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Biomedical subjects

A Santoro

Publications and source records attributed to A Santoro.

At least 127 records · Page 7Linked to original sources
PubMed1999

Molecular and clinical remissions in multiple myeloma: role of autologous and allogeneic transplantation of hematopoietic cells.

PURPOSE: To describe molecular monitoring of minimal residual disease in patients with myeloma who have achieved complete remission (CR) after autologous or allogeneic transplantation of hematopoietic cells. MATERIALS AND METHODS: Clonal markers based upon the rearrangement of immunoglobulin heavy-chain genes were generated for each patient and used for polymerase chain reaction (PCR) detection of residual myeloma cells. Fifty-one patients entered the program and 36 achieved CR. After transplantation, molecular monitoring was performed on 29 patients (15 autologous and 14 allogeneic transplants) who had molecular markers. RESULTS: Our data show that molecular remissions are rarely achieved (7%) with high-dose chemotherapy followed by single or double autografting. In addition, virtually all peripheral blood progenitor cell and bone marrow samples contained residual myeloma cells, even when sample collection was scheduled after repeated courses of high-dose chemotherapy. All patients autografted with PCR-positive cells remain positive, and eight of 15 have relapsed. Two patients were autografted with PCR-negative cells: one is in clinical and molecular remission, and one relapsed 25 months after the transplant. In the allografting setting, a higher proportion of patients (50%) achieved molecular remission; there were two relapses, one in the PCR-positive group and one in the PCR-negative group. CONCLUSION: This is the first large study of molecular remissions in myeloma patients to use a PCR-based approach utilizing patient-specific tumor markers. The sizeable fraction of patients who achieved molecular remission after allografting with peripheral blood progenitor cells represents a promising finding in an incurable disease.

Adult↗
PubMed1999

Gemcitabine as a single agent in the treatment of relapsed or refractory aggressive non-Hodgkin's lymphoma.

PURPOSE: A multicenter phase II trial was conducted to evaluate the efficacy and toxicity of gemcitabine in patients with relapsed or refractory aggressive non-Hodgkin's lymphomas (NHL). PATIENTS AND METHODS: Thirty-one patients with B-cell intermediate or high-grade NHL (Working Formulation) were enrolled onto the study. The median age was 61 years, with a Karnofsky performance status of </= 80% in 65% of patients. Forty-eight percent had stage III or IV (Ann Arbor Classification) at study entry. Pretreatment consisted of one, two, or three chemotherapeutic regimens in nine, 11, and 11 patients, respectively. Gemcitabine 1,250 mg/m(2) was administered intravenously over 30 minutes on days 1, 8, and 15 of a 28-day schedule. RESULTS: Thirty patients were assessable for efficacy, and 31 were assessable for toxicity. No complete responses were observed, but six patients showed a partial response, 11 stable disease, and 13 progressive disease. The overall response rate was 20% (95% confidence interval, 8% to 39%) for assessable patients and 19% (95% confidence interval, 8% to 34%) for the intent-to-treat analysis. The median duration of partial response was 6 months (range, 3.7 to 15+ months). Nonhematologic World Health Organization grade 3 toxicity included hepatic toxicity in four patients and infection in two. Hematologic toxicity was observed as grade 3 anemia in three patients, grade 3 leukopenia in two patients, grade 3/4 neutropenia in two patients, and grade 3/4 thrombocytopenia in six patients. CONCLUSION: The present schedule of gemcitabine displays modest efficacy and mild toxicity in pretreated aggressive NHL.

Adult↗
PubMed1999

New reciprocal translocation t(5;10)(q33;q22) associated with atypical chronic myeloid leukemia.

We report a new chromosomal reciprocal translocation t(5;10)(q33;q22) in a 49-year-old man with atypical chronic myeloid leukemia (a-CML) and history of occupational exposure to petroleum products including benzene and other hydrocarbons. The t(5;10) (q33;q22) was found in 94% and 84% of metaphases in peripheral blood and bone marrow cells, respectively. Cytogenetic analysis of single colonies derived from granulocyte-macrophage (CFU-GM), and erythroid (BFU-E) hematopoietic progenitors showed that 88% and 40% of CFU-GM and BFU-E, respectively, had the t(5;10)(q33;q22). In contrast, peripheral blood T-lymphocytes, and cutaneous fibroblasts had normal 46,XY karyotype. Molecular analysis of the t(5;10)(q33;q22) translocation breakpoint is currently underway in order to identify genes located in this region which might provide insights into the pathogenesis of atypical myeloproliferative disorders.

Chromosomes, Human, Pair 10↗
PubMed1999

Ex vivo manipulation of hematopoietic stem cells for transplantation: the potential role of amifostine.

High-dose chemotherapy with autologous stem cell transplantation is an increasingly used procedure in oncohematologic diseases and represents a promising strategy in selected patients with solid tumors. In autologous stem cell transplantation, the risk of reinfusion of clonogenic tumor cells is a remarkable biologic obstacle that can be at least partly overcome by ex vivo graft purging to reduce residual tumor. Mafosfamide and 4-hydroxyperoxycyclophosphamide, active metabolites of cyclophosphamide, are the most widely used pharmacologic agents for ex vivo bone marrow purging. However, in addition to killing tumor cells, they are toxic to normal bone marrow as measured by reduced colony-forming unit granulocyte-macrophage (CFU-GM). Thus, the therapeutic index of these alkylating agents is narrow, and parameters for dose selection must include toxicity to normal bone marrow progenitor cells that can delay bone marrow engraftment and increase risk of infections, bleeding complications, hospitalization, and the need for a costly transplantation procedure. Amifostine (WR-2771, Ethyol; Alza Pharmaceuticals, Palo Alto, CA/US Bioscience, West Conshohocken, PA) selectively protects human CFU-GM progenitor cells from the cytotoxicities of active metabolites of cyclophosphamide without altering its cytotoxic effect on malignant cells. This has been demonstrated both in preclinical and clinical studies in patients with breast cancer, malignant lymphomas, and acute leukemia. Amifostine use during the ex vivo procedure significantly shortened the time to bone marrow engraftment with decreased incidence of infections and need for red blood cell transfusions.

Amifostine↗
PubMed1999

Multiple meningiomas in different neuraxial compartments. Report of two cases.

Multiple meningiomas in different neuraxial compartments are quite rare. The authors report two new cases of association between cranial and spinal meningiomas, one of them in a patient operated upon for multiple intracranial meningiomas. The first case was a 60-year-old woman with progressive paraparesis who had been operated on 13 years earlier for multiple intracranial meningiomas. A myelo-CT scan showed a block of contrast medium at T1-T2; the lesion was removed via a standard laminectomy. The second patient was a 76-year-old woman with a 6-month history of spastic paraparesis. MRI detected an extramedullary intradural lesion at T6-T7. A cerebral MRI, performed because of the onset of seizures, showed a right parietal lesion. Removal of the thoracic lesion was followed, 6 months later, by removal of the cerebral one. Both patients presented a progressive improvement of the paraparesis and returned to normal daily activities.

Aged↗
PubMed1999

Long saphenous-vein grafts for extracranial and intracranial internal carotid aneurysms amenable neither to clipping nor to endovascular treatment.

BACKGROUND: In the treatment of patients with unclippable, uncoilable internal carotid artery aneurysms it may be necessary to use high-flow bypass grafts. The indications, surgical techniques and complications are discussed. METHODS: During a 12- year period, 20 saphenous vein grafts were performed in 20 patients. The 20 aneurysms were located in the prepetrous or intrapetrous internal carotid artery in 7 cases, the intracavernous in 9 and intracranial internal carotid artery in 4. All aneurysms were symptomatic. The vein graft was interposed between the internal carotid artery at the neck and the intrapetrous carotid, from the internal carotid artery at the neck to a branch of the middle cerebral artery, or from the external carotid artery and a branch of the middle cerebral artery, according to the collateral circulation assessed with a 30-minute the balloon test occlusion during electroencephalographic recording. RESULTS: Only one of the 20 grafts occluded. One patient died from a large postoperative cerebral infarction. One patient had cerebral ischemia with transient hemiparesis; and three patients had mixed aphasia that resolved completely within two weeks. Radiological follow-up monitoring was by magnetic resonance imaging, magnetic resonance angiography or digital angiography. Postoperative follow-up ranged from 1 to 12 years (mean 3.7 years). CONCLUSIONS: Our experience in this series suggests that the indications for cerebral revascularization should be widened, even to include patients with adequate collateral circulation, particularly those who have a long life expectancy.

Adult↗
PubMed1999

Malignant cerebellar astrocytomas: clinico-pathological remarks on 10 cases.

BACKGROUND: Malignant glioma represent the 3rd¿4th most frequent cause of death from cancer. The cerebellar site is rare and life expectancy with cerebellar anaplastic astrocytoma is still dismall. The growth and clinical-pathological remarks of the tumor, is similar to the others gliomas of the central nervous system. MRI with Gd is the most useful diagnostic approach but lacks of specificity in detecting highly differentiated neoplasia areas. METHODS: Between 1980 and 1994 10 cases of malignant cerebellar astrocytomas were operated at the Neurosurgical Institute, Department of NeuroSciences, of Roma "La Sapienza" University. All patients were investigated pre-and postoperatively by CT scan with i.v. administration and/or MRI with Gd when possible. RESULTS: Of the 10 patients who followed various protocols, 7 died. Average survival was 13.7 months (range 5-21 months). 3 patients were still alive 12, 15 and 18 months after surgery. In 3 cases (50%) there was also radiological evidence of spinal cord spreading. CONCLUSIONS: Like cerebral lesions, malignant cerebellar astrocytoma still a pathology with a real unsatisfactory prognosis. Our experience probably showed that spinal spreading is underestimated. For this reason we believe that, despite the limited number of cases treated so far, it is important to extend postoperatively the radiotherapy to the entire spinal cord in all patients.

Adolescent↗
PubMed1998

Molecular anatomy of the human glucose 6-phosphate dehydrogenase core promoter.

The gene encoding glucose 6-phosphate dehydrogenase (G6PD), which plays a pivotal role in cell defense against oxidative stress, is ubiquitously expressed at widely different levels in various tissues; moreover, G6PD expression is regulated by a number of stimuli. In this study we have analyzed the molecular anatomy of the G6PD core promoter. Our results indicate that the G6PD promoter is more complex than previously assumed; G6PD expression is under the control of several elements that are all required for correct promoter functioning and, furthermore, a still unidentified mammalian specific factor is needed.

Animals↗
PubMed1998

Early detection of relapse by prospective reverse transcriptase-polymerase chain reaction analysis of the PML/RARalpha fusion gene in patients with acute promyelocytic leukemia enrolled in the GIMEMA-AIEOP multicenter "AIDA" trial. GIMEMA-AIEOP Multicenter "AIDA" Trial.

Although the majority of patients with acute promyelocytic leukemia (APL) are potentially cured by treatments combining all-trans retinoic acid (ATRA) and chemotherapy (CHT), a sizable proportion (around 30%) will relapse during follow-up. Retrospective molecular monitoring studies using reverse transcriptase-polymerase chain reaction (RT-PCR) for the specific PML/RARalpha fusion gene, have shown that a positive test usually precedes the occurrence of hematologic relapse. Prospective RT-PCR analyses were performed since 1993 at diagnosis and at preestablished time intervals during follow-up in bone marrow (BM) samples of 163 patients with PML/RARalpha+ APL enrolled in the multicenter Gruppo Italiano Malattie Ematologiche Maligne dell' Adulto (GIMEMA) trial AIDA (All-trans retinoic acid plus Idarubicin). Treatment consisted of ATRA and idarubicin for induction followed by three polychemotherapy courses as consolidation. The sensitivity level of the RT-PCR assay for PML/RARalpha, as assessed by serial dilution experiments, was 10(-4). All patients were in hematologic remission and tested PCR- at the end of consolidation. Of 21 who converted to PCR-positive thereafter, 20 underwent hematologic relapse at a median time of 3 months (range, 1 to 14) from the first PCR+ result. Seventeen of these 21 (81%) PCR+ conversions were recorded within the first 6 months postconsolidation. Of 142 who tested persistently PCR- in >/=2 tests after consolidation, 8 had hematologic relapse and 134 remained in complete remission (CR) after a median follow-up of 18 months (range, 6 to 38) postconsolidation. Using a time-dependent Cox model, the relative risk of hematologic relapse of patients who converted to PCR+ was 31.8 (confidence limits 95%, 12.9 to 78.3). Our results indicate that conversion to PCR positivity for PML/RARalpha during remission is highly predictive of subsequent hematologic relapse and highlight the prognostic value of stringent molecular monitoring during the early postconsolidation phase in APL. As a result of the present study, salvage treatment in patients enrolled in the GIMEMA trial AIDA is now anticipated at the time of molecular relapse, defined as the conversion to PCR positivity in two successive BM samplings during follow-up.

Adolescent↗
PubMed1998

Genotoxicity and oxidative stress induced by pesticide exposure in bovine lymphocyte cultures in vitro.

The genotoxic activity of the pesticides gliphosate, vinclozolin and DPX-E9636 was studied in in vitro cultures of bovine lymphocytes, using chromosome aberration (CA) and sister chromatid exchange (SCE) frequencies as genetic end-points and a variation of glucose 6-phosphate dehydrogenase (G6PD) enzyme activity as a marker of changes in the normal cell redox state. Results indicated a statistically significant increase of structural aberrations, sister chromatid exchanges and G6PD activity, suggesting that the pesticides tested induce either oxidative stress or a mutagenic effect in this species. The evaluation of both mitotic index and cell viability, after pesticide exposure, demonstrates a high cytotoxic effect which is always associated with the observed genotoxic effect.

Animals↗
PubMed1998

Total removal of an intramedullary cavernous angioma by transthoracic approach.

Intramedullary cavernous angiomas are rare vascular malformations; all published cases have been surgically approached posteriorly by standard laminectomy. We describe the case of a 63-year-old man with an intramedullary cavernous angioma, anteriorly located in the thoracic spinal cord. The angioma was operated on by transthoracic approach and totally removed.

Brain Neoplasms↗
PubMed1998

Blood volume regulation during hemodialysis.

Hemodialysis (HD)-induced hypotension may be precipitated by severe hypovolemia. To avoid the appearance of destabilizing hypovolemias, we have developed a biofeedback control system for intradialytic blood volume (BV)-changes modeling. The system, incorporated in a dialysis machine, is based on a multivariable closed-loop control with a dependent output variable, the BV changes, and two independent control variables, the ultrafiltration rate (Qf) and dialysate conductivity (DC). The relative BV changes occurring during HD are measured by an optical device. The Qf and DC are continuously adjusted by the control model during the treatment to minimize any discrepancies between the ideal targets for the BV, the patient's body weight reductions, and the experimentally obtained results. The system manages three kinds of errors: in BV changes, the total weight loss, and the sodium balance. The latter is controlled by a dedicated kinetic model that continuously calculates the equivalent DC and, by the end of the session, tends to make the sodium balance the same as the one obtained in conventional HD with constant DC. This system's capacity to improve intradialytic hemodynamic tolerance has been assessed in a crossover study of eight highly symptomatic patients. Conventional HD (CHD; period A) was compared with blood volume-controlled dialysis sessions (BV-CHD; period B) following a protocol with an A1-B-A2 sequence, with each period lasting 1 month. A lower decrease in BV (-10.6%) was obtained during BV-CHD (period B) compared with CHD (-12.3% in period A1 and -12.5% in period A2). The predialysis to postdialysis systolic arterial pressure changes were lower in period B (-12.4%) than in period A (-20% in A1 and -17.5% in A2; P < 0.05) despite similar total Qf and mean treatment times. A significant reduction in the number of severe hypotensive episodes (three in period B v 26 in period A1 and 16 in period A2; P < 0.05) and the overall incidence of complaints, especially of muscular cramps, was found in BV-CHD. These results were reflected in a reduced need for therapeutically administered isotonic saline in each session (60 mL in B v160 mL in A1 and 95 mL in A2; P < 0.05). In conclusion, the proposed biofeedback system for intradialytic BV control may be useful to avoid severe hypovolemic states, to stabilize BV by modeling its trend, and to avoid reaching individual critical BV thresholds in hypotension-prone patients.

Blood Pressure↗
PubMed1998

Visual improvement during octreotide therapy in a case of episellar meningioma.

Meningiomas of the tuberculum sellae can induce compression of the optic tract. We report the case of a 54-year-old female patient affected by a suspected pituitary macroadenoma with severe visual field defects, who experienced a significant clinical and visual improvement during short-term octreotide therapy, contrasting with the lack of neuroradiological evidence for tumor shrinkage. The patient subsequently underwent transcranial surgery with a final diagnosis of meningioma. The putative mechanisms of visual improvement during octreotide therapy are discussed.

Adenoma↗
PubMed1998

Modulating effect of lonidamine on response to doxorubicin in metastatic breast cancer patients: results from a multicenter prospective randomized trial.

Previous results from our preclinical studies have shown that lonidamine (LND) can positively modulate the antiproliferative activity of doxorubicin (DOX) on breast cancer cell lines. To evaluate the effect of LND in a clinical setting, a multicenter randomized trial was carried out on patients with advanced breast cancer. From September 1991 to July 1993, 181 patients were enrolled in the trial and received an initial treatment of DOX at 75 mg/m2 for 3 cycles. The 137 patients who reached complete remission, partial remission, or stable disease were randomized to receive either DOX alone (75 mg/m2 day 1) (arm A) or DOX plus LND (600 mg orally/day) (arm B). The patients enrolled in the two arms were fairly homogeneous in terms of major clinical characteristics. Toxicity was similar in both arms except for myalgia: WHO grade > or=2 was observed in 57% of arm B patients. Overall response rate to DOX + LND was 50% and to DOX alone 38% in evaluable patients, and 48% vs 37% in all registered patients, as determined by an intention-to-treat analysis. The differences did not reach statistical significance. Conversely, in agreement with previous findings, we observed a significant difference in response rate in the subgroup of patients with liver metastases, regardless of the extent of hepatic involvement (DOX + LND 68% vs DOX 33%, p=0.03). This observation makes LND an important tool in association with anthracyclines in the treatment of this subgroup of patients.

Adult↗
PubMed1998

Soluble interleukin-2 receptors (sIL-2R) in Hodgkin's disease: outcome and clinical implications.

The aim of this study was to assess the prognostic role of soluble interleukin-2 receptors (sIL-2R) in Hodgkin's disease (HD) both in the achievement of complete remission (CR) and in predicting disease relapse. Between August 1988 and June 1993 sIL-2R serum levels were measured in 174 untreated patients; in 137 of them evaluation was repeated at the end of treatment and in 132 also during the follow-up. Baseline sIL-2R levels (mean+/-standard error) were significantly higher in patients than in 65 healthy control subjects (1842+/-129 U ml(-1) vs 420+/-10 U ml(-10, P< 0.0001). At the end of treatment 135 out of 137 evaluated patients achieved complete response (CR) and their mean sIL-2R serum levels were significantly lower than those at diagnosis (635+/-19 U ml(-1) vs 1795+/-122 U ml(-1), P=0.0001). After a median follow-up of 5 years, sIL-2R remained low in 114 patients in continuous CR, while they increased in 9 out of 12 patients (75%) who relapsed. However, a temporary increase was also observed in six patients (5%) still in CR. Treatment outcome in terms of freedom from progression was linearly related to sIL-2R levels. Our study confirms that patients with untreated HD have increased baseline levels of sIL-2R compared with healthy subjects and that their pretreatment values may be an indication of disease outcome similar to other conventional prognostic factors, such as number of involved sites, presence of B symptoms and extranodal extent.

Adolescent↗
PubMed1998

Allogeneic transplantation of unmanipulated peripheral blood stem cells in patients with multiple myeloma.

In multiple myeloma (MM), allogeneic bone marrow transplantation may produce complete and durable responses, but is accompanied by significant transplant-related mortality (TRM). To assess feasibility and possible advantages offered by the use of allogeneic, growth factor-primed PBSC instead of marrow, we analyzed the data of 10 patients with MM (IgG = 6, IgA = 1, BJ = 2, non-secreting = 1; stage II = 1, stage III = 8, plasma-cell leukemia = 1) who received an allogeneic transplant with PBSC. Their age ranged between 35 and 53 years (median 45). All were HLA-identical to their sibling donors. Prior to allograft, six patients received standard-dose chemotherapy (DAV or CY-Dexa) and four a sequential intensified scheme with autologous PBSC support. At the time of transplantation, three patients were in CR, three in PR, three had refractory disease, one progressive disease. Patients were conditioned with busulfan-melphalan (n = 9) or busulfan-cyclophosphamide (n = 1), and were allografted with unmanipulated PBSC obtained by apheresis after treatment with G-CSF alone (n = 6) or GM-CSF followed by G-CSF (n = 4). All patients engrafted, with 0.5 x 10(9)/l PMN and 50 x 10(9)/l platelets on (median) day 13. Four patients had > or =grade II acute GVHD (grade II in 3, grade III in 1). Following allograft, CR was achieved in 71% patients. Eight are currently alive, with six in CR at a median of 18.5 months (range 7-28) from the transplant. Two patients died, 1 and 4 months from the allograft, respectively, and one is alive with progression. A PCR analysis of IgH rearrangement showed that residual disease was no more molecularly detectable in four out of seven evaluated patients following allograft. The results suggest that PBSC may improve the therapeutic efficacy of allogeneic transplant in MM, not only by a reduction of TRM but also by an improvement of rate and quality of response.

Adult↗