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F Chimirri

Publications and source records attributed to F Chimirri.

6 recordsLinked to original sources

Predictive testing for Huntington's disease: ten years' experience in two Italian centres.

Pre-symptomatic testing for Huntington's disease (HD) has been available as a clinical service in the medical centres of Rome and Genoa since December 1987, initially by DNA-linkage and since mid-1993 by direct mutation analysis. A multidisciplinary approach and a protocol which follows the Ethical Issue Policy Statement on Huntington's Disease Molecular Genetics Predictive Test has been used. In the period under study, 332 subjects requested the test, 288 were enrolled in the protocol and nearly half of these completed it. One hundred and forty-eight people withdrew from the testing procedure for various reasons but most frequently due to a more realistic evaluation of all possible consequences of test results, induced by psychological counselling. Therefore, 140 people completed the test. The overall gene-carrier/non-carrier ratio was 0.46:1. None of the identified gene carriers had catastrophic reactions such as suicide, suicide attempts or major psychiatric disorders. All appear to have had a similar pattern of reactions to an adverse result and none expressed regret for undergoing the test. In conclusion, presymptomatic testing for HD can be considered a safe procedure without adverse consequences when framed in an integrated protocol at qualified genetic centres.

Adaptation, Psychological↗

Mobilization and transplantation of Philadelphia-negative peripheral-blood progenitor cells early in chronic myelogenous leukemia.

PURPOSE: Mobilization of Philadelphia (Ph) chromosome-negative progenitors is now possible in many Ph1-positive chronic myelogenous leukemia (CML) patients who had received interferon alfa (IFN-alpha) with no cytogenetic response. In this pilot study, we used this approach in patients without prior IFN-alpha therapy to determine if the number and quality of mobilized progenitors would be increased and to evaluate the potential effect of these cells as autografts. PATIENTS AND METHODS: Twenty-two untreated patients were mobilized within 12 months of diagnosis. The treatment regimen consisted of the mini-ICE protocol. Beginning on day +8, granulocyte colony-stimulating factor (G-CSF) was used in all patients. Leukophoresis was performed as the patients were recovering from aplasia, when WBC count exceeded 0.8 x 10(9)/L. RESULTS: In 14 patients, (63%) the leukophoresis product was entirely Ph1-negative and in four patients the Ph1-positive cell rate was < or = 7%. Significant numbers of long-term culture-initiating cells (LTC-IC) and CD34+ Thy1+Lin- cells were found in most of the Ph1-negative collections that were tested. Twelve patients underwent autografting with their mobilized peripheral-blood progenitor cells (PBPC) (Ph1-negative collections, 10 patients; major cytogenetic response, two patients). All patients engrafted and are alive; six have Ph1-negative marrow 7 to 15 months after autografting. Posttransplant treatment was IFN-alpha combined with interleukin (IL)-2 because of the recent demonstration of synergistic activity in augmenting cytolytic activity. CONCLUSION: Intensive chemotherapy given in early chronic phase of CML is well tolerated and results in high numbers of circulating Ph1-negative precursor cells.

Adult↗

High-dose chemo-radiotherapy followed by autologous Philadelphia chromosome-negative blood progenitor cell transplantation in patients with chronic myelogenous leukemia.

Twenty-three patients with chronic myelogenous leukemia in early chronic phase (ECP) and not previously treated with alpha-interferon (IFN-alpha) (10 patients), in ECP but pretreated with IFN-alpha (<12 months) (seven patients) and in late chronic phase (LCP) pretreated with IFN-alpha (>12 months) (six patients) underwent autografting with Philadelphia (Ph) chromosome-negative blood progenitor cells (BPCs) (20 patients), or partially/totally Ph-positive BPCs (three patients), previously mobilized during the early phase of recovery after aplasia induced by intensive chemotherapy. The conditioning regimen consisted of high-dose chemotherapy alone or followed by total body irradiation (TBI). Recombinant G-CSF was given after BPCs infusion on day +8. All patients in ECP not pretreated with IFN-alpha are alive and five of them are Ph-negative in the marrow after autografting. Six of seven patients autografted with Ph-negative BPCs in the group of ECP pretreated with IFN-alpha (<12 months) are alive and two of them are still Ph-negative in the marrow. In the same group, the only patient transplanted with partially Ph-positive BPCs, died of blastic transformation 2 months after reinfusion. Three patients (two patients autografted with Ph-negative BPCs and one patient with Ph-positive BPC) in the group of LCP pretreated with IFN-alpha >12 months are alive but Ph-positive after autografting. The other three patients of the same group died of procedure-related toxicity (two patients) and blastic transformation (one patient). Seventeen patients (10/10 ECP not pretreated with IFN-alpha; 5/7 ECP pretreated with IFN-alpha and 2/6 LCP pretreated with IFN-alpha) of 23 autografted patients were treated with IFN-alpha +/- IL-2. Toxicities after autografting were mostly related to myelosuppression, particularly thrombocytopenia. All patients of the two groups pretreated with IFN-alpha developed febrile episodes during the aplastic phase following BPCs reinfusion. No patient autografted in ECP and those not pretreated with IFN-alpha developed febrile episodes. This is also probably due to the use of i.v. antibiotic and antimicotic prophylaxis when neutrophils were < or = 1 x 10(9)/l after autografting. Greater toxicity was observed in patients pretreated with IFN-alpha, being lethal in two cases in LCF. In conclusion, the "in vivo' manipulation approach employed in our institution is a safe procedure and it results in a high collection of Ph-negative cells in the blood if the cells are harvested: (1) in early chronic phase; (2) in early phase of recovery after chemotherapy-inducing aplasia; (3) in patients not extensively pretreated with IFN-alpha. The data presented here have shown encouraging trends in chronic phase of CML and offer new perspective for patients without an HLA-identical donor or for patients who do not respond to IFN-alpha.

Adult↗

In vivo mobilization of karyotypically normal peripheral blood progenitor cells in high-risk MDS, secondary or therapy-related acute myelogenous leukaemia.

We have previously reported that mobilization of Philadelphia (Ph) chromosome-negative progenitors is possible in a significant number of Ph1-positive acute lymphoblastic leukaemia (ALL) and chronic myelogenous leukaemia (CML) patients. In this pilot study we employed the same approach for patients with RAEB-t, secondary AML (sAML) and therapy-related AML (t-AML). All patients except one had double or complex cytogenetic abnormalities in marrow cells before mobilization therapy. All patients received an idarubicin-containing regimen (mini-ICE protocol) followed by rh-G-CSF and the first leukapheresis was performed as they were recovering from aplasia. In six out of nine patients the leukapheresis product was entirely karyotypically normal, combined with a significant number of CFU-GM. CD34+ cells and LTC-IC. Recovery time from mobilization therapy was short and no patient died as a result of the procedure. To date, three patients have undergone autografting using their karyotypically normal collections, of which two (sAML) are alive with karyotypically normal marrow a few months after autografting.

Adult↗

[Hairy-cell leukemia].

This is a review of current opinions on all aspects of diagnosis and treatment of hairy-cell leukemia. First, the authors report a concise but complete description of clinical and hematological characteristics of the disease with particular attention to peripheral blood and bone marrow morphological, cytochemical and cytogenetic features. Still concerning the diagnostic phase, the authors report a brief description of splenic, hepatic and lymph nodal histological pictures and some informations about immunophenotypic diagnosis with monoclonal antibodies. A space is then given to differential diagnosis and prognostic factors which have remarkably changed over the years. The second part of this review concerns current treatments for hairy-cell leukemia and analyses all the aspects of the different therapeutic strategies. Data, for this analysis were obtained from the Italian Cooperative Group's Studies and from other published series. Special attention was given to the impact of splenectomy, alpha-interferon therapy and new drugs such as purine analogues (2-CdA, 2-dCF) on the management of the disease. The last section concerns minimal residual disease, second neoplasia and the most common causes of death. A whole paragraph is dedicated to hairy-cell leukemia variants.

Biopsy, Needle↗