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Biomedical subjects

G Rosti

Publications and source records attributed to G Rosti.

At least 109 records · Page 6Linked to original sources
PubMed1993

Hypercoagulability in patients undergoing autologous or allogeneic BMT for hematological malignancies.

Severe thrombotic alterations, such as veno-occlusive disease of the liver, may occur in the early phase following high-dose chemoradiotherapy and BMT. In this study, performed in patients with hematological malignancies subjected to allogeneic (10 cases) and autologous (20 cases) BMT, we have monitored laboratory hemostatic parameters to better understand the pathogenetic mechanism of thrombosis and particularly of veno-occlusive disease. Prothrombin time, activated partial thromboplastin time, plasma fibrinogen, markers of hypercoagulability (thrombin-antithrombin complex and prothrombin fragment F1+2); natural anticoagulants (protein C, protein S and antithrombin) together with fibrinolytic parameters (plasminogen, alpha 2-antiplasmin, tissue-plasminogen activator, plasminogen activator inhibitor and D-dimer) were assessed before transplant, on day 0 and weekly for 1 month thereafter. A hypercoagulability state, not related to an impairment of the anticoagulant and fibrinolytic systems, was documented before and after autologous and allogeneic transplant. Two patients developed veno-occlusive disease: they did not show any difference from the other patients before transplant while they presented a decrease of the natural anticoagulants along with altered fibrinolytic parameters only at the clinical onset of veno-occlusive disease. In conclusion, in this study a state of marked hypercoagulability was documented in BMT patients and the hemostatic laboratory parameters evaluated were not able to predict the occurrence of the thrombotic complications.

Antithrombin III↗
PubMed1993

In vitro amplification of hypervariable DNA regions for the evaluation of chimerism after allogeneic BMT.

The role of mixed hematopoietic chimerism in engraftment and relapse after allogeneic BMT remains unclear. To better evaluate post-transplant chimerism we used polymerase chain reaction (PCR) in vitro amplification of four single locus simple repetitive DNA sequences, all of which vary extensively in their repeat number among different individuals: variable number of tandem repeats D1S80, APOB and D17S5, and the tetranucleotide repeat F8VWF. We tested 13 cases of CML, four of multiple myeloma (MM), three of ANLL and one of B-CLL. In a sequential analysis protocol with the different loci, the donor could be distinguished from the recipient in 14 of 20 (70%) pairs with the first marker used (D1S80). When a donor of opposite sex was involved, karyotyping and Y chromosome-specific PCR were also used. With the use of the four markers, chimerism was identified in all the pairs. Mixed chimerism was present in 5 patients, and complete chimerism in 15. No patients relapsed. The application of PCR for documenting post-transplant chimerism has several advantages over Southern blotting: increased sensitivity, use of small amounts of sample, ease of preparation of DNA, elimination of restriction enzyme analysis and of radioisotopes, and speed.

Adult↗
PubMed1993

New strategies for selection of unrelated bone marrow donors.

An important problem in the selection of unrelated donors for bone marrow transplantation (UD-BMT), is HLA matching, between selected donor and recipient. Serological screening, mixed lymphocyte culture (MLC), and sequence specific oligonucleotide genotyping (PCR-SSO) are the methods commonly used for typing of HLA-genes. These ways to select donor candidates are time-expensive. We set up new applications of the "fingerprinting-PCR" technique, to analyse the polymorphic second exon of DRB, DQB, DQA, DPB of HLA Class II and second exon A, B, C HLA-Class I genes, and to search for identity between patient and serologically selected unrelated donors. In an assessment of the technique, 50 normal samples, and 4 unrelated HLA-A and HLA-B serological matched patient-donor pairs were analysed for HLA polymorphic regions. In 3 of the 4 cases (UD-BMT) at least HLA-DRB mismatched different donor-transplanted patterns were identified. In all cases PCR-SSO analysis was performed as control. Based on our data, we suggest that identification of UD for allogeneic BMT should follow these steps: 1) serological HLA-Class I and II genes screening; 2) HLA-Class II DRB gene PCR fingerprinting; 3) confirmation by SSO analysis in case of fingerprinting identity. 4) HLA-Class II DQA, DQB, DPB PCR fingerprinting. Moreover, confirmation by PCR fingerprinting or protein isoelectrofocusing of HLA-Class I identity is recommended. This "strategy" may contribute to rapid and specific selection of unrelated marrow donors.

Base Sequence↗
PubMed1992

High-dose chemotherapy supported with autologous bone marrow transplantation (ABMT) in germ cell tumors: a phase two study.

In this paper, the first Italian multicentre experience with high-dose chemotherapy and ABMT in germ cell cancer is presented. Twenty-eight patients underwent treatment with a carboplatin-etoposide w/o ifosfamide high-dose combination. Seventeen patients were in progression of disease, 9 were responsive to salvage treatments or failed to achieve CR to front line, and 2 had stable disease (both with an elevated marker level) at the time of transplantation. Five patients, all of whom were in sensitive relapse at transplantation, are alive and disease-free at > 17 months' follow-up. Two patients died 15 days after ABMT, one of veno-occlusive disease and one of rapid uncontrolled tumor progression. In highly pretreated patients this schedule seems to provide an option of cure for a cohort of patients failing to achieve CR to standard salvage regimens for germ cell cancer. Definitive conclusions may eventually be drawn with a more homogeneous group of patients. This type of approach should continue to be taken in sensitive relapse patients only, as responses in progressive cases are very transient, with virtually no cures. The question of whether high-dose programs are better than standard chemotherapy will in any case be answered only in a randomized prospective trial.

Adolescent↗
PubMed1992

An Italian experience of high-dose chemotherapy and autologous bone marrow transplantation (ABMT) in germ cell tumours. Suggestions for future direction.

In this paper an Italian cooperative trial investigates the role of a high-dose regimen with carboplatin, etoposide and ifosfamide in germ cell tumours. Twenty-eight patients underwent one or two transplants. Seventeen with progressive disease. Nine in sensitive relapse and two with stable disease after salvage therapy. Toxicity was generally moderate: two deaths occurred at day 15 from ABMT (one from VOD and one from tumour growth). Five patients are alive and disease free at least 10 months follow-up. In highly pre-treated patients this high-dose combination seems to give an option of cure for relapsed patients. Early transplantation is suggested.

Adolescent↗
PubMed1992

Dose-intensive therapy for germ cell neoplasms.

Dose-intensive chemotherapy for recurrent or refractory germ cell cancer has evolved over the last decade. Initial experience using high-dose regimens including single agents like cyclophosphamide, thiotepa, and etoposide demonstrated that responses could be obtained in the majority of patients but that they tended to be of short duration. Second-generation studies focusing on this disease site incorporated drugs and principles specific to germ cell cancer. Large studies performed at Indiana University (Indianapolis, IN) and in several European centers have demonstrated that the addition of high-dose carboplatin or cisplatin to other regimens can result in long-term survival of otherwise incurable patients. With the results of initial pilot studies now confirmed, high-dose carboplatin-based chemotherapy is beginning to play a role in first salvage therapy, and in some centers is being used in protocols of initial therapy for poor-risk patients. Based on the success of some of the early studies in germ cell cancer, similar protocols also are being investigated for other disease sites such as ovarian cancer, neuroblastoma, lymphoma, and breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Minimal residual disease status in transplanted chronic myelogenous leukemia patients: low incidence of polymerase chain reaction positive cases among 48 long disease-free subjects who received unmanipulated allogeneic bone marrow transplants.

Forty-eight long-term disease-free chronic myelogenous leukemia (CML) patients, who had received unmanipulated allogeneic bone marrow transplants (BMT) for eradication of the Philadelphia (Ph1)-positive clone were studied by polymerase chain reaction (PCR), using a very sensitive PCR procedure and very stringent criteria for preventing and revealing contamination. Nine patients (18%) were positive at the first PCR examination, but only one patient remained PCR positive four years after. However, a second PCR analysis performed on new bone marrow samples obtained at a median interval of 14 months (range 6-16) after the first specimen collection from six of nine originally positive cases, and from 16 of 39 originally negative cases, showed that only one of the six positive cases remained positive, whereas negativity was confirmed in all the originally negative patients. These data are evidence that the Ph1-positive clone is apparently completely eradicated in the majority of CML patients who survive disease-free long-term after an unmanipulated allogeneic BMT and that only sporadic cases remain PCR-positive four years post-BMT. The data also show that at least two sequential bone marrow samples for each patient must be analyzed before drawing conclusions regarding the stable persistence of BCR/ABL transcripts and the minimal residual disease status.

Adolescent↗
PubMed1991

Primary lymphoma of the central nervous system.

Primary lymphoma of the central nervous system (CNS) represents a pathology that is no longer considered rare, also in the light of its high correlation with the human immunodeficiency virus (HIV) syndrome reported recently. Often the correct diagnosis of the disease is difficult to reach, owing to the wide spectrum of non-lymphoma pathologies from which it should be differentiated and the invasiveness of some diagnostic techniques. The biologic aggressiveness of the neoplasm often makes a combined radio-chemotherapeutic approach necessary. In contrast, surgical resection does not seem to provide any significant benefit. The clinical experience reported here, together with a review of the most recent literature, lead the authors to suggest the opportunity of treating primary lymphoma of the CNS with the most active and modern chemotherapeutic protocols in association with traditional treatments to obtain an improvement in overall survival.

Aged↗
PubMed1991

Cytogenetic events after bone marrow transplantation for Philadelphia chromosome positive chronic myeloid leukemia.

Allogeneic bone marrow transplantation is the only way to cure patients with Ph1+ chronic myeloid leukemia. It is commonly assumed that, in order to obtain a cure for the patients, the leukemic clone must be completely destroyed by the conditioning treatment and the donor's bone marrow must repopulate the hemopoietic niches leading to a "complete chimera". However, cytogenetic analyses, supported by molecular ones, indicate that Ph1+ cells, far from being completely destroyed by chemo-radiotherapy may persist for a long time, probably in the majority of the patients. As demonstrated by the outcome of patients receiving T-cell depleted marrow, immune mechanisms must be involved in controlling and progressively reducing the size of the residual leukemic clone. Furthermore, immunodulating therapeutic strategies, represented by cyclosporin-A discontinuation or alpha interferon treatment, may successfully reduce the Ph1+ cell population even after a full relapse.

Bone Marrow Transplantation↗
PubMed1991

Long-term outcome of adults with acute myelogenous leukaemia: results of a prospective, randomized study of chemotherapy with a minimal follow-up of 7 years.

In a prospective study running between 1981 and 1983, a group of 156 adult (under 60 years of age) patients with de-novo acute myelogenous leukaemia were randomly assigned to receive a daunorubicin, cytosine arabinoside and thioguanine combination or a regimen containing lower dosages of these drugs but also containing etoposide and vindesine. Patients who entered complete remission received maintenance therapy for 2 years. The survival and remission duration curves of the two groups were exactly superimposable and for this long-term analysis all patients have been considered together. The follow-up times range between 84 and 104 months. Actual survival at 7 years is 15% (95% confidence intervals 9-20%), with a stable curve thereafter. Actual probability of continuous complete remission at 7 years is 22% (95% C.I. 13-31%) with a stable curve beyond that point. These findings, similar to those of the few other studies of chemotherapy with comparable follow-up times, suggest that only a small fraction of adult patients become long-term survivors, irrespective of the precise type or amount of antineoplastic agents administered.

Adolescent↗
PubMed1991

High dose chemotherapy with carboplatin, VP 16 +/- ifosfamide in germ cell tumors: the Italian experience.

This schedule has shown an interesting activity with nearly 40% of the patients achieving CR. Moreover 4 patients experienced an inversion rate (CR with ABMT when they never achieved this status before). In terms of toxicity, this schedule seems feasible with 2/28 toxic deaths, which is in the lower part of the range of major solid tumors ABMT programs. But even if the rationale is proper, a better patients' selection is required. The CCR (continuous Complete Remission) rate is overimposable to other main studies previously published, but all our CCR were obtained in responding patients (Sensitive Relapses or unresectable PR). We may suggest that earlier transplantation is advisable when less tumor bulky is present and less clonal eterogeneity. The exact maximum tolerated dose of Carboplatin/VP 16/Ifosfamide programs has not yet clearly pointed out. The lack of major life-threatening episodes and neuro/nephrotoxicity may allow us to explore higher Carboplatin doses. Anyway the ultimate answer to the utility of ABMT trials must come from a randomized study in responding patients.

Adult↗
PubMed1991

Bone marrow transplantation for chronic lymphocytic leukemia.

The classic treatment of chronic lymphocytic leukemia (CLL) aims at prolonging survival, without attempting to eradicate the disease. CLL commonly affects the elderly, but a small proportion of patients are less than 50 years old. In this age group a novel form of therapy, high-dose chemoradiotherapy and allogeneic bone marrow transplantation (BMT), has been used recently. Review of the literature and the IBMTR data show that 26 patients have received BMT (24 allogeneic, two syngeneic). Patients were predominantly male (20/26) with an age ranging between 21 and 49 years; 18 had advanced disease at BMT and had received multiple courses of chemotherapy to which they were considered refractory. Conditioning consisted of cyclophosphamide and fractionated total body irradiation, plus additional agents in one-third of the patients. Graft-versus-host disease (GVHD) prevention was variable. Twenty-five patients are evaluable: 12 died of early complication of BMT (GVHD, infection, haemorrhage, etc.) and only two died of CLL. The effect of BMT on the disease was evaluable in 22 patients: 19 achieved a remission, three showed persistent disease and two relapsed; 11 were alive and apparently disease-free, with follow-up between 5 and 48 months. In two of these patients molecular biology studies showed no residual disease. These results indicate that further studies of the use of BMT for selected patients with CLL appear to be justified.

Adult↗