns (Ceprate SC) or immunomagnetic beads (Isolex 300i) systems. Evaluation of minimal residual disease was performed by PCR analysis of the IgH gene rearrangment on the apheresis product before and after selection. Our results showed that after CY a median of 3.6 x 10(6)/kg (0.5-12.8) CD34+ cells were collected with a median of two aphereses in 14 out of 17 patients; three failed to mobilize a number of CD34+ cells adequate for subsequent manipulation. We found that in CR patients CD34+ cell yield per apheresis was significantly higher than in PR patients (P < 0.05). Sixteen selection procedures were performed in 13 patients. CD34+ cell recovery was 33.5% (10-85) with a median final yield of 1 x 10(6)/kg CD34+. Two patients underwent marrow collection due to the low number of CD34+ cells recovered. Final purity was 59% (range 22-94) and CD5/20+ cell depletion was 2.7 log (1.6-4.4). Our data showed a statistically higher CD34+ cell recovery and purity with the Isolex device compared to Ceprate (P < 0.01 and 0.01, respectively). All the evaluable samples remained PCR positive after selection. The main issues to be addressed in the future are the identification of patients who fail mobilization and the improvement of purging methods.

Adult↗

Ifosfamide and vinorelbine: an active regimen for patients with relapsed or refractory Hodgkin's disease.

Twenty-six patients with relapsed or refractory Hodgkin's disease (HD) were treated with an intensive salvage regimen combining ifosfamide (3000 mg/m2/d, days 1-4 through continuous intravenous infusion) and vinorelbine (25 mg/m2, i.v. days 1 and 5) with mesna uroprotection and G-CSF support. Courses were given at 3-week intervals. Ten patients achieved a complete and 10 patients a partial response, yielding an overall response rate of 77%. The main toxic effect was neutropenia and the combination was well tolerated.

Adult↗

Primary non-Hodgkin's lymphoma of the liver: case report.

This paper describes a rare occurrence of primary lymphoma of the liver in a young female and demonstrates the possibility of making the correct diagnosis by ultrasonically guided fine needle aspiration biopsy. A 32-year old female suffering from upper abdominal pain, hepatomegaly, nausea, anorexia and weight loss for almost 2 months was admitted to our Department. After a clinical and instrumental (lab exams, ultrasonography, computed tomography) evaluation, we reached the correct diagnosis of hepatic primary non-Hodgkin's lymphoma by means of ultrasonically guided fine needle aspiration biopsy. Two weeks after hospitalization the patient was treated with 8 cycles of CHOP chemotherapy and then with alpha-2b interferon immunotherapy. The hepatic ultrasonography and CT abdominal scan showed the complete absence of the lymphomatous lesions 36 months later. Up to February 1998, the patient was well and led a normal life. We conclude that the CHOP chemotherapy plus interferon immunotherapy were effective and well tolerated with a complete response 38 months following diagnosis.

Adult↗

Cytogenetic damage and induction of pro-oxidant state in human lymphocytes exposed in vitro to gliphosate, vinclozolin, atrazine, and DPX-E9636.

We analyzed chromosome aberrations (CAs), sister chromatid exchanges (SCEs), mitotic index (MI), and glucose 6-phosphate dehydrogenase (G6PD) enzyme activity in human peripheral lymphocytes from three healthy donors exposed in vitro to different concentrations of gliphosate, vinclozolin, atrazine, and DPX-E9636. The pesticides gliphosate, vinclozolin, and atrazine have been studied in a broad range of genetic tests with predominantly conflicting or negative results, whereas little is known about the genotoxicity of DPX-E9636. In our experimental conditions, each chemical compound tested produced a dose-related increase in the percent of aberrant cells and an increase of SCE/cell. Furthermore, at the highest concentrations of vinclozolin, atrazine, and DPX-E9636, we observed a significant reduction of the mitotic index. The increase of G6PD activity in exposed lymphocyte cultures strongly indicated an induction of a pro-oxidant state of the cells as an initial response to pesticide exposure.

Atrazine↗

Treatment of aneurysms unsuitable for clipping or endovascular therapy.

A small percentage of aneurysms cannot be treated by traditional techniques. The majority of these are giant aneurysms, whose dimensions exceed 2.5 cm, which are particularly difficult to treat because of their anatomical characteristics. Clinically, they may present with compressive, ischemic or hemorrhagic symptoms. Treatment of intracavernous aneurysms and those of the pre- and intrapetrous segment of the internal carotid artery represent a challenge for the neurosurgeon and on occasion may not be suitable for clipping or endovascular techniques. This is true for aneurysms without a well-defined neck and fusiform aneurysms, for which extra-intracranial bypass using a graft of saphenous vein plays a fundamental role. The method used for bypass depends on whether there is sufficient collateral flow. The authors emphasize that it is not possible to identify patients who can be submitted to therapeutic occlusion of the internal carotid artery without the risk of late ischemic attacks or de novo aneurysm formation.

Cerebral Revascularization↗

bcr-abl rearrangement in adult T-lineage acute lymphoblastic leukemia.

The bcr-abl rearrangement in T-lineage ALL has been rarely described. In the last three years we studied all new patients with ALL at diagnosis by cytogenetic and molecular analysis. Three out of eleven T-lineage ALL patients presented the rearrangement and only one was Philadelphia positive.

Adolescent↗

Distribution and behavior of Listeria monocytogenes in three lots of naturally-contaminated vacuum-packed smoked salmon stored at 2 and 10 degrees C.

The incidence, the number and the behavior of L. monocytogenes in three lots of naturally-contaminated vacuum-packed sliced smoked salmon, processed in different plants, were investigated during storage at 2 and 10 degrees C. L. monocytogenes was isolated from 20 of the 100 packages stored at 2 degrees C (16 from lot 1, 1 from lot 2 and 3 from lot 3) and from 12 of the 65 packages stored at 10 degrees C (all from lot 1). The levels detected were 15, 20, 290, 1100 and > 1100 cfu/g in 5 packages, all belonging to lot 1, and < 10 cfu/g in the remaining samples. The high incidence of L. monocytogenes in lot 1 was assumed to be due mainly to the use of causal workers for the slicing and packing operations.

Animals↗

Changes in the distribution of actin-associated proteins in psoriatic keratinocytes. Immunohistochemical study using confocal laser scanning microscopy.

Recent studies support the presence of adherens junctions at the dermal-epidermal interface in addition to hemidesmosomes. In this area the integrin/actin-containing cytoskeleton connection occurs by means of a complex of proteins called actin-associated proteins (talin, vinculin, alpha-actinin). As previous studies have demonstrated the presence in psoriatic lesions of marked alterations in both the basement membrane molecular composition and the polarized expression of integrins, we decided to determine whether alterations in the behaviour of the actin-associated proteins could be demonstrated. We thus undertook an immunolocalization study with monoclonal antibodies directed against talin, vinculin, and alpha-actinin in cutaneous biopsies taken from involved and uninvolved skin of 12 patients with extensive chronic plaque psoriasis. The findings showed an almost total lack of reaction against talin and vinculin in the basal layer and an increased positivity against the proteins in the suprabasal layers. Similar, though less marked, alterations were present in uninvolved psoriatic skin. These results, in agreement with those of previous studies, confirm serious alterations in the matrix protein/cytoskeleton connection system, and support the hypothesis that this condition may play a key role in the pathogenesis of the disease.

Actinin↗

Cavernoma of the cavernous sinus: case report.

BACKGROUND: The authors report a case of extra-axial cerebral cavernoma localized at the level of the cavernous sinus. This pathology is extremely rare, therefore, differential diagnosis with tumors such as meningioma is often difficult. During recent years, surgical indications for these lesions, congenital and rarely hereditary, have become more definite due to the considerable progress made in neuroradiologic and microsurgic techniques as well as better anatomic knowledge of this region. METHODS: This 49-year-old man was admitted with a 1-year history of diplopia. Cranial computed tomography (CT) scan with contrast medium, performed prior to admission, showed an expansive lesion at the level of the right cavernous sinus. Preoperative neuroradiologic diagnosis, after cerebral magnetic resonance imaging (MRI) with gadolinium enhancement and cerebral panangiography, was probable cavernoma. The lesion was totally removed via a fronto-orbito-temporo-zygomatic craniotomy. RESULTS: Postoperatively, the patient had a right oculomotor nerve palsy. This spontaneously resolved 8 months after surgery; diplopia also completely disappeared. Early postoperative control MRI scans with gadolinium on the 2nd postoperative day and 3 months after operation confirmed total removal of the lesion. CONCLUSIONS: The clinical onset and neuroradiologic aspect of these lesions and the fact that they rarely involve the cavernous sinus, may sometimes make preoperative diagnosis of cavernous sinus cavernoma difficult. Nevertheless, given the routine use of microsurgical techniques and improved anatomic knowledge of this delicate region, the treatment of choice is surgery. However, when doubts exist regarding achievement of total removal, radiosurgery is still a valid therapeutic tool.

Brain Neoplasms↗

Initial chemotherapy for primary resectable large-cell lymphoma of the stomach.

BACKGROUND: We aimed to evaluate the safety and effectiveness of a conservative approach with short-term chemotherapy with or without consolidation radiotherapy in primary resectable large-cell gastric lymphoma in patients not requiring emergency surgery at presentation. PATIENTS AND METHODS: Seventeen consecutive patients presenting with resectable primary large-cell lymphoma of the stomach not requiring immediate surgery were initially treated with chemotherapy with or without consolidation radiotherapy. Subtotal or total resection of the stomach was planned only as salvage treatment for those patients who failed locally, or as emergency surgery in instances of acute iatrogenic complications of treatment. Chemotherapy included four to six cycles of an anthracycline-containing regimen, and consolidation radiotherapy was planned on the entire stomach and surrounding lymph node areas for complete responders readily capable of compliance with a daily treatment schedule at our Institution. RESULTS: None of the patients in the present series experienced acute iatrogenic morbidity or mortality from local complications. After a median follow-up of almost six years, two patients failing first-line chemotherapy have died of progressive lymphoma, while 15 patients are well and currently disease-free. CONCLUSIONS: Up-front chemotherapy as initial treatment for primary gastric large-cell lymphoma appears to be a safe and effective treatment by which most patients can probably be spared surgical gastrectomy. Consolidation radiation therapy on the stomach can probably improve on the effectiveness of chemotherapy alone. More experience is needed to elucidate the prognostic factors, treatment-related long-term toxic effects and the feasibility of such a treatment administered outside of highly specialized institutions.

Adult↗

Quality of life assessment and clinical decision-making.

Survival and quality of life are the two end-points of cancer treatment. Recommendations are available as to how quality of life should be assessed in clinical studies in order for quantitative scores to be provided for it, along with survival data. The two measurements can be combined, and their total should yield a definition of the state of the art in cancer treatment with respect to both the quantity and the quality of life. However, at the individual level, quality of life can be traded off against survival only by taking into account the patient's attitude toward risk. More importantly, the quality of health status may be valued in a completely different way from patient to patient. Thus, when a clinical choice is to be made from among different treatment options, the ethical principle of respect for the patient's autonomy would require that the patient be informed of their possible respective outcomes, and allowed to provide his/her own assessment of the quality of life associated with these outcomes. This might have consequences for quality of life assessment in clinical studies, which should not only quantify average scores for treatment comparisons, but also provide a 'health state description' with respect to the aftermath of each of the treatment options. These data could be formalized in the already proposed decision instruments incorporating clinical scenarios for patient information. In any case, this should allow individualized clinical decisions incorporating each patient's preferences for the quality of his/her expected life span. Providing average quality of life scores may be useful, indeed, for population-based health decisions, as are those on resource allocation and those on registration of new drugs.

Clinical Medicine↗

Successful engraftment of allogeneic PBSC after conditioning with busulfan alone.

A 44-year-old woman with AML, while receiving a conditioning treatment with BU-CY for an allogeneic sibling transplant, developed septic shock with pulmonary embolism and heart failure. Conditioning was stopped at the end of the busulfan course and cyclophosphamide omitted. After antibiotics, dopamine and steroids the patient was allografted, using the donor's G-CSF-primed PBSC. She recovered her peripheral blood counts promptly and developed an acute GVHD grade II that responded to steroids. The DNA microsatellite analysis showed full donor engraftment up to a year from transplantation. This case suggests that the use of PBSC may facilitate engraftment in the absence of an effective immunosuppression during conditioning.

Adult↗

Allogeneic peripheral blood progenitor cells for treatment of relapse after bone marrow transplantation.

Donor leukocyte infusions (DLI) are an effective therapy for patients who relapse with leukemia after bone marrow transplantation (BMT). Severe graft-versus-host disease and prolonged periods of pancytopenia compromise the success of this treatment in a substantial number of patients. We used filgrastim-mobilized peripheral blood progenitor cells (PBPCs), in some cases preceded by cytoreductive therapy, to circumvent some of the problems associated with DLI. Eleven patients (median age 41 years) received a total of 20 donor cell infusions. Their diagnosis was CML in hematological (two patients) or cytogenetic relapse (two patients), six patients suffered from acute myeloid leukemia (AM; n = 5) or Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL Ph+). One patient had multiple myeloma (MM). All six patients with acute leukemias received cytoreductive therapy prior to PBPC infusions; three patients with CML were pretreated with IFN alpha. Four of four patients with CML responded to PBPC infusions and currently are in complete clinical and molecular remission for time periods between 1 and 12 months. Six of six patients with acute leukemias achieved a complete remission. All of them relapsed after a median remission duration of 24 weeks (range 11-49 weeks). Three patients relapsed at extramedullary sites (CNS, testes, skin). Four of six acute leukemia patients received further cytoreductive therapy. All patients responded again and are in complete remission for time periods between 14 and 615 days. Two patients with acute leukemias have died due to dissemination of the disease. The patient with MM did not respond and is alive with disease. Severe (grade III) acute GVHD developed in two of 11 patients, three patients developed grade II disease, six patients did not show any signs of GVHD. Extensive chronic GVHD has developed in two cases to date. Patients with chemotherapy prior to PBPC infusion developed neutropenia and thrombocytopenia with a maximum duration of 20 and 14 days, respectively; prolonged periods of neutropenia did not occur. Two patients developed long-lasting thrombocytopenia in spite of PBPC infusion, in one case followed by leukemic relapse. Repeated courses of chemotherapy and PBPC infusion were generally tolerated well; no early deaths due to treatment-related toxicity or GVHD were observed. We conclude that the use of allogeneic PBPC instead of DLI in patients with relapse after BMT is technically feasible and safe. The efficacy of PBPC infusions seems comparable to DLI in patients with CML. Patients with acute leukemias also achieved complete albeit transient remissions. Aggressive chemotherapy followed by PBPC infusions resulted in only limited duration of cytopenia. The usage of PBPC infusion instead of non G-CSF-mobilized donor cells for treatment of relapse after BMT may reduce pancytopenia-related complications and merits further investigation.

Adult↗

Outcome of patients with Hodgkin's disease failing after primary MOPP-ABVD.

PURPOSE: This study analyzed long-term results in patients with Hodgkin's disease who were resistant to or relapsed after first-line treatment with MOPP and ABVD. Response to salvage treatments and prognostic factors were also evaluated. PATIENTS AND METHODS: The study population included 115 refractory or relapsed patients among a total of 415 patients treated with alternating or hybrid MOPP-ABVD followed by radiotherapy (25 to 30 Gy) to initial bulky sites. The median follow-up duration of the present series was 91 months. Thirty-nine of 115 patients (34%) showed disease progression while on primary treatment (induction failures); 48 relapsed after complete remissions that lasted < or = 12 months and 28 after complete remission that lasted more than 12 months from the end of all treatments. RESULTS: At 8 years, the overall survival rate was 27%, being 54% and 28% in patients whose initial complete remission was longer or shorter than 12 months, respectively, and 8% in induction failures (P < .001). Response to first-line chemotherapy and disease extent at first progression significantly influenced long-term results, as well as the incidence and duration of complete remission. CONCLUSION: The present data confirm previous observations that showed the main prognostic factors to influence outcome after salvage treatment are response duration to first-line therapy and disease extent at relapse. The results indicate that patients who relapse after the alternating MOPP/ABVD regimen have a prognosis similar to that of patients who relapse after a four-drug regimen (MOPP or ABVD alone). Re-treatment with initial chemotherapy seems the treatment of choice for patients who relapse after an initial complete remission that lasts greater than 12 months, while the real impact of high-dose chemotherapy or new regimens should be assessed in resistant patients.

Adult↗

Transplantation of unmanipulated allogeneic PBSC: preliminary report on 24 patients.

To explore the feasibility and potential advantages of PBSC in allogeneic transplantation, we grafted 24 patients (age 16-57, median 37) with different hematologic diseases (ALL = 10, AML = 5, MM = 4, NHL = 2, CML = 1, MDS = 1, AA = 1), 23 HLA-identical to their siblings and 1 partially matched. Cells were collected from donors by apheresis after G-CSF 10 to 16 mg/kg/day for 4 to 5 days, and stored at 4 degrees C until infusion. The patients were conditioned with chemotherapy regimens including busulfan and cyclophosphamide in the majority of cases and received GVHD prophylaxis with CSA-MTX in all but two. The graft consisted of PBSC alone, with a median of 143.5 (range 18.1-358.9) x 10(4)/kg CFU-GM, 9.0 (range 3.3-18.0) x 10(6)/kg CD34+ cells and 2.8 (range 1.2 to 8.6) x 10(8)/kg CD3+ and cells. An ANC >0.0.5 x 10(9)/L was recovered on (median) day 13 (range 11-17), and a platelet count >50 x 10(9)/L on (median) day 13 (range 12-55) post graft. There was no correlation between CD34+ cells or CFU-GM number in the inoculum and time to hematologic reconstitution. Acute GVHD (grade II-IV) occurred in 10 out of 22 (45%), chronic GVHD in 10 out of 18 evaluable (55%) patients. We found no relationship between occurrence of acute or chronic GVHD and number of CD3+ cells in the graft. Four patients relapsed and 7 died after transplantation. Fifteen patients are currently alive and disease-free 67 to 710 (median 286) days from the graft. Allogeneic transplantation with unmanipulated PBSC ensures a fast and stable engraftment. Acute GVHD incidence and severity seems comparable to that of bone marrow transplantation, but there may be an increase in chronic GVHD, mainly of the extensive form.

Adolescent↗