17 results on '"Idalucia Ferrara"'
Search Results
2. P1544: IMPACT OF SARS-COV 2 INFECTION, IN TREATED NHL-B AND HD, AFTER VACCINATION AND PREVENTIVE THERAPY WITH ANTIBODIES: OUR EXPERIENCE
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Luca Pezzullo, Valentina Giudice, Matteo D’addona, Danilo DE Novellis, Idalucia Ferrara, Raffaele Fontana, Roberto Guariglia, Serena Luponio, Maria Carmela Martorelli, Laura Mettivier, Bianca Serio, and Carmine Selleri
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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3. Clinical efficacy of azacytidine and venetoclax and prognostic impact of Tim-3 and galectin-9 in acute myeloid leukemia and high-risk myelodysplastic syndromes: A single-center real-life experience
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Valentina Giudice, Bianca Serio, Idalucia Ferrara, Paola Manzo, Marisa Gorrese, Rita Pepe, Angela Bertolini, Francesca D’Alto, Francesco Verdesca, Maddalena Langella, Amelia Filippelli, and Carmine Selleri
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hypomethylating agents ,bcl-2 inhibitor ,acute myeloid leukemia ,myelodysplastic syndromes ,prognosis ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Treatment of acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS) is difficult in older patients with comorbidities and high-risk disease factors. Venetoclax, the first-in-class Bcl-2 inhibitor, has proven efficacy and safety in combination with azacytidine for treatment of high-risk myeloid diseases. In this single-center real-life retrospective study, a total of 27 consecutive patients treated with azacytidine plus venetoclax were included, and clinical outcomes, hematological improvements, and biomarkers of responsiveness to therapy were compared to those observed in an historical cohort of 95 consecutive patients treated with azacytidine as single agent. Azacytidine plus venetoclax was effective and safe in older and frail AML and high-risk MDS patients, with median overall survival of 22.3 months, higher than that reported in phase III trial (14.7 months), and higher than that of historical cohort (5.94 months). Progression-free survival was higher in patients treated with the drug combination compared to those treated with azacytidine as single agent (p = 0.0065). Clinical benefits might increase when azacytidine and venetoclax are administered as upfront therapy (p = 0.0500). We showed that Tim-3 expression could be a promising therapeutic target in refractory/relapsed patients, and galectin-9 a biomarker of responsiveness to therapy. Moreover, patients treated with azacytidine and venetoclax displayed a higher overall survival regardless the presence of negative prognostic markers at diagnosis (e.g., increased WT1 copies and/or normalized blast count). These encouraging results in a real-world setting supported efficacy and safety of azacytidine plus venetoclax as upfront therapy in AML and high-risk MDS, with clinical outcomes comparable to those of clinical trials when an appropriate venetoclax management with bone marrow assessment at every first, second, fourth, and eighth cycle, and dose adjustments for toxicities are performed.
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- 2022
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4. Serum Free Light-Chain Ratio at Diagnosis Is Associated with Early Renal Damage in Multiple Myeloma: A Case Series Real-World Study
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Danilo De Novellis, Raffaele Fontana, Angela Carobene, Bianca Serio, Idalucia Ferrara, Maria Carmen Martorelli, Laura Mettivier, Roberto Guariglia, Serena Luponio, Immacolata Ruggiero, Matteo D’Addona, Tiziana Di Leo, Valentina Giudice, and Carmine Selleri
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multiple myeloma ,free light-chain ratio ,renal failure ,prognosis ,free light chains ,Biology (General) ,QH301-705.5 - Abstract
The serum free light-chain (FLC) ratio is a sensitive tool for the differential diagnosis of plasma cell disorders and is biomarker of multiple myeloma (MM) progression from premalignant conditions. Here, we investigate the potential role of FLC ratio at diagnosis in identifying early renal damage in MM patients and other correlations with clinical, laboratory, and molecular findings. A total of 34 MM patients who had undergone autologous stem cell transplantation were included in this retrospective case series study, and FLC quantification was performed with nephelometric assays. In our study, sFLC ratio was significantly associated with light-chain MM and β-2 microglobulin levels, likely indicating a high disease burden at diagnosis, especially in patients without heavy chain M-protein at serum electrophoresis. Moreover, the sFLC ratio was inversely correlated with glomerular filtration rate, possibly identifying early renal damage in MM patients. Our preliminary results confirm the importance of early sFLC evaluation, especially in patients with the light-chain MM type and low disease burden, to minimize the risk of late renal failure.
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- 2022
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5. WT1 Expression Levels Combined with Flow Cytometry Blast Counts for Risk Stratification of Acute Myeloid Leukemia and Myelodysplastic Syndromes
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Valentina Giudice, Marisa Gorrese, Rosa Vitolo, Angela Bertolini, Rossella Marcucci, Bianca Serio, Roberto Guariglia, Idalucia Ferrara, Rita Pepe, Francesca D’Alto, Barbara Izzo, Antonio Pedicini, Nunzia Montuori, Maddalena Langella, and Carmine Selleri
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Wilms’ tumor 1 ,acute myeloid leukemia ,myelodysplastic syndrome ,prognosis ,flow cytometry ,Biology (General) ,QH301-705.5 - Abstract
Wilm’s tumor 1 (WT1), a zinc-finger transcription factor and an epigenetic modifier, is frequently overexpressed in several hematologic disorders and solid tumors, and it has been proposed as diagnostic and prognostic marker of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). However, the exact role of WT1 in leukemogenesis and disease progression remains unclear. In this real-world evidence retrospective study, we investigated prognostic role of WT1-mRNA expression levels in AML and MDS patients and correlations with complete blood counts, flow cytometry counts, and molecular features. A total of 71 patients (AML, n = 46; and MDS, n = 25) were included in this study, and WT1 levels were assessed at diagnosis, during treatment and follow-up. We showed that WT1 expression levels were inversely correlated with normal hemopoiesis in both AML and MDS, and positively associated with blast counts. Flow cytometry was more sensitive and specific in distinguishing normal myeloid cells from neoplastic counterpart even just using linear parameters and CD45 expression. Moreover, we showed that a simple integrated approach combining blast counts by flow cytometry, FLT3 mutational status, and WT1 expression levels might be a useful tool for a better prognostic definition in both AML and MDS patients.
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- 2021
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6. Endocrinopathies after Allogeneic and Autologous Transplantation of Hematopoietic Stem Cells
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Francesco Orio, Giovanna Muscogiuri, Stefano Palomba, Bianca Serio, Mariarosaria Sessa, Valentina Giudice, Idalucia Ferrara, Libuse Tauchmanovà, Annamaria Colao, and Carmine Selleri
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Technology ,Medicine ,Science - Abstract
Early and late endocrine disorders are among the most common complications in survivors after hematopoietic allogeneic- (allo-) and autologous- (auto-) stem cell transplant (HSCT). This review summarizes main endocrine disorders reported in literature and observed in our center as consequence of auto- and allo-HSCT and outlines current options for their management. Gonadal impairment has been found early in approximately two-thirds of auto- and allo-HSCT patients: 90–99% of women and 60–90% of men. Dysfunctions of the hypothalamus-pituitary-growth hormone/insulin growth factor-I axis, hypothalamus-pituitary-thyroid axis, and hypothalamus-pituitary-adrenal axis were documented as later complicances, occurring in about 10, 30, and 40–50% of transplanted patients, respectively. Moreover, overt or subclinical thyroid complications (including persistent low-T3 syndrome, chronic thyroiditis, subclinical hypo- or hyperthyroidism, and thyroid carcinoma), gonadal failure, and adrenal insufficiency may persist many years after HSCT. Our analysis further provides evidence that main recognized risk factors for endocrine complications after HSCT are the underlying disease, previous pretransplant therapies, the age at HSCT, gender, total body irradiation, posttransplant derangement of immune system, and in the allogeneic setting, the presence of graft-versus-host disease requiring prolonged steroid treatment. Early identification of endocrine complications can greatly improve the quality of life of long-term survivors after HSCT.
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- 2014
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7. Real-world evidence of cytomegalovirus reactivation in non-Hodgkin lymphomas treated with bendamustine-containing regimens
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Valentina Giudice, Pasquale Pagliano, Idalucia Ferrara, Bianca Serio, Roberto Guariglia, Alessandro Bruno, Maria Carmen Martorelli, Rosario Bianco, R Fontana, Emilia Vaccaro, Carmine Selleri, Nunzia Montuori, L Pezzullo, Amelia Filippelli, Laura Mettivier, Pezzullo, L., Giudice, V., Serio, B., Fontana, R., Guariglia, R., Martorelli, M. C., Ferrara, I., Mettivier, L., Bruno, A., Bianco, R., Vaccaro, E., Pagliano, P., Montuori, N., Filippelli, A., and Selleri, C.
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Bendamustine ,Oncology ,medicine.medical_specialty ,cytomegaloviru ,medicine.medical_treatment ,Secondary infection ,Congenital cytomegalovirus infection ,Hematopoietic stem cell transplantation ,chemotherapy ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,cytomegalovirus ,Dexamethasone ,Chemotherapy ,business.industry ,non-Hodgkin lymphoma ,General Medicine ,medicine.disease ,immunity ,Lymphoma ,030220 oncology & carcinogenesis ,Medicine ,Rituximab ,business ,Research Article ,030215 immunology ,medicine.drug - Abstract
Cytomegalovirus (CMV) reactivation during chemotherapy or after organ or hematopoietic stem cell transplantation is a major cause of morbidity and mortality, and the risk of reactivation increases with patients’ age. Bendamustine, an alkylating agent currently used for treatment of indolent and aggressive non-Hodgkin lymphomas, can augment the risk of secondary infections including CMV reactivation. In this real-world study, we described an increased incidence of CMV reactivation in older adults (age >60 years old) with newly diagnosed and relapsed/refractory indolent and aggressive diseases treated with bendamustine-containing regimens. In particular, patients who received bendamustine plus rituximab and dexamethasone were at higher risk of CMV reactivation, especially when administered as first-line therapy and after the third course of bendamustine. In addition, patients with CMV reactivation showed a significant depression of circulating CD4+ T cell count and anti-CMV IgG levels during active infection, suggesting an impairment of immune system functions which are not able to properly face viral reactivation. Therefore, a close and early monitoring of clinical and laboratory findings might improve clinical management and outcome of non-Hodgkin lymphoma patients by preventing the development of CMV disease in a subgroup of subjects treated with bendamustine more susceptible to viral reactivation.
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- 2021
8. Low-Density Granulocytes Are Decreased in Acute Myeloid Leukemia and in Myelodysplastic Syndromes with Negative Prognostic Factors
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Valentina Giudice, Rossella Marcucci, Maddalena Langella, Rita Pepe, Carmine Selleri, Maria Teresa Buonanno, Rosa Vitolo, Matteo D'Addona, Maria Carmen Martorelli, Bianca Serio, Marisa Gorrese, Idalucia Ferrara, Angela Bertolini, and Paola Manzo
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business.industry ,Myelodysplastic syndromes ,Immunology ,medicine ,Cancer research ,Low density ,Myeloid leukemia ,Cell Biology ,Hematology ,medicine.disease ,business ,Biochemistry - Abstract
Introduction. Myelodysplastic syndromes (MDS), a group of clonal hematological diseases, are characterized by ineffective hematopoiesis, progressive peripheral blood (PB) cytopenia(s), and increased risk of developing acute myeloid leukemia (AML). Classification and risk stratification are constantly under revision for a better estimation of prognosis in those patients. Investigation of immune biomarkers is needed, because immune dysregulation also plays an important role in dysplastic hemopoiesis and immunological escape of neoplastic clones. Here, we studied frequency of low-density granulocytes (LDGs), a neutrophil subset with immunoregulatory functions, in MDS and AML at diagnosis and during treatments. Methods. A total of 17 patients (M/F, 14/12; median age, 69 years old; range, 21-84 years) and seven healthy subjects were enrolled at the Hematology and Transplant Center, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", Salerno, Italy, between October 2020 and July 2021. Patients were diagnosed with AML (N = 7), or MDS (N = 10) according to the 2016 World Health Organization criteria. For immunophenotyping, fresh EDTA whole PB was stained with the ollowing antibodies: CD45; HLA-DR; CD15; CD3; CD56; CD19; CD11b; CD33; CD34; CD14; and CD16 (all from Beckman Coulter, Brea, CA). Acquisition was carried out using a Navios EX flow cytometer, and Navios software v1.3 (Beckman Coulter). Post-acquisition compensation and analysis were performed using FlowJo software (v.10.7.1, Becton Dickinson). LDGs were identified as CD3-CD56-CD19-CD11b+CD33+CD14-CD15+ cells, following previously published gating strategies (Rahman S, et al. Ann Rheum Dis. 2019). Data were analyzed using Prism (GraphPad software, La Jolla, CA). A P < 0.05 was considered statistically significant. Results. Frequencies of circulating LDGs were significantly reduced in AML patients at diagnosis compared to controls (P = 0.0018) and MDS (P = 0.0077) and were slightly decreased compared to AML in complete remission (P = 0.1605). MDS patients were then divided based on Revised International Prognostic Scoring System (IPSS-R), and very-low and low-risk MDS patients displayed significantly higher circulating LDG frequencies compared to AML at diagnosis (P = 0.0083), while no differences were described between AML at baseline and intermediate-risk MDS (P = 0.1103). Subsequently, LDGs were correlated with clinical and phenotypic features by correlation analysis showing significant negative correlations between LDGs and blasts identified by flow cytometry (r = -0.5463; P = 0.0057) but not by cytology (P = 0.1346), between LDGs and lymphocytes (r = -0.4407; P = 0.0311) or flow cytometric normalized blast count (NBC; r = -0.5283; P = 0.0096) as previously defined (Giudice V, et al. Biomedicines. 2021). A slight negative correlation was described between LDGs and WT1 expression levels (r = -0.5369; P = 0.0719), particularly evident in MDS patients (r = -0.9980; P = 0.0402), supporting our previous findings of negative prognostic impact of WT1 expression in MDS and AML. Finally, we investigated CD16 expression on LDGs, because CD16 is essential for neutrophil degranulation. Despite no differences were described between percentage of LDG subsets among patients' groups, various correlations were identified by Pearson analysis. In particular, CD16+ LDGs negatively correlated with blasts (P = 0.0229), while positively correlated with lymphocytes (P = 0.0404) detected by flow cytometry. Conversely, CD16int and CD16- LDGs negatively correlated with lymphocytes (P = 0.0109 and P = 0.0021, respectively) and positively correlated with granulocytes identified by flow cytometry (P = 0.0024 and P = 0.0008, respectively). In addition, CD16int LDGs negatively correlated with blasts detected by flow cytometry (r = -0.65; P = 0.0414). Conclusions. Our preliminary results suggested a possible role of LDGs in prognostic definition of AML and MDS patients especially when combined with other biomarkers, such as WT1 expression levels or NBC. Moreover, our data supported the hypothesis of biological heterogeneity of granulocytes, as LDG subsets variously correlated with lymphocytes and leukemic cells suggesting different roles in suppression or activation of immune responses. However, our findings need further validation in larger cohorts and in in vitro studies. Disclosures No relevant conflicts of interest to declare.
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- 2021
9. Wt1 expression levels combined with flow cytometry blast counts for risk stratification of acute myeloid leukemia and myelodysplastic syndromes
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Roberto Guariglia, Nunzia Montuori, Rossella Marcucci, Maddalena Langella, Rosa Vitolo, Antonio Pedicini, Rita Pepe, Bianca Serio, Valentina Giudice, Idalucia Ferrara, Barbara Izzo, Marisa Gorrese, Carmine Selleri, Angela Bertolini, Francesca D'Alto, Giudice, V., Gorrese, M., Vitolo, R., Bertolini, A., Marcucci, R., Serio, B., Guariglia, R., Ferrara, I., Pepe, R., D'Alto, F., Izzo, B., Pedicini, A., Montuori, N., Langella, M., and Selleri, C.
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Oncology ,medicine.medical_specialty ,Wilms’ tumor 1 ,Prognosi ,Medicine (miscellaneous) ,Article ,General Biochemistry, Genetics and Molecular Biology ,Flow cytometry ,03 medical and health sciences ,0302 clinical medicine ,Hematologic disorders ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Mutational status ,lcsh:QH301-705.5 ,Acute myeloid leukemia ,medicine.diagnostic_test ,business.industry ,Myelodysplastic syndromes ,Myeloid leukemia ,Retrospective cohort study ,medicine.disease ,Haematopoiesis ,lcsh:Biology (General) ,030220 oncology & carcinogenesis ,Risk stratification ,prognosis ,business ,Myelodysplastic syndrome ,030215 immunology - Abstract
Wilm’s tumor 1 (WT1), a zinc-finger transcription factor and an epigenetic modifier, is frequently overexpressed in several hematologic disorders and solid tumors, and it has been proposed as diagnostic and prognostic marker of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). However, the exact role of WT1 in leukemogenesis and disease progression remains unclear. In this real-world evidence retrospective study, we investigated prognostic role of WT1-mRNA expression levels in AML and MDS patients and correlations with complete blood counts, flow cytometry counts, and molecular features. A total of 71 patients (AML, n = 46, and MDS, n = 25) were included in this study, and WT1 levels were assessed at diagnosis, during treatment and follow-up. We showed that WT1 expression levels were inversely correlated with normal hemopoiesis in both AML and MDS, and positively associated with blast counts. Flow cytometry was more sensitive and specific in distinguishing normal myeloid cells from neoplastic counterpart even just using linear parameters and CD45 expression. Moreover, we showed that a simple integrated approach combining blast counts by flow cytometry, FLT3 mutational status, and WT1 expression levels might be a useful tool for a better prognostic definition in both AML and MDS patients.
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- 2021
10. Hemopoiesis and Immune Cell Perturbations during Venetoclax Plus Azacytidine Treatment in Acute Myeloid Leukemia
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Serena Luponio, Angela Bertolini, Francesca D'Alto, Bianca Cuffa, Bianca Serio, Roberto Guariglia, Carmine Selleri, Laura Mettivier, Idalucia Ferrara, L Pezzullo, Marisa Gorrese, Valentina Giudice, Matteo D'Addona, and Danilo De Novellis
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Venetoclax ,business.industry ,Immunology ,Cell ,Myeloid leukemia ,Cell Biology ,Hematology ,Biochemistry ,chemistry.chemical_compound ,Haematopoiesis ,medicine.anatomical_structure ,Immune system ,chemistry ,medicine ,Cancer research ,business - Abstract
Treatment of acute myeloid leukemia (AML) in elderly is still challenging. Indeed, high-dose chemotherapy followed by hematopoietic stem cell transplantation with myeloablative regimens is not always feasible because patients are often unfit and have several comorbidities; however, they frequently show multiple negative prognostic factors and have a worse overall survival compared to younger adults. Venetoclax, the first-in-class Bcl-2 antagonist and first approved for treatment of chronic lymphocytic leukemia, inhibits the anti-apoptotic functions of Bcl-2 inducing apoptosis and tumor growth arrest. Venetoclax is also used in combination with azacytidine, or decitabine, or low-dose cytarabine for treatment of elderly newly diagnosed AML. However, several mechanisms of resistance have already been described, such as increased expression of other anti-apoptotic proteins by the leukemic clone. In this case series, we investigated hematopoiesis and immune cell perturbations during venetoclax plus azacytidine treatment in elderly AML patients. A total of six AML patients (M/F, 2/4; median age, 71 years old; range, 63-79 years) were retrospectively evaluated at the Hematology and Transplant Center, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", Salerno, Italy. Patients received a diagnosis of AML based on the 2016 World Health Organization (WHO) criteria and chemotherapy with azacytidine 75 mg/m 2 daily for 7 days per cycle and venetoclax 70 mg/daily. Two patients were NPM1 mutated (one of them also had mutated IDH1, VAF 27.2%), while all subjects had FLT3 wild type. Based on the 2017 European LeukemiaNet risk classification, two patients had favorable risk and four intermediate. Median follow-up was 10.1 months (range, 4.9-16.6 months), and all patients were in partial or complete remission at the time of writing. Flow cytometry immunophenotype, complete blood counts (CBCs), and WT1 expression levels were performed at diagnosis and after every cycle of therapy as per our institutional guidelines. In our case series, leukemic cells were already decreased after the first cycle of therapy (blasts by flow cytometry + SD, 54.7+39.9% vs 4.2+5.4%, diagnosis vs post I cycle; P = 0.0671; paired t-test performed), while normal granulocytes detected by flow cytometry recovered only after the third cycle of therapy (20.7+23.7% vs 53+6.6%, diagnosis vs post III cycle; P = 0.1396; uncorrected Fisher's mixed model performed). Treated patients also displayed a contextual decreased in WT1 expression levels (normalized WT1 copy number + SD, 1810+2723 copies vs 201+132.9 copies, diagnosis vs post I cycle; P = 0.2660; paired t-test performed). Platelet count tended to increase after the first cycle (P = 0.0680); however, at the end of the second cycle, half of patients were again thrombocytopenic (platelets < 100 x 10 3/µL). Interestingly, percentage of lymphocytes detected by flow cytometry were significantly increased after the second cycle of azacytidine plus venetoclax compared to baseline and after the first cycle of therapy (mean+SD, 13.5+13.3% vs 48+8.7%, diagnosis vs post II cycle; P = 0.0167; and vs 28+11.3%, vs post III cycle; P = 0.0480), likely because an increase in Natural Killer (NK) cell frequency peaking after the second cycle (mean+SD, 19.4+4.4% vs 32.5+15.1%, diagnosis vs post II cycle; P = 0.1383). Moreover, five out of six patients displayed expansion of plasma cells detected by flow cytometry in the bone marrow after the first cycle: in particular, one case patient had expansion of aberrant CD45-/dimCD38++CD138++CD56+CD19- plasma cells, while one subject showed only a transient appearance of clonal plasma cells after the second cycle. No differences in bone marrow monocyte frequencies were described during treatment. Our preliminary results added evidence to efficacy and safety of the combination of venetoclax and azacytidine in treatment of elderly AML in a real-world setting. These drugs might synergistically function on hematopoiesis by inducing apoptosis of neoplastic cells while favoring differentiation of other lineages, as suggested by the expansion of plasma cells, or triggering NK-mediated immunosurveillance. However, prognostic and clinical significance of plasma cell and NK cell expansion in the setting of AML treatment needs to be further explored in larger prospective cohorts. Disclosures No relevant conflicts of interest to declare.
- Published
- 2021
11. Immune dysregulation and dyserythropoiesis in the myelodysplastic syndromes
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Carmela Palladino, Fiorella Alfinito, Giuseppe Terrazzano, Umberto Giani, Idalucia Ferrara, Roberta Della Pepa, Luigiana Luciano, Michela Sica, and Giuseppina Ruggiero
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medicine.medical_specialty ,Hematology ,Lymphocyte ,Myelodysplastic syndromes ,Immune dysregulation ,Biology ,medicine.disease_cause ,medicine.disease ,medicine.anatomical_structure ,Immune system ,hemic and lymphatic diseases ,Immunopathology ,Internal medicine ,Immunology ,medicine ,Bone marrow ,CD8 - Abstract
The myelodysplastic syndromes (MDS) are clonal disorders characterised by ineffective haematopoiesis with high risk of leukaemia progression. The relevance of immune-dysregulation for emergence, dominance and progression of dysplastic clones has been suggested, but valuable criteria to obtain insight into these connections are lacking. This study showed significant increase of CD8 lymphocytes and mature B cells in the bone marrow (BM) compared to peripheral blood (PB) of low risk MDS patients. Different BM levels of Regulatory T cells (Treg) identified two sub-groups in these patients; only the sub-group with lower Treg percentage showed BM recruitment of CD8 lymphocytes. Different levels of CD54 on BM CD8 cells revealed two sub-groups of Intermediate-1 (Int-1) patients. The sub-group with higher CD54 expression on BM CD8 showed high levels of this molecule also on CD4 cells. BM recruitment of CD8 lymphocytes in the low risk group and/or the presence of high CD54 expression on BM CD8 in Int-1 patients were associated with more pronounced dyserythropoiesis and erythropoietin treatment. Our data shed light on the involvement of immune-mediated mechanisms in Low and Int-1 risk MDS patients and suggest that BM versus PB levels of immune effectors could represent useful criteria for a more homogeneous grouping of MDS patients.
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- 2010
12. Bone and soft tissue non-Hodgkin lymphoma of the maxillofacial area: report of two cases, literature review and new therapeutic strategies
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Giuseppe Pantaleo, Alessandro Vatrella, Vincenzo Giuseppe Di Crescenzo, Idalucia Ferrara, Massimo Amato, Antonio Cortese, and I. Cozzolino
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medicine.medical_specialty ,Histology ,Soft Tissue Neoplasms ,stomatognathic system ,immune system diseases ,hemic and lymphatic diseases ,Rx imaging ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Chemotherapy ,Humans ,Non-Hodgkin lymphoma Rx imaging Maxillofacial area Literature review Fine needle cytology Histology Chemotherapy Differential diagnosis ,Pathological ,Non-Hodgkin lymphoma ,Aged ,Literature review ,business.industry ,Lymphoma, Non-Hodgkin ,Head and neck tumors ,Soft tissue ,General Medicine ,Middle Aged ,medicine.disease ,Fine needle cytology ,Lymphoma ,stomatognathic diseases ,Mandibular Neoplasms ,Maxillofacial area ,Head and Neck Neoplasms ,Radiological weapon ,B-Cell Non-Hodgkin Lymphoma ,Hodgkin lymphoma ,Differential diagnosis ,Surgery ,Female ,Radiology ,Lymphoma, Large B-Cell, Diffuse ,Facial Neoplasms ,business ,Tomography, X-Ray Computed - Abstract
Primary mandibular non-Hodgkin lymphoma (NHL) and soft tissues NHL of the maxillofacial are extremely rare representing a minimal percentage of the head and neck tumors. Two cases of bone and soft tissue maxillofacial NHL are reported. Clinical, radiological and pathological features are described and the therapeutic procedures are discussed accordingly. Mandibular radiologic features have been carefully analyzed and discussed to achieve an early and accurate diagnosis avoiding improper dental therapies.
- Published
- 2014
13. The Role of B Regulatory Cells in the Immunological Escape of Tumor Cells in Hodgkin Lymphoma
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M Rocco, G Villani, Valentina Giudice, Carmine Selleri, R Rosamilio, L Pezzullo, Bianca Serio, and Idalucia Ferrara
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biology ,business.industry ,T cell ,Dacarbazine ,Immunology ,Cell Biology ,Hematology ,Biochemistry ,CD19 ,Vinblastine ,Interleukin 10 ,medicine.anatomical_structure ,biology.protein ,Medicine ,Cytotoxic T cell ,IL-2 receptor ,business ,CD8 ,medicine.drug - Abstract
Hodgkin and Reed-Sternberg (HRS) cells in classical Hodgkin Lymphoma (HL) are surrounded by a rich inflammatory infiltrate which aids in their survival and escape from cytotoxic CD8+ T cells (CTLs) and Natural Killer cells (NKs). Within HL environment, T regulatory cells (Tregs) directly suppress the activity of CTLs and NKs, enhancing the tolerance against HRS cells. B regulatory cells (Bregs) have been shown to support the differentiation of Tregs through IL-10 production; thus, we hypothesized that they could have a role in the pathophysiology of HL. We evaluated 30 classic HL patients (M/F: 18/12; median age, 31 years, range 15-62) and 5 healthy controls (HC) for circulating peripheral blood (PB) Bregs, Tregs, CTLs, NKs, and NKTs. Twenty-four of them were new-diagnosed patients (NwHL) and 6 received a previous diagnosis of HL but were in complete remission (CR) for more than 12 months (PvHL). NwHL patients were divided according to the International Prognostic Score (IPS) and the Ann-Arbor Staging System. All subjects were treated following the ABVD protocol (doxorubicin 25 mg/m2, bleomycin 10 U/m2, vinblastine 6 mg/m2, and dacarbazine 375 mg/m2). Flow cytometry was performed on heparinized PB samples with a 5-color Beckman Coulter Cytomics FC500 flow cytometer. Breg (CD19+CD24+), Treg (CD3+CD4+CD25+), CTL (CD3+CD8+), NK (CD3-CD56+), and NKT (CD3+CD56+) levels were measured simultaneously with the PET/CT evaluations, ie at diagnosis, at the end of the second ABVD administration, at the end of treatment, and at 6 and/or 12 months off-therapy. Moreover, Breg levels were compared to IPS and Ann-Arbor staging groups, and also were correlated to the erythrocyte sedimentation rate (ESR) and to the absolute lymphocyte count (ALC). We found decreased circulating Bregs in NwHL and PvHL patients compared to controls (0.39% vs 0.875% vs 1.813%, respectively, p Our preliminary data suggest involvement of Bregs in the escape and survival of HRS cells during active disease. Peripheral blood may mirror disease activity in lymphoid tissues. Thus, the decrease of circulating Bregs may be related to the recruitment of these cells to the tumor site; amplification of the Bregs/Tregs ratio may result in a greater Breg-dependent Treg activation with subsequent inhibition of CTL and NK function. Additionally, the normalization of Bregs and the Bregs/Tregs ratio after chemotherapy could be used to predict disease remission. While larger prospective studies are required to validate these results, we present intriguing evidence of the involvement of Bregs in the pathophysiology of HL. Disclosures No relevant conflicts of interest to declare.
- Published
- 2016
14. How to Improve the Definition of Chronic Lymphocytic Leukemia Outcome Using a Simple Flow Cytometric Score Based on CD49d and Homing Marker Expression
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Bianca Serio, G Villani, Luigi Marino, Valentina Giudice, S Annunziata, Carmine Selleri, Idalucia Ferrara, R Rosamilio, L Pezzullo, R Fontana, and M Rocco
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Oncology ,medicine.medical_specialty ,business.industry ,Chronic lymphocytic leukemia ,Immunology ,Cell Biology ,Hematology ,CD49d ,medicine.disease ,Biochemistry ,Chemotherapy regimen ,Immunophenotyping ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Platelet Count measurement ,Hemoglobin measurement ,business ,Homing (hematopoietic) - Abstract
The identification of new molecular markers in Chronic Lymphocytic Leukemia (CLL) allowed to better define prognosis and clinical outcome. The actual staging systems could estimate the prognosis, but not the rapidity of disease evolution. Neither the identification of new molecular markers did allow to foresee the evolution and clinical response, because discordant findings were mostly reported. The aim of the present study was (1) to confirm the independent prognostic role of CD49d as a single marker in CLL patients, (2) to investigate the relationship between CD49d and other well-established CLL-membrane predictor markers (CD5, CD11c, CD20 and CD38) or clinical staging systems and (3) to evaluate the role of an immunophenotypic score based on the flow-cytometric detection of CD5, CD11c, CD20, CD38 and CD49d in the work up of CLL staging. Heparinized whole blood was collected from 68 CLL patients for immunophenotyping using the following antibodies: anti kappa, anti-lambda, CD5, CD11c, CD19, CD20, CD23, CD38, CD45, CD49d. A scoring system was elaborated combining 5 membrane markers: CD5, CD11c, CD20, CD38 and CD49d. Antigens were divided in two groups, favorable (CD5 and CD20) and unfavorable (CD11c, CD38 and CD49d) prognostic markers, and the cut-off of positivity was chosen according to the literature (30% for CD5, CD11c, CD20 and CD38, and 45% for CD49d). A value of "0" or "1" ("2" only for CD49d positivity) was assigned according to antigen expression. Finally, we defined a favorable phenotype when the sum of all the cytometric features was equal or less than 2, conversely the unfavorable phenotype was defined for a sum equal or greater than 3 (between 3 and 6). Flow cytometric analysis showed high CD49d expression in CD19+ cells in 47% of patients (n=32), and high CD38 expression in 44% of subjects (n=30), simultaneously expressed in 28% of patients (n=19). The 19% (n=13) of all CLL patients were CD5-, and interestingly the 85% of them showed higher expression of CD49d. Linear correlation was found between CD49d and CD38 (r2=0.08772, p=0.0142), and between CD49d and CD20 expression (r2=0.2490, p45% of CD49d positive cells. Four patients with Unfavorable Phenotype received chemotherapy with an ORR of 25%. Furthermore, a small population (n=16) of our CLL cohort was also studied for genetic abnormalities using FISH technique. According to FISH analysis, 25% of studied patients were classifies as very low-risk and, interestingly, no one of them showed an Unfavorable Phenotype (only one patient carried CD49d as unique negative marker). In our cohort, 50% of patients were low-risk with no genetic abnormalities or +12, but 63% of them showed an Unfavorable Phenotype with high CD49d and CD38 expression in 100% and 60% of cases, respectively. Our data confirm the independent negative prognostic role of CD49d and suggest a stronger prognostic power compared to CD38 in the definition of CLL outcome, because of its complex activity as homing marker, signaling receptor and anti-apoptotic molecule. Thus, the prognostic significance of CD49d may be enhanced when considered in comparison with other established markers, as CD11c and CD38. In conclusion, our results propose the use of the CD49d marker in combination with other B-cell membrane antigens as an additional tool for routine diagnosis and risk-stratification of CLL patients. Identification of high-risk phenotype with a simple scoring method could improve the treatment of these patients, who could take advantage of the most recent molecular targeting therapies. Disclosures No relevant conflicts of interest to declare.
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- 2016
15. Endocrinopathies after allogeneic and autologous transplantation of hematopoietic stem cells
- Author
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Libuse Tauchmanovà, Giovanna Muscogiuri, Valentina Giudice, Stefano Palomba, Idalucia Ferrara, Annamaria Colao, Bianca Serio, Carmine Selleri, Francesco Orio, Mariarosaria Sessa, Orio, Francesco, Muscogiuri, Giovanna, Palomba, S, Serio, B, Sessa, M, Giudice, V, Ferrara, I, Tauchmanovà, L, Colao, Annamaria, and Selleri, 4.
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Oncology ,Male ,medicine.medical_specialty ,endocrine system ,lcsh:Medicine ,Review Article ,Endocrine System Diseases ,lcsh:Technology ,Transplantation, Autologous ,General Biochemistry, Genetics and Molecular Biology ,Sex Factors ,Risk Factors ,Internal medicine ,Autologous Transplantation ,medicine ,Adrenal insufficiency ,Endocrine system ,Autologous transplantation ,Humans ,Transplantation, Homologous ,lcsh:Science ,Endocrinopathies ,Chronic thyroiditis ,Allogeneic ,General Environmental Science ,Subclinical infection ,lcsh:T ,business.industry ,lcsh:R ,Thyroid ,Hematopoietic Stem Cell Transplantation ,General Medicine ,Total body irradiation ,Hematopoietic Stem Cells ,medicine.disease ,Thyroid Diseases ,Transplantation ,medicine.anatomical_structure ,surgical procedures, operative ,Infertility ,Immunology ,lcsh:Q ,Female ,business ,Hypothalamic Diseases - Abstract
Early and late endocrine disorders are among the most common complications in survivors after hematopoietic allogeneic- (allo-) and autologous- (auto-) stem cell transplant (HSCT). This review summarizes main endocrine disorders reported in literature and observed in our center as consequence of auto- and allo-HSCT and outlines current options for their management. Gonadal impairment has been found early in approximately two-thirds of auto- and allo-HSCT patients: 90–99% of women and 60–90% of men. Dysfunctions of the hypothalamus-pituitary-growth hormone/insulin growth factor-I axis, hypothalamus-pituitary-thyroid axis, and hypothalamus-pituitary-adrenal axis were documented as later complicances, occurring in about 10, 30, and 40–50% of transplanted patients, respectively. Moreover, overt or subclinical thyroid complications (including persistent low-T3 syndrome, chronic thyroiditis, subclinical hypo- or hyperthyroidism, and thyroid carcinoma), gonadal failure, and adrenal insufficiency may persist many years after HSCT. Our analysis further provides evidence that main recognized risk factors for endocrine complications after HSCT are the underlying disease, previous pretransplant therapies, the age at HSCT, gender, total body irradiation, posttransplant derangement of immune system, and in the allogeneic setting, the presence of graft-versus-host disease requiring prolonged steroid treatment. Early identification of endocrine complications can greatly improve the quality of life of long-term survivors after HSCT.
- Published
- 2013
16. Induction Therapy With Continuous Alternate-Day Low Dose Lenalidomide Combined With Low-Dose Prednisone In Octogenarian Multiple Myeloma Patients
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Bianca Serio, M Rocco, Mariarosaria Sessa, G Villani, Idalucia Ferrara, Valentina Giudice, Carmine Selleri, R Fontana, and L Pezzullo
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medicine.medical_specialty ,Aspirin ,Performance status ,business.industry ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Gastroenterology ,Discontinuation ,Surgery ,Zoledronic acid ,Prednisone ,Internal medicine ,Medicine ,business ,Adverse effect ,Multiple myeloma ,Lenalidomide ,medicine.drug - Abstract
About 30% of patients with newly diagnosed multiple myeloma (NDMM) are older than 75 years. Immunomodulatory drugs (IMIDs) have improved response rates and outcomes of NDMM, except for patients older than 75 years more vulnerable to side effects of IMIDs because of their frailty and comorbidities. We evaluated efficacy, toxicity and health-related quality of life (HRQOL) associated with continuous alternate-day low dose lenalidomide (LD-R, 10 mg on alternate days) and low dose prednisone (15 mg/day) (LD-RP) in 7 octogenarian NDMM patients (5 males and 2 females) with a median age of 82 years (range 80-87). All octogenarian patients had IgG MM, except 1 oligosecretory lambda chain MM; all were in Durie-Salmon stage III, except 1 in stage II, and had poor WHO performance status (median: 2, range 1-3). Patients were evaluated at baseline and every 6 months for HRQOL according to MM-specific questionnaire QLQ-MY20 of European Organisation for Research and Treatment of Cancer (EORTC). All patients received aspirin thromboprophylaxis, 57% of them requiring from diagnosis erythropoietin and zoledronic acid treatment. In these 7 octogenarian NDMM patients completing at least three months of therapy, the overall response rate (ORR) was 86%, including 1 complete remission (CR), 2 very good partial remission (VgPR) and 3 PR. After a median follow-up of 12 months (range 3-24), the quality of response improved with continuous LD-RP treatment with a cumulative median reduction in monoclonal protein levels of 85% (range 20-100%); none of the patients required discontinuation of treatment secondary to specific hematologic and/or extra-hematologic toxicity. In addition, QLQ MY-20 questionnaires revealed that 70% of patients treated with continuous LD-RP reported improvements of QOL scores. Two out of 7 octogenarian patients died (1 for progression after 12 months and 1 for sepsis no treatment-related), and 2-year overall survival and progression-free survival estimates were 41% and 75%, respectively. Noteworthy, all patients treated with continuous alternate-day LD-RP showed a progressive increase in the percentage of CD3+ CD56+ NK cells during the first 6 months of LD-RP therapy reaching a plateau maintained until +12 months after initiation of therapy: the median percentage of NK cells was 4% before LD-RP treatment versus 10%, 13%, 30%, 31%, and 27% at +1, +3, +6, +9 and +12 months, respectively. Mean fold increase of NK cells during LD-RP therapy was 1.5, 2.5, and 6.5 at +1, +3 and +6 months, respectively. Progressive increase of NK cells was concomitantly associated with reduction in tumor-linked monoclonal immunoglobulin in all patients and increased circulating NK cells further support that this drug may mediate its anti-MM effect, at least in part by modulating NK-cell number and function. Our data provide evidence that continuous alternate-day low dose lenalidomide is a manageable and effective frontline treatment for octogenarian NDMM patients and increases circulating NK cells. These preliminary results require further validation in prospective larger studies. Disclosures: No relevant conflicts of interest to declare.
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- 2013
17. Accelerated bone mass senescence after hematopoietic stem cell transplantation
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Bianca, Serio, Luca, Pezzullo, Raffaele, Fontana, Silvana, Annunziata, Rosa, Rosamilio, Maria Rosaria Sessa, Valentina Giudice, Idalucia, Ferrara, Monia, Rocco, Gennaro De Rosa, Patrizia, Ricci, Libuse, Tauchmanovà, Nunzia, Montuori, Carmine Selleri, Serio, B, Pezzullo, L, Fontana, R, Annunziata, S, Rosamilio, R, Sessa, M, Giudice, V, Ferrara, I, Rocco, M, DE ROSA, Gennaro, Ricci, P, Tauchmanovà, L, Montuori, Nunzia, and Selleri, C.
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bone mass ,surgical procedures, operative ,immune system diseases ,hemopoietic stem cell transplantation ,Articles ,osteoporosis ,bisphosphonates ,allogeneic bone marrow transplantation - Abstract
Osteoporosis and avascular necrosis (AVN) are long-lasting and debilitating complications of hematopoietic stem cell transplantation (HSCT). We describe the magnitude of bone loss, AVN and impairment in osteogenic cell compartment following autologous (auto) and allogeneic (allo) HSCT, through the retrospective bone damage revaluation of 100 (50 auto- and 50 allo-HSCT) long-term survivors up to 15 years after transplant. Current treatment options for the management of these complications are also outlined. We found that auto- and allo-HSCT recipients show accelerated bone mineral loss and micro-architectural deterioration during the first years after transplant. Bone mass density (BMD) at the lumbar spine, but not at the femur neck, may improve in some patients after HSCT, suggesting more prolonged bone damage in cortical bone. Phalangeal BMD values remained low for even more years, suggesting persistent bone micro-architectural alterations after transplant. The incidence of AVN was higher in allo-HSCT recipients compared to auto-HSCT recipients. Steroid treatment length, but not its cumulative dose was associated with a higher incidence of bone loss. Allo-HSCT recipients affected by chronic graft versus host disease seem to be at greater risk of continuous bone loss and AVN development. Reduced BMD and higher incidence of AVN was partly related to a reduced regenerating capacity of the normal marrow osteogenic cell compartment. Our results suggest that all patients after auto-HSCT and allo-HSCT should be evaluated for their bone status and treated with anti-resorptive therapy as soon as abnormalities are detected.
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