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Biomedical subjects

G Meloni

Publications and source records attributed to G Meloni.

At least 145 records · Page 8Linked to original sources

Therapy-induced Ph1 suppression in chronic myeloid leukemia: molecular and cytogenetic studies in patients treated with alpha-2b IFN, high-dose chemotherapy and autologous stem cell infusion.

In this study, cytogenetic and molecular analyses were employed to assess the response to therapy in 29 chronic myeloid leukemia patients undergoing high dose chemotherapy followed by autologous stem cell infusion. Of these, 11 had previously achieved hematologic remission and cytogenetic improvement after alpha-2b interferon (IFN) treatment, whereas 18 underwent autografting in an early phase of the disease. In each case bone marrow samples were examined pre-treatment and at +2, +6 and +12 months in order to verify the degree of Ph1 suppression. In addition, the position of the breakpoint within the BCR region was mapped with multiple restriction enzymes. In 17 cases (59%) a significant Ph1 reduction was observed at +60 days (0-57% residual Ph1+ cells). In three of these cases, a complete cytogenetic response was confirmed at the DNA level by Southern blotting, but specific amplification of the BCR/ABL junction by the polymerase chain reaction (PCR), performed in two cases, still showed residual disease. The remaining 12 patients (41%) revealed a substantial persistence of Ph1+ metaphases (90-100%). Nine of 17 responding patients (53%) showed an increase of Ph1+ cells at 6 months, and five of 20 evaluated had a further increase at 12 months. With the exception of the results seen by PCR, comparison of molecular and cytogenetic techniques did not show significant differences. The variable degrees of Ph1 suppression observed did not appear to be associated with the position of BCR breakpoints. The factors predicting cytogenetic response to IFN and stem cell autograft and long-term durability of cytoconversion should be elucidated in further studies and with longer follow-up.

Base Sequence↗

Autologous bone marrow transplantation in patients with AML in first complete remission. Results of two different conditioning regimens after the same induction and consolidation therapy.

Thirty-nine patients with acute myeloblastic leukemia (AML) in first complete remission (CR) were treated by autologous bone marrow transplantation. All patients received the same induction and consolidation chemotherapy consisting of a combination of daunorubicin (DNR) and cytarabine (Ara-C) followed by four courses of DNR, Ara-C and 6-thioguanine (6-TG). Two different conditioning regimens were used; 25 patients were submitted to the BAVC regimen (BCNU, amsacrine, VP-16 (etoposide) and Ara-C) and 14 to a cyclophosphamide/total body irradiation (CY + TBI) regimen. Six patients (one treated with BAVC and five treated with CY + TBI) died in aplasia. Twelve of the 25 BAVC treated patients and one of the nine CY + TBI treated patients relapsed; 12 (48%) of the BAVC treated patients are in CR with a median follow-up of 45 months and eight (57%) of the CY + TBI treated patients are in CR with a median follow-up of 50 months. All patients in CR have survived for more than 2 years since transplant.

Adolescent↗

Immunoreactive beta-endorphin levels in cerebrospinal fluid of children with acute lymphoblastic leukemia: relationship with glucocorticoid therapy and neurological complications.

Neurological disorders, such as seizures, are not infrequently associated with anti-leukemic therapy. It has been hypothesized that a disrupted peptidergic transmission between neurons could be the cellular basis of the neurological dysfunction. Since endogenous opioids have been recently found to alter neuronal function and possess anticonvulsant properties, the cerebrospinal fluid (CSF) immunoreactive beta-endorphin levels in children with Acute Lymphoblastic Leukemia (ALL) during chemotherapy and cranial irradiation have been studied. Twenty-seven children, 2 at low, 20 at medium and 5 with high risk ALL, undergoing prophylactic treatment for meningeal leukemia, entered the study. Sequential lumbar punctures with introduction of MTX combined with oral prednisone therapy were performed; each lumbar puncture sample was collected and assayed for immunoreactive beta-endorphin. All the patients studied showed a biphasic profile of the peptide with the minimum levels reached during the induction (days 14-28) and the maximum levels detected at the end of the intensification chemotherapy (days 49-55). In the 3 groups the beta-endorphin decrease corresponded to the period of prednisone therapy; the increase was concomitant with the suspension of oral glucocorticoids. 3 patients showed tonic-clonic seizures which coincided with the lowest cerebrospinal fluid beta-endorphin levels and, in the follow-up, 13 out of 27 patients displayed EEG abnormalities. From these findings a relationship between cerebrospinal fluid beta-endorphin concentrations and neuronal excitability in patients with ALL can be suggested. It is also evidenced that oral glucocorticoid therapy has profound inhibitory effects on central beta-endorphin levels.

Adolescent↗

Acute myelogenous leukemia in first relapse treated with two consecutive autologous bone marrow transplantations: a pilot study.

The feasibility and the antileukemic activity of a double sequential autograft has been evaluated in 3 patients affected by AML in first hematological relapse. Bone marrow collection and cryopreservation was performed twice: during first complete remission (CR) and during second CR. At the time of relapse patients underwent first ABMT with BAVC preparative regimen achieving a second CR without any remarkable complications. After 4, 5 and 4 months respectively a second ABMT was performed with a different preparative regimen, consisting of cyclophosphamide and fractionated total body irradiation (Cy + F-TBI). A delay in platelet recovery was observed after the second procedure as compared to the first, while neutrophils recovery was comparable. 1 patient died in CR (on day +91 after second ABMT) of interstitial pneumonitis. 2 patients are alive and well without evidence of disease after 46 and 53 months of unmaintained second CR. This experience shows the high antileukemic potential of treatment with a double sequential autograft; 2 relapsed patients in fact are long-term survivors with a second CR longer than the first.

Adult↗

Autologous bone marrow or peripheral blood stem cell transplantation for patients with chronic myelogenous leukaemia in chronic phase.

The progressive and fatal course of chronic myelogenous leukemia has not been affected significantly by chemotherapeutic agents that control the benign phase of the disease. Combination chemotherapy and aggressive treatments may offer some advantages: however, these approaches do not appear to produce stable suppression of Ph1 chromosome or to prolong chronic phase and survival of these patients. Only allogeneic bone marrow transplantation has been demonstrated to be capable of inducing a stable, complete suppression of Ph1+ cells. Recently alpha Interferons (IFN) have been shown to control myeloid proliferation in patients with CML and to determine a progressive and persistent decline of Ph1+ bone marrow cells in some cases. The hypothesis that in most newly diagnosed patients with CML various amount of Ph1 negative cells must still be present, albeit in suppressed state in the bone marrow (BM) or in the peripheral blood (PB), have led some Authors to treat patients with high-dose chemotherapy followed by reinfusion of stem cells collected at diagnosis or after a response to cytoreductive treatments. We report 34 patients with CML treated in chronic phase with Busulohan and Melphalan conditioning regimen followed by reinfusion of BM or PB stem cells.

Adult↗

Monoclonal antibody purging and autologous bone marrow transplantation in acute myelogenous leukemia in complete remission.

A mouse monoclonal antibody (S4-7) reacting with human myelomonocytic cells has been previously shown to be suitable for bone marrow purging in selected acute myelogenous leukemia (AML) patients with S4-7 positive leukemic clonogenic cells at diagnosis. The results obtained in seven AML patients who underwent such a treatment, followed by autologous bone marrow transplantation (ABMT), are now reported. Six patients underwent ABMT in first complete remission (CR), one in second CR, after BAVC conditioning regimen. One patient died of infection 1 month after ABMT; in the other six a complete recovery of hemopoiesis was observed. In spite of S4-7 reactivity with normal myelomonocytic cells, a prompt recovery of granulopoiesis was however observed both in in vitro liquid culture and in vivo with a median time of 20 days to reach granulocyte values of 500 x 10(6)/l. The patient transplanted in 2nd CR relapsed 3 months after ABMT. Of the five evaluable patients transplanted in 1st CR, two relapsed 8 and 9 months post-ABMT while three remain in continuous CR at 35, 47, 57 months. Leukemic cells of two of the three patients with recurrent disease were studied at relapse and in both could be detected a significant percentage of S4-7 negative cells, detectable neither at diagnosis nor (one patient) at the time of first relapse after standard chemotherapy.

Antibodies, Monoclonal↗

Phase II trial of intermediate dose ARA-C (IDAC) with sequential mitoxantrone (MITOX) in acute myelogenous leukemia.

Forty-seven patients with primary refractory, relapsed, and previously untreated, poor risk AML were entered into a phase II study of intermediate dose ARA-C (IDAC) (1 g/m2 i.v. over 6 hr, daily for 6 days) with sequential mitoxantrone (MITOX) (6 mg/m2 i.v. bolus 3 hr after the end of each ARA-C infusion). Overall, complete remission was induced in 31 patients (66%), and 1 additional patient entered a partial remission. Seven patients (15%) died of infection during marrow hypoplasia. Response to IDAC + MITOX was influenced by sensitivity to previous therapy: patients with primary refractory and early relapse AML responded less well to the regimen (CR rate 28% and 33%, respectively), as compared to those with previously untreated (CR rate 64%) or late relapse disease (CR rate 85%). Sixteen patients continue in CR at 1-12+ months. Except for the expected severe myelosuppression, the regimen was well tolerated with minimal extramedullary toxicity. The data indicate that the sequential combination of IDAC and MITOX is an effective and tolerable regimen for AML. Consideration should be given to applying this program at earlier stages of AML therapy.

Cytarabine↗

High-dose chemotherapy with autologous bone marrow transplantation in 50 advanced resistant Hodgkin's disease patients: an Italian study group report.

Fifty patients with recurrent Hodgkin's disease have been treated with high-dose therapy followed by autologous bone marrow transplantation. Forty-one patients had extranodal sites of relapse and 31 patients had constitutional symptoms. Two patients had been treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), lomustine, vinblastine, procarbazine, and prednisone (CcVPP), and radiation; 16 patients with MOPP, doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), radiation, and lomustine, etoposide, and prednisone (CEP); 20 patients with alternating MOPP/ABVD, and 12 patients with alternating MOPP/ABVD followed by CEP and radiation. Eighteen patients had progressive disease during alternating MOPP/ABVD protocol alone or during conventional salvage therapy; 32 patients had had a complete remission with first-line therapy but later relapsed, 25 of them having received conventional salvage therapy; 12 achieved no response or progression ("resistant-relapse" patients); and 13 responded partially or completely ("sensitive-relapse" patients). Complete remission occurred in 24 patients (48%) with a median duration of 24 months and 16 patients (32%) achieved partial response with a median duration of 9 months, for an overall response rate of 80%. Ten patients failed to respond and died in progressive disease 1 to 10 months (median, 6 months) after transplantation. Toxicity was significant including infections (20%), liver enzymes and alkaline phosphatase elevations (100%), and carmustine lung toxicity (7%). There were two treatment-related deaths; one patient died of Pseudomonas aeruginosa septicemia and another patient died of cerebral hemorrhage. These results validate the procedure of high-dose therapy followed by autologous bone marrow transplantation in inducing remission in these advanced, highly-treated patients. Clearly, the question of whether high-dose therapy and transplantation will eventually supersede new conventional salvage therapies will be addressed after controlled clinical studies.

Adult↗

[Hydatid localization in the proximal tract of the right branch of the pulmonary artery. Description of a case].

Hydatid localization in the major branches of the pulmonary circulation have rarely been reported. The AA. describe the case of a young male patient, previously operated for pulmonary and hepatic hydatidosis, who was unresponsive to medical treatment and died of right heart failure. At necropsy a large hydatid cyst occluding the right proximal branch of the artery was found.

Adult↗