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Biomedical subjects

Mario Petrini

Publications and source records attributed to Mario Petrini.

At least 19 recordsLinked to original sources

Progressive multifocal leukoencephalopathy in a haploidentical stem cell transplant recipient: a clinical, neuroradiological and virological response after treatment with risperidone.

JC virus (JCV) is a double-stranded DNA virus belonging to family Polyomaviridae. It causes progressive multifocal leukoencephalopathy (PML), mainly in immunosuppressed people. JCV had been shown to require the serotonin 2A receptor for host cell entry. We report a case of clinical, neuroradiological and virological response of biopsy-proven PML in a 33-year-old comatose woman after treatment with the anti-psychotic drug risperidone. Since risperidone is the tightest binding of current drugs to this receptor we think this may have blocked JCV entry in our patient, allowing her immune recovery and viral clearance.

Adult↗

Actin polymerization in neutrophils from donors of peripheral blood stem cells: divergent effects of glycosylated and nonglycosylated recombinant human granulocyte colony-stimulating factor.

Neutrophil functions can be modified by Recombinant human G-CSF (rhG-CSF) treatment, with divergent effects on phagocytosis, motility, bactericidal activity, and surface molecule expression. Neutrophil morphology is modified by treatment with filgrastim (the nonglycosylated form of rhG-CSF), while it is not affected by lenograstim (the glycosylated type of rhG-CSF). Little information is available about actin polymerization in neutrophils from subjects treated with the two types of rhG-CSF. In the current paper we evaluated two groups of donors of peripheral blood stem cells (PBSC) for allogeneic transplantation. Ten subjects were treated with filgrastim and 10 with lenograstim to mobilize PBSC; 15 blood donors were evaluated as a control group. Actin polymerization (both spontaneous and fMLP-stimulated) was studied by a flow cytometric assay. A microscopic fluorescent assay was also carried out to evaluate F-actin distribution in neutrophils. We found that filgrastim induced an increased F-actin content in resting neutrophils, along with morphologic evidence for increased actin polymerization distributed principally at the cell membrane and frequently polarized in focal areas; in addition, fMLP was not able to induce further actin polymerization. On the contrary, treatment with lenograstim was associated with F-actin content, distribution, and polymerization kinetics indistinguishable from those displayed by control neutrophils. Such experimental results show that filgrastim and lenograstim display divergent effects also on neutrophil actin polymerization and provide further explanation for previous experimental findings.

Actins↗

Different gamma/delta T clones sustain GVM and GVH effects in multiple myeloma patients after non-myeloablative transplantation.

TCR gamma/delta profiles were analyzed in 13 multiple myeloma patients after allogeneic non-myeloablative transplantation. Results show that both aGVHD and minimal residual disease (MRD) eradication did significantly affect TCR gamma/delta profile. During follow-up, six patients developed an aGVHD episode; in five of them, this event fitted with a modification of the TCR profile. Eleven patients achieved PCR-negativity during follow-up. In the 90% of them, the appearance of a new predominant TCR peak was concomitant to the disappearance of the IgH clone. These results suggest that different T gamma/delta populations would sustain GVM and GVH effects after non-myeloablative allogeneic transplant.

Adult↗

Effect of epirubicin-based chemotherapy and dexrazoxane supplementation on QT dispersion in non-Hodgkin lymphoma patients.

BACKGROUND AND OBJECTIVE: Aim of the present study was to assess the effect of epirubicin-based chemotherapy on QT interval dispersion in patients with aggressive non-Hodgkin lymphoma (NHL), and the effect of dexrazoxane supplementation. Prolongation of QT dispersion may not only represent a sensitive tool in identifying the first sign of anthracycline-induced cardiotoxicity, but it may serve also in identifying patients who are at risk of arrhythmic events. METHODS: Twenty untreated patients, <or=60 years of age with newly-diagnosed aggressive NHL, eligible for a treatment with epirubicin-based chemotherapy were selected for the study. The patients were randomly allocated in two subgroups (N=10) to receive or not dexrazoxane hydrochloride (400 mg/m(2)) after epirubicin infusion. The patients underwent 12-lead electrocardiogram (ECG) before and after epirubicin infusion and after dexrazoxane supplementation. QT dispersion was defined as the difference between the maximum and the minimum QT interval occurring in any of the 12 ECG leads, corrected (QTc) for heart rate. RESULTS: All the 20 patients showed increased QT dispersion (44.3 +/- 8.4 vs. 68.4+/-11.4 ms, P<0.001) and QTc dispersion (46.2 +/- 6.2 vs. 72.2 +/- 8.4, P<0.001) after chemotherapy infusion. The 10 patients who underwent supplementation with dexrazoxane exhibited a significant reduction of QT dispersion (67.4 +/- 8.1 vs. 49.5 +/- 4.2 ms, P<0.001) and QTc dispersion (71.2 +/- .7 vs. 51.4 +/- 4.3 ms, P<0.001), while the 10 patients not supplemented with dexrazoxane did not (QT dispersion: 69.3 +/- 7.6 vs. 64.2 +/- 6.9 ms; QTc dispersion: 72.8 +/- 8.1 vs. 67.3 +/- 7.2 ms, ns). CONCLUSIONS: Epirubicin-based chemotherapy causes an early increase of the QT and QTc dispersion, which is attenuated by dexrazoxane supplementation. Therefore, dexrazoxane can reduce the arrhythmic risk in patients treated with epirubicin.

Antibiotics, Antineoplastic↗

Quantitative molecular monitoring of BCR-ABL and MDR1 transcripts in patients with chronic myeloid leukemia during Imatinib treatment.

Different mechanisms could sustain Imatinib resistance, including overexpression of MDR1, a gene already known to be responsible for multidrug resistance in other hematologic malignancies. In search for a possible correlation, BCR-ABL and MDR1 expression were measured in 115 serial bone marrow samples from 33 CML patients during Imatinib treatment. All patients achieved complete hematologic responses, and 22 patients also achieved complete cytogenetic responses, with median BCR-ABL mRNA values significantly lower than those observed in the group of cases that were persistently Philadelphia positive. All three cases treated during the accelerated phase showed disease progression after an initial period of remission; all presented either increased levels of BCR-ABL or MDR1 3 months before clinical progression. In the subgroup of cases treated during the chronic phase, BCR-ABL and MDR1 levels were significantly correlated after 3 and 6 months (88 and 80%, respectively) but not after 12 months of treatment (32%). Reported data maintain that MDR1 expression would play an important role in Imatinib resistance when the disease is not fully controlled (e.g., progressive disease or during the first months of treatment).

Adult↗

Chronic myeloid leukaemia and hairy cell leukaemia coexisting in a single patient: difficulties at diagnosis and rational of the therapeutic strategy.

Chronic myeloid leukemia (CML) and hairy cell leukemia (HCL) are two distinct haematological disorders. Only one single case of coexistence of the two pathologies at diagnoses has been previously reported. We present a second case of coexistence at diagnosis, indicating the diagnostic procedures involving morphological, immunophenotyping, and molecular testing. We decided to use Interferon as common first-line therapy and Imatinib and Rituximab (anti-CD20 monoclonal antibody), to improve the first-line therapy result, obtaining a complete molecular remission for CML and clinical remission with molecular minimal residual disease for HCL. After a critical analysis of the results, we speculate on the different clonal origin of the two pathologies.

Antibodies, Monoclonal↗

Chimerism does not influence graft-versus-myeloma and graft-versus-host disease in reduced intensity setting.

In this study we serially evaluated the chimerism status in 20 multiple myeloma patients allotransplanted with a reduced intensity regimen. All patients engrafted, with total 75% overall responses and 35% of CRs. After a median follow-up of 35 months, seven patients (35%) died, three of them due to disease progression. Four patients died before day +100, with a TRM of 20%. Nine patients (45%) developed aGVHD and six (40%) had cGVHD. Twenty-five percent of patients achieved full donor chimerism (FDC) before day +100, 42% before day +200 and 75% 24 months after graft. In our series, level of chimerism did not correlate with either the quality of response or aGVHD. No significant differences were found between bone marrow and peripheral blood samples. Analogously, even if donor DNA percentage often resulted higher in the PMN fraction than in the mononuclear one, these differences were not significant after statistical analysis. On the other hand, cGVHD was associated with increased rates of FDC, with 6/6 cases showing a full donor pattern in concomitance of the cGVHD versus 5/9 cases presenting a FDC in the group of patients without cGVHD (p=0.057). The Kaplan-Meier estimates of OS and PFS at 2 years were 59% and 58%, respectively; chimerism pattern did not impact in the predicting clinical outcome. In summary, our study shows that a stable engraftment and high frequency of donor chimerism are achievable after a reduced intensity conditioning regimen. Moreover, even as result of a single center experience, we suggest that chimerism, graft-versus-myeloma and GVHD would represent distinct entities that require larger immunological studies for further clarification.

Adult↗