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Biomedical subjects

R Miniero

Publications and source records attributed to R Miniero.

At least 91 records · Page 5Linked to original sources
PubMed1995

Extended intrathecal methotrexate may replace cranial irradiation for prevention of CNS relapse in children with intermediate-risk acute lymphoblastic leukemia treated with Berlin-Frankfurt-Münster-based intensive chemotherapy. The Associazione Italiana di Ematologia ed Oncologia Pediatrica.

PURPOSE: To assess the effect of treatment intensification and that of extended intrathecal methotrexate substitution for cranial irradiation in intermediate-risk acute lymphoblastic leukemia (ALL) children treated with a Berlin-Frankfurt-Münster (BFM)-based intensive chemotherapy. PATIENTS: Three hundred ninety-six children with non-B-ALL were enrolled onto the Associazione Italiana di Ematologia ed Oncologic Pediatrica (AIEOP) ALL 88 study. Standard risk (SR) included patients with low tumor burden (BFM risk index [RI], < 0.8); intermediate risk (IR) were patients with an RI > or = 0.8 but less than 1.2; and high risk (HR) were those with an RI > or = 1.2 or CNS involvement at diagnosis. The treatment schedule was a modified version of the ALL-BFM 86 study. CNS-directed treatment consisted of high-dose methotrexate (HD-MTX; 5 g/m2 for four courses) plus intrathecal methotrexate (IT-MTX; nine doses); IR patients additionally received extended IT-MTX (nine doses during continuation therapy); cranial irradiation was given only to HR patients. RESULTS: Of the 375 (94.7%) children who achieved remission, 1.3% had an adverse event other than relapse. The estimated event-free survival (EFS) at 6 years was 66.6% (SE 2.4) overall; 80.7% (4.5) in the SR patients, 77.5% (3.9) in the IR patients, and 54.5% (3.7) in the HR patients. Relapse occurred in 107 children (27.0%). Isolated CNS relapse occurred in 20 children (5.0%): 5 (6.3%) in the SR group, 1 (0.8%) in the IR group, and 14 (7.1%) in the HR group. The estimated 6-year CNS leukemia-free survival was 94.6% (1.2) overall: 93.5% (2.8) in the SR group, 99.1% (0.9) in the IR group, and 92.3% (2.0) in the HR group. CONCLUSION: Cranial irradiation may be omitted safely in IR ALL patients treated with BFM-based intensive chemotherapy when extended intrathecal chemotherapy is given. Because the CNS disease control was less complete in the SR group, these data challenge the effectiveness of HD-MTX for protection from CNS disease and support the protective role of extended intrathecal chemotherapy.

Adolescent↗
PubMed1995

Treatment of childhood acute lymphoblastic leukemia in second remission with allogeneic bone marrow transplantation and chemotherapy: ten-year experience of the Italian Bone Marrow Transplantation Group and the Italian Pediatric Hematology Oncology Association.

PURPOSE: To compare the results of allogeneic bone marrow transplantation (AlloBMT) with those obtained with chemotherapy (CHEMO) in children with acute lymphoblastic leukemia (ALL) in second complete remission (CR) after a marrow relapse. The experience of the Italian Bone Marrow Transplantation Group and the Italian Pediatric Hematology Oncology Association is summarized. PATIENTS AND METHODS: All children who had a relapse in the period 1980 to 1989 in 27 centers in Italy were eligible for the study. Of 287 eligible patients, 230 were treated with CHEMO, most of them (93%) according to a standard multiple-drug relapse protocol. The remaining 57 children underwent AlloBMT. Preparative regimens included total-body irradiation and chemotherapy (n = 51) or chemotherapy alone (n = 6). Statistical analysis was performed with a Cox regression model adjusting for waiting time to transplant and prognostic factors. RESULTS: In the whole series, minimum and median follow-up after second CR were 3 and 6.2 years, respectively; at 8 years from second CR, disease-free survival (DFS) was 20.0% (SE 2.5) and survival was 26.4% (SE 2.9). In the group of patients with an early first relapse, DFS was significantly longer after AlloBMT than after CHEMO (relative risk [RR] = 0.45, P = .002). No significant advantage of AlloBMT over CHEMO was found for patients with a late relapse (> 30 months since diagnosis). Duration of first CR significantly influenced prognosis in the CHEMO group (RR = 0.32, P = .0001 for patients with late first relapse versus patients with early first relapse). CONCLUSION: Results suggest an advantage in DFS of AlloBMT over CHEMO in ALL patients who experienced an early first medullary relapse. Prospective trials are needed to address efficacy of AlloBMT versus CHEMO in patients with late bone marrow relapse.

Adolescent↗
PubMed1995

Hepatocellular codistribution of c100, c33, c22, and NS5 hepatitis C virus antigens detected by using immunopurified polyclonal spontaneous human antibodies.

Hepatitis C virus (HCV) antigens in liver biopsy have been detected by immunohistochemistry using both spontaneous human IgG and murine monoclonal or rabbit polyclonal monospecific reagents. Conflicting results have been obtained in different studies. This was probably because of the incapacity of single experimental antibodies, raised against synthetic or recombinant peptides, to recognize native tissue antigens. To overcome this possibility, we immunopurified monospecific spontaneous polyclonal human Ig, therefore induced by native antigens, from the single antigen-containing bands of RIBA 3 strips. Antibodies to c100, c33, c22, and NS5 antigens were obtained from the serum of a patient affected by chronic hepatitis C. The IgG fraction of this serum had proved to stain tissue HCV antigens. Eight biopsies were selected on the basis of strong hepatocellular reactivity with the whole IgG fraction in a variable number (from 5% to 75%) of cells. The four antigens were detected in all biopsies; a clear cellular codistribution was observed on serial sections. These data demonstrate that the possibility to identify HCV antigens in liver biopsies is higher when using human antibodies induced by native antigens rather than experimental antibodies. The approach of immunopurification of human antibodies can be extended to other HCV-related epitopes to obtain reagents useful for the selection and optimization of monoclonal or polyclonal antibodies.

Antigens, Viral↗
PubMed1995

HLA-haploidentical umbilical cord blood stem cell transplantation in a child with advanced leukemia: clinical outcome and analysis of hematopoietic recovery.

Growing attention has been focused on cord blood as a source of transplantable hematopoietic stem cells. However, clinical experience is rather limited. In this study we describe a child with advanced acute lymphoblastic leukemia who received an HLA-haploidentical cord blood transplant. The patient was transplanted in third complete remission after conditioning with fractionated total body irradiation, thiotepa and cyclophosphamide. Forty-one milliliters of cryopreserved umbilical cord blood, containing 0.15 x 10(8) nucleated cells/kg and 0.25 x 10(4) CFU-GM/kg, were infused. Cyclosporine and prednisone were administered for graft-versus-host disease (GVHD) prophylaxis. The patient received G-CSF from day +1 to day +35, but no improvement in granulocyte counts was observed. Therefore, administration of GM-CSF was started on day +36 to day +59, which resulted in a significant increase in white blood cells and granulocyte counts. Sustained myeloid engraftment was evidenced by a granulocyte count > 0.5 x 10(9)/l by day +41. The presence of donor-derived cells could be documented in the peripheral blood and bone marrow of the patient by cytogenetic analysis, HLA phenotyping and DNA studies. Forty-one days after transplant, clonogenic bone marrow assays showed the presence of low frequencies of primitive hematopoietic progenitor cells (BFU-E = 19/10(5) and CFU-GM = 8/10(5)). The chimerism was complete and no host-derived cells could be detected. However, the engraftment was restricted to the myeloid lineage whereas lymphoid and megakaryocytic engraftments were inadequate. The immunophenotype of the patient's peripheral blood showed the presence of T lymphocytes expressing an immature phenotype (CD2+ CD3-) at day +21.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗
PubMed1995

[Treatment of metastatic osteosarcoma with verapamil, cyclosporine and chemotherapy. A case report].

Studies on the use of revertants to overcome MDR have aroused a great interest even if they failed to prove their actual usefulness. A case of 10 years and 6 months old boy is described. He suffered from osteoblastic osteosarcoma and underwent chemotherapy following CNR-NEO3 protocol, wide surgical resection and postoperative chemotherapy. Nineteen months after diagnosis he underwent the removal of a little subpleural nodule in the right lung. Forty-five days later, in the same site, a large local metastasis was observed together with many others secondaries localizations spred in both lungs. Because of the rapid evolution they were considered not suitable for surgical treatment. A cyclosporine and verapamil treatment in association with adryamicin and etoposide was begun with the aim overcoming multidrug resistance. Five treatments were provided. ECG monitoring during verapamil infusion did not show any trouble; mielotoxicity was mild, with no need of transfusions. A lung CT scan at the end of the therapy demonstrated an important decrease of the subpleural metastasis and the vanishing of lung nodules. Another surgical intervention was provided together with 2 postoperative chemotherapy treatments. Twenty-six months later no sign of the disease was observed. Association of verapamil and cyclosporine with chemotherapy allowed to get a good clinical response with a very low toxicity, in a critical situation in which chemotherapy alone did not seem to offer any real possibility.

Bone Neoplasms↗
PubMed1995

Fatal pneumopathy in children after bone marrow transplantation--report from the Italian Registry. Italian Association of Pediatric Hematology-Oncology BMT Group.

We have examined data reported in the AIEOP-BMT Registry in order to determine the incidence, causes and risk factors for fatal pneumopathy after bone marrow transplantation in a pediatric population. Overall, in the Registry 1134 children are reported, 531 of whom received an autologous BMT, 468 allomatched BMT, eight syngeneic, 75 mismatched, 29 unrelated and 23 peripheral blood progenitor cells as rescue after myeloablative therapy in the period 1983-1993. 198 patients out of 1134 (17%) died of transplant-related causes and 86 of them died of pulmonary complications: 12 were recorded as fungal pneumonia, eight bacterial, four bacterial and fungal, six viral, two Pneumocystis carinii pneumonia, 12 ARDS, 13 interstitial, 29 unspecified 'respiratory failure'. Multivariate analysis showed that only type of graft and presence or absence of Pneumocystis carinii prophylaxis influence the cumulative incidence of fatal pneumonia. After autologous BMTs only Pneumocystis carinii prophylaxis was significant in multivariate analysis. After allogeneic BMTs multivariate analysis showed that BMT type, Pneumocystis carinii prophylaxis and GVHD grade seem to maintain their influence on cumulative incidence of fatal pneumonia. After BMT the incidence of fatal pneumopathy in children is low (9%), but it represents the second cause of death after primary disease. Pneumocysti carinii prophylaxis should also be given after autologous BMT.

Adolescent↗
PubMed1995

Pre-B acute lymphoblastic leukemia in a patient with partial lipodystrophy and acanthosis nigricans.

In patients with lipodystrophies a post binding defect in insulin action has been described involving phosphorylation of the beta subunit of the insulin receptor, suggesting the presence of a genetically determined defect in insulin action; the receptor gene has been mapped to the distal short arm of chromosome 19 close to the break-point of a specific chromosome translocation frequently found in pre-B Acute Lymphoblastic Leukemia (ALL). We report on a 13 years old female patient with partial lipodystrophy, acanthosis nigricans and insulin resistance who developed a pre-B ALL. Since lipodystrophy and pre-B ALL are rare disorders, a possible causal relationship between the two diseases is suggested possibly mediated by a mutation in the insulin receptor gene.

Acanthosis Nigricans↗
PubMed1995

Usefulness of frequency analysis of cytotoxic T-lymphocytes precursors (CTL-p) for selection of HLA matched unrelated marrow donors.

A child with Sanfilippo syndrome and 5 potential unrelated marrow donors were typed serologically, tested in mixed lymphocyte reaction and typed by restriction fragment length polymorphism analysis in attempt to find a suitable donor. All donors were found to be identical with the recipient, however, these studies were not conclusive in identifying the best match donor. Therefore, recipient-donor pairs were examined by HLA-DR oligotyping. In addition we have studied the potential of cytotoxic T-lymphocytes precursors (CTL-p) analysis as a means of selection for matched unrelated donors. Low frequencies (1/10(5)) of pretransplant CTL-p correlated with oligotyping identity in all donor-recipient pairs evaluated. In one case oligotyping disclosed a previously unrecognized HLA-DRB1 disparity. This resulted in high frequencies of CTL-p (1/35,000). Based on this experience we can argue that CTL-p analysis may be used as an additional tool for selection of compatible unrelated marrow donors.

Bone Marrow Transplantation↗
PubMed1994

Treatment of chronic sporadic-type non-A, non-B hepatitis with lymphoblastoid interferon: gamma GT levels predictive for response.

The aim of this study was to evaluate the efficacy of human lymphoblastoid interferon-alpha treatment in chronic sporadic-type non-A, non-B hepatitis. We also aimed to determine if histological or liver function data could predict either response or relapse. Sixty patients with chronic sporadic-type non-A, non-B hepatitis were randomized in two groups of 30. One group was treated with interferon-alpha (3 MU thrice weekly) for one year; the other group was untreated controls. The treated group was followed for another year after interferon withdrawal. Liver function tests were performed during treatment. Liver biopsy was carried out before and a year after randomization. We evaluated rate of response [normalization of alanine aminotransferase (ALT) levels for at least three consecutive months] and rate of relapse (ALT rebound after therapy suspension). We also looked at possible predictive factors for response and relapse. In the treatment group the rate of response was 55% (16/29). No control patient exhibited ALT normalization. Among the responders, 31% (5/16) relapsed after interferon withdrawal. Low gamma GT and female sex are positive predictive factors of response (P < 0.01 and P < 0.02 respectively). Presence of portal and periportal inflammation at the second liver biopsy was correlated with relapse (P < 0.05). In conclusion, human lymphoblastoid interferon-alpha treatment for one year is beneficial in patients suffering from chronic sporadic-type non-A, non-B hepatitis. Low pretreatment gamma GT levels and female sex are positive predictors of response in this patient population.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Indomethacin enhances serum 2'5'-oligoadenylate synthetase in patients with hepatitis B and C virus chronic active hepatitis.

Activation of the arachidonic acid metabolism seems to be one of the post-receptor mechanisms by which interferon-alpha induces antiviral protein synthesis. In this study, we evaluated the changes on serum 2'5'-oligoadenylate synthetase levels induced by acute administration of interferon-alpha, indomethacin and interferon-alpha plus indomethacin in 21 patients with hepatitis B or C virus chronic active hepatitis. Serum samples for 2'5'-oligoadenylate synthetase determination were collected in basal conditions and 8 h after the administration of interferon-alpha, indomethacin and interferon-alpha plus indomethacin. Compared to control value (mean +/- SE) (40.2 +/- 7.9 pg/dl) serum 2'5'-oligoadenylate synthetase concentration was significantly increased 1.5-fold after interferon-alpha (63.4 +/- 11, p < 0.001), 2.8-fold after indomethacin (115.5 +/- 21, p < 0.001) and 3.7-fold after interferon-alpha plus indomethacin (148.9 +/- 25.1, p < 0.001). When patients with different viral infections were considered separately, basal 2'5'-oligoadenylate synthetase concentrations were similar in both HBeAg- and HBeAb-positive patients, but about 2-fold higher in hepatitis C virus. Compared to the control value, interferon-alpha caused a 1.5-fold increase in HBeAg- and hepatitis C virus-positive and a 2-fold increase in HBeAb-positive patients. Indomethacin led to a 1.8-fold increase in HBeAg, a 2-fold increase in hepatitis C virus-positive and surprisingly a 6.8-fold increase in HBeAb-positive patients. Simultaneous administration of the two drugs had an additive effect on the 2'5'-oligoadenylate synthetase increase in HBeAg-positive (2.4-fold increase) and a synergistic effect in hepatitis C virus- and HBeAb-positive patients (2.7- and 10.2-fold increase, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

2',5'-Oligoadenylate Synthetase↗
PubMed1994

Monitoring of cyclosporine blood levels from central venous lines: a misleading assay?

In order to assess the suspected influence of indwelling lines on the measurement of cyclosporine (CSA) blood levels, we evaluated CSA concentrations in samples drawn simultaneously from both silicone catheter lumens and peripheral veins of eight bone marrow transplant recipients. Blood samples were obtained at 30 min or 6-12 h after discontinuation of intravenous CSA. CSA concentrations were determined in whole blood by specific monoclonal antibody assay. Mean CSA levels from the lumen used for CSA administration were significantly higher than those from samples drawn from the second lumen (i.e., not used for CSA infusion) or peripheral vein. This difference, obtained when the infusion had been interrupted for 30 min, was still the case 6-12 h after discontinuation of CSA infusion. No difference was found between samples obtained from the second lumen and peripheral vein. These observations suggest that CSA might be adsorbed or bound by the silicon catheter and, thus, CSA blood level measurements may be misleading. The second lumen of the catheter or a peripheral vein should be used for accurate monitoring of CSA concentrations.

Adolescent↗
PubMed1994

[Use of cyclosporin and verapamil in association with chemotherapy in the treatment of pediatric patients with advanced-stage neoplasms. A pilot study].

Multidrug resistance represents one of the most important factors that may lead to a therapeutic failure in some patients affected by malignancies. One of the best known mechanisms is linked to the genic amplification or the overproduction of a membrane glycoprotein, GP170, that is the product of the gene MDR1. The existence of drugs (calcium blockers, cyclosporine, tamoxifen, reserpine, quinidine) able to bind themselves to gp170 and to paralyze its activity in vitro is well known. We studied 20 pediatric patients (median age 9 years) affected by acute lymphoblastic leukemia (ALL), osteosarcoma, neuroblastoma and medulloblastoma, in advanced stage of disease. We employed in all cases the association of cytostatics with verapamil (50-70 mg/m2 i.v.) and cyclosporine (5-8 mg/kg i.v.) with different infusion schedules. In leukemias we administered vincristine (1.5 mg/m2), and daunomycin (40 mg/m2), in solid tumors VP16 (150 mg/m2) and adriamycin (60 mg/m2). Seventy-two therapeutic courses were performed: 39 in ALL, 16 in osteosarcoma, 16 in neuroblastoma and 1 in medulloblastoma. On the whole 5 complete remissions were achieved in ALL patients and 1 in an osteosarcoma patient. We did not observe a significant myelosuppression during treatment, therefore few infectious complications occurred; furthermore electrocardiographic changes have been mild and promptly resolved after temporary discontinuation of verapamil infusion. Our data suggest a synergy of verapamil and cyclosporine in the inhibition of multidrug resistance induced by gp170, without the occurrence of heavy toxicity. The results obtained in ALL patients are encouraging., especially in view of a possible subsequent bone marrow transplantation, while in solid tumors they are not as satisfying.

Adolescent↗
PubMed1994

Autologous bone marrow transplantation for childhood acute lymphoblastic leukemia in remission: first choice for isolated extramedullary relapse?

Between May 1984 and May 1992, 75 children 3-19 (median 9) years of age underwent autologous marrow transplant. Clinical data were obtained from the BMT Registry of the AIEOP (Italian Association of Pediatric Hemato/Oncology). Fifty-six children were transplanted after marrow +/- other site(s) relapse and 19 after an isolated extramedullary relapse. The transplant preparative regimens varied according to the center performing the transplant. Seven patients (9%) died of transplant-related complications. Forty-four (58.6%) of 75 patients relapsed again following autologous BMT. The 5-year DFS was 27.8%. An isolated extramedullary relapse was the only variable that statistically influenced DFS. In this retrospective study, autologous BMT for patients with ALL in second CR following marrow relapse did not offer an encouraging result (13% probability of DFS at 5 years), whereas autologous BMT following an (early) isolated extramedullary relapse resulted in nearly 70% DFS. Autologous BMT may be appropriate for this latter group of patients.

Adolescent↗