Publications by authors named "Benedetta Bianchi"

11 Publications

  • Page 1 of 1

MYD88 Detection in IgM Monoclonal Gammopathies: Methodological Considerations for Routine Implementation.

Diagnostics (Basel) 2021 Apr 26;11(5). Epub 2021 Apr 26.

Department of Molecular Biotechnology and Health Sciences, Hematology Division, University of Torino, 10100 Torino, Italy.

In IgM monoclonal gammopathies MYD88 is a prognostic and predictive biomarker of therapy response. MYD88 detection is mainly performed by allele-specific quantitative PCR (ASqPCR), however recently, droplet digital PCR (ddPCR) has been proved to be suitable for MYD88 screening and minimal residual disease monitoring (MRD). This study compared ASqPCR and ddPCR to define the most sensitive method for MYD88 detection in bone marrow (BM), peripheral blood (PB) sorted or unsorted CD19+ cells, and in plasma cell-free DNA (cfDNA). Overall, the analysis showed a good concordance rate (74%) between the two methods, especially in BM samples, while discordances (26%) were mostly in favor of ddPCR (ddPCR+ vs. ASqPCR-) and were particularly evident in samples with low mutational burden, such as PB and cfDNA. This study highlights ddPCR as a feasible approach for MYD88 detection across different specimen types (including cfDNA). Interestingly, its high sensitivity makes CD19+ selection dispensable. On the other hand, our results showed that MYD88 detection on PB samples, especially with ASqPCR, is suboptimal for screening and MRD analysis. Finally, significantly different MYD88 mutational levels observed between Waldenström Macroglobulinemia and IgM monoclonal gammopathy of undetermined significance patients suggest the need for further studies in order to identify possible correlations between mutational levels and risk of progression to Waldenström.
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http://dx.doi.org/10.3390/diagnostics11050779DOI Listing
April 2021

Direct-acting antivirals in relapsed or refractory hepatitis C virus-associated diffuse large B-cell lymphoma.

Leuk Lymphoma 2020 09 28;61(9):2122-2128. Epub 2020 Apr 28.

Department of Molecular Medicine, University of Pavia, Pavia, Italy.

Recent studies have demonstrated feasibility and substantial benefit of direct-acting antivirals (DAAs) administration during or after first-line immune-chemotherapy (I-CT) in patients with hepatitis C virus (HCV)-positive diffuse large B-cell lymphomas (DLBCL). However, data on DAAs used during or after salvage treatments are still lacking. In this study we assessed clinical and virological outcome in 11 patients with relapsed ( = 7) or refractory ( = 4) HCV-positive DLBCL. DAAs were given either concurrently ( = 3) or subsequent ( = 8) to salvage I-CT. Most patients (10 of 11) received sofosbuvir-based regimens. All patients completed their planned courses of DAAs and achieved sustained virological response. DAAs were well tolerated, with no grade ≥2 adverse events. At a median follow-up of 3.6 years four patients died (4-year OS: 76%). In conclusion, we provide evidence that DAAs in HCV-positive relapsed/refractory DLBCL are extremely safe and effective, suggesting that they should be used if HCV eradication was not instituted before.
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http://dx.doi.org/10.1080/10428194.2020.1755859DOI Listing
September 2020

Validation and further potentialities of the novel AWM score for progression risk stratification in patients with asymptomatic Waldenström macroglobulinemia.

Leuk Lymphoma 2020 04 14;61(4):987-989. Epub 2019 Nov 14.

Department of Hematology, University Hospital "Ospedale di Circolo e Fondazione Macchi - ASST Sette Laghi", University of Insubria, Varese, Italy.

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http://dx.doi.org/10.1080/10428194.2019.1689393DOI Listing
April 2020

Early progression as a predictor of survival in marginal zone lymphomas: an analysis from the FIL-NF10 study.

Blood 2019 09 10;134(10):798-801. Epub 2019 Jul 10.

Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

Marginal zone lymphomas (MZLs) are indolent nonfollicular B-cell lymphomas (INFLs) and have heterogeneous clinical behavior. Recently, time to progression of disease at 24 months (POD24) was identified to stratify overall survival (OS) in follicular non-Hodgkin lymphoma and in INFL. Here, we examined the ability of POD24 to predict subsequent OS in a large, international cohort of MZL as part of the NF10 prospective international registry headed by Fondazione Italiana Linfomi (FIL). POD24 was only calculated for MZL patients requiring immediate therapy and was defined as experiencing lymphoma progression within 24 months from diagnosis. Among the 1325 patients enrolled in the NF10 study, we identified 321 patients with MZL for whom immediate therapy was planned right after lymphoma diagnosis. Overall, POD24 was confirmed in 59 patients (18%). Three-year OS for patients with POD24 was 53% with a hazard ratio of 19.5 (95% confidence interval, 8.4-45) compared with patients without POD24 (3-year OS, 95%). Association of POD24 with OS was confirmed for the subgroup of splenic and extranodal MZLs. Assessment of POD24 stratifies subsequent outcome in MZL and identifies a high-risk population. This trial was registered at www.clinicaltrials.gov as #NCT02904577.
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http://dx.doi.org/10.1182/blood.2019001088DOI Listing
September 2019

MYO7A and USH2A gene sequence variants in Italian patients with Usher syndrome.

Mol Vis 2014 23;20:1717-31. Epub 2014 Dec 23.

Department of Genetic Diagnosis, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.

Purpose: To analyze the spectrum of sequence variants in the MYO7A and USH2A genes in a group of Italian patients affected by Usher syndrome (USH).

Methods: Thirty-six Italian patients with a diagnosis of USH were recruited. They received a standard ophthalmologic examination, visual field testing, optical coherence tomography (OCT) scan, and electrophysiological tests. Fluorescein angiography and fundus autofluorescence imaging were performed in selected cases. All the patients underwent an audiologic examination for the 0.25-8,000 Hz frequencies. Vestibular function was evaluated with specific tests. DNA samples were analyzed for sequence variants of the MYO7A gene (for USH1) and the USH2A gene (for USH2) with direct sequencing techniques. A few patients were analyzed for both genes.

Results: In the MYO7A gene, ten missense variants were found; three patients were compound heterozygous, and two were homozygous. Thirty-four USH2A gene variants were detected, including eight missense variants, nine nonsense variants, six splicing variants, and 11 duplications/deletions; 19 patients were compound heterozygous, and three were homozygous. Four MYO7A and 17 USH2A variants have already been described in the literature. Among the novel mutations there are four USH2A large deletions, detected with multiplex ligation dependent probe amplification (MLPA) technology. Two potentially pathogenic variants were found in 27 patients (75%). Affected patients showed variable clinical pictures without a clear genotype-phenotype correlation.

Conclusions: Ten variants in the MYO7A gene and 34 variants in the USH2A gene were detected in Italian patients with USH at a high detection rate. A selective analysis of these genes may be valuable for molecular analysis, combining diagnostic efficiency with little time wastage and less resource consumption.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4279600PMC
December 2015

Identification of autoantibodies against inner ear antigens in a cohort of children with idiopathic sensorineural hearing loss.

Autoimmunity 2013 Dec 15;46(8):525-30. Epub 2013 Aug 15.

Rheumatology Unit, Anna Meyer Children's Hospital and University of Florence , Florence , Italy .

Immune-mediated pathogenesis has been suggested for idiopathic sensorineural hearing loss. Recent studies have investigated the relationship between idiopathic sensorineural hearing loss and autoantibodies against inner ear antigens. We conducted a prospective, observational study in a series of pediatric patients affected by idiopathic sensorineural hearing loss. Autoantibodies against inner ear (anti-Cogan peptide, anti-connexin 26, anti-DEP1/CD148 and anti-reovirus), previously described in the serum of patients with Cogan's syndrome, were detected in our population. The characteristics of children whose results were positive were also evaluated to verify if clinical data, disease progression and response to treatment could confirm an immune-mediated pathogenesis. Eleven patients were enrolled and 9 of them were positive for inner ear antibodies. Non-organ specific autoantibodies were present in 5 children out of 9. An immune-mediated condition was diagnosed in 2 cases and minor immune manifestations were found in 2 additional patients. In 5 cases hearing loss remained stable without therapy, while 4 children developed progression. Two subjects were treated with corticosteroids and methotrexate, achieving hearing improvement. Another subject showed stabilization on methotrexate. Inner ear autoantibodies can be positive in children with autoimmune sensorineural hearing loss, and in conjunction with clinical data may assist the clinician in identifying a subset amenable for immune modulation therapy. Large prospective studies are needed to investigate usefulness, diagnostic and prognostic role of these autoantibodies.
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http://dx.doi.org/10.3109/08916934.2013.822074DOI Listing
December 2013

Inner ear abnormalities in four patients with dRTA and SNHL: clinical and genetic heterogeneity.

Pediatr Nephrol 2009 Nov 29;24(11):2147-53. Epub 2009 Jul 29.

Department of Clinical Pathophysiology, University of Florence, Italy.

A significant number of patients affected by autosomal recessive primary distal renal tubular acidosis (dRTA) manifest sensorineural hearing loss (SNHL). Mutations in ATP6V1B1 are associated with early onset SNHL, whereas ATP6V0A4 mutations have been described in dRTA and late-onset SNHL. Enlarged vestibular aqueduct (EVA) was described in patients with recessive dRTA and SNHL, and recently, this abnormality has been associated with mutations in the ATP6V1B1 gene. In our study, we evaluated the presence of inner-ear abnormalities in four patients affected by dRTA and SNHL, characterized by molecular analysis. Two patients affected by severe dRTA with early onset SNHL showed the same mutation in the ATP6V1B1 gene and bilateral EVA with a different degree of severity. The other two presented similar clinical manifestations of dRTA and different mutations in the ATP6V0A4 gene: one patient, showing EVA, developed an early SNHL, whereas in the other one, the SNHL appeared in the second decade of life and the vestibular aqueduct was normal. Our study confirms the association of EVA and mutations in the ATP6V1B1 gene and demonstrates that mutations in the ATP6V0A4 gene can also be associated with EVA probably only when the SNHL has an early onset. The pathophysiology of SNHL and EVA are still to be defined.
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http://dx.doi.org/10.1007/s00467-009-1261-3DOI Listing
November 2009

Prognostic significance of cyclooxygenase-2 pathway and angiogenesis in head and neck squamous cell carcinoma.

Hum Pathol 2002 Jul;33(7):708-14

Department of Oto-Neuro-Ophthalmologic Surgery, University of Florence Medical School, Florence, Italy.

Prostaglandins play a critical role in tumor development and growth by regulating numerous biologic processes, including tumor angiogenesis, with clear prognostic and therapeutic implications. The aim of this study was to investigate the prognostic relevance of cyclooxygenase-2 (COX-2) pathway activation in head and neck squamous cell carcinoma (HNSCC). COX-2 activity was analyzed in 52 consecutive patients by assessing protein expression and prostaglandin E(2) (PgE(2)) levels and was then correlated to vascular endothelial growth factor (VEGF) expression and tumor angiogenesis. We evaluated the prognostic impact of these parameters by Kaplan-Meier and Cox survival analysis. COX-2 expression by tumor cells was closely correlated to VEGF expression and to tumor vascularization. According to Kaplan-Meier analysis, patients with COX-2 tumor overexpression and with higher PgE(2) tumor levels had significantly shorter overall survival estimates (P = 0.022 and P = 0.033, respectively). Analogously, patients with more-vascularized tumors had worse survival than those with less-vascularized cancers (P = 0.032). Cox multivariate analysis demonstrated that the most significant prognostic factors were presence of lymph node metastasis, tumor vascularization, COX-2 protein expression, and PgE(2) tumor levels. This study demonstrates a close correlation between COX-2 pathway, VEGF expression, and tumor angiogenesis in HNSCC. In addition, COX-2 overexpression and higher tumor vascularization appear to predict a shorter survival in patients with head and neck cancer.
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http://dx.doi.org/10.1053/hupa.2002.125376DOI Listing
July 2002