Publications by authors named "Davide Facchinelli"

15 Publications

  • Page 1 of 1

Primary Pancreatic Lymphoma: Recommendations for Diagnosis and Management.

J Blood Med 2021 5;12:257-267. Epub 2021 May 5.

Hematology and Bone Marrow Transplant Unit, Department of Medicine, University of Verona, Verona, Italy.

Background: Primary pancreatic lymphoma (PPL) is a rare disease representing 0.1% of all malignant lymphomas, which lacks well-defined diagnostic and therapeutic protocols. We conducted a systematic review to analyze demographic, diagnostic and therapeutic features of PPL.

Methods: This review identified small series and single case reports. Sources were MEDLINE, PubMed, and the Cochrane library from January 2001 to December 2020. Data were screened, extracted and the risk of bias analyzed by three independent reviewers.

Results: A total of 107 eligible papers (17 small series, 90 single case reports) describing 266 patients were identified. Patients had a median age of 53.1 (range 3-86) years and were males in 64.6% of cases. Abdominal pain and jaundice were the most common presenting symptoms, affecting 75.3% and 41.8% of patients, respectively. PPL had a median size of 60.6 mm (range 16-200) and it was localized in the pancreatic head in 63.7% of cases. At diagnosis most patients underwent ultrasonography followed by computed tomography. PPL typically showed low echogenicity, and lower contrast enhancement than solid tumors. Histopathological specimens were obtained by percutaneous or endoscopic biopsies in 47.7% of patients; abdominal surgery was performed in 33.5% of cases. Overall, diffuse large B-cell lymphoma was the most frequent histological diagnosis (53.6%). However, patients aged <18 years were affected by Burkitt lymphoma in 52.4% of cases. Most patients (53.6%) received immunochemotherapy (IC) or IC plus radiotherapy (14%). Demolitive surgery appeared to be associated with impaired survival. Central nervous system (CNS) relapse or progression was observed in 20% of patients.

Conclusion: PPL is a rare entity, with some peculiar features at modern imaging. For diagnostic purposes percutaneous or endoscopic biopsies might be preferable, as opposed to surgery. No definite data is available about the optimal treatment, which should be tailored on the histological type and associated with CNS prophylaxis.
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http://dx.doi.org/10.2147/JBM.S273095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107008PMC
May 2021

Isolated cerebellar progressive multifocal leukoencephalopathy after allogeneic bone marrow transplantation: focus on imaging.

Tumori 2021 Feb 25:300891621997920. Epub 2021 Feb 25.

Neuroradiology Unit, Department of Diagnostics, San Bortolo Hospital, Vicenza, Italy.

Introduction: Progressive multifocal leukoencephalopathy (PML) is caused by JC virus opportunistic infection in the setting of immunodeficiency. Typical imaging features are multifocal and asymmetric lesions within supratentorial subcortical white matter in parieto-occipital regions.

Case Description: A 47-year-old patient experienced a relapse of acute myeloid leukemia 21 months after hematopoietic stem cell transplantation. He also had visual impairment and magnetic resonance imaging showed an isolated cerebellar lesion without mass effect or enhancement. Common opportunistic infections and leukemic central nervous system involvement were excluded by cerebrospinal fluid (CSF) analysis. Given the worsening clinical and radiologic scenario, PML was suspected, and CSF protein chain reaction analysis was positive for JC virus.

Conclusions: Given its potential curability, PML should be thoroughly investigated in patients with hematologic neoplasms and atypical isolated cerebellar presentation.
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http://dx.doi.org/10.1177/0300891621997920DOI Listing
February 2021

Infections in patients with lymphoproliferative diseases treated with targeted agents: SEIFEM multicentric retrospective study.

Br J Haematol 2021 Apr 15;193(2):316-324. Epub 2020 Oct 15.

Institute of Hematology, Fondazione Policlinico A. Gemelli - IRCCS -Università Cattolica S. Cuore, Roma, Italy.

We describe the opportunistic infections occurring in 362 patients with lymphoproliferative disorders treated with ibrutinib and idelalisib in clinical practice. Overall, 108 of 362 patients (29·8%) developed infections, for a total of 152 events. Clinically defined infections (CDI) were 49·3% (75/152) and microbiologically defined infections (MDI) were 50·7% (77/152). Among 250 patients treated with ibrutinib, 28·8% (72/250) experienced one or more infections, for a total of 104 episodes. MDI were 49% (51/104). Bacterial infections were 66·7% (34/51), viral 19·6% (10/51) and invasive fungal diseases (IFD) 13·7% (7/51). Among the 112 patients treated with idelalisib, 32·1% (36/112) experienced one or more infections, for a total of 48 episodes. MDI were 54·2% (26/48). Bacterial infections were 34·6% (9/26), viral 61·5% (16/26) and IFD 3·8% (1/26). With ibrutinib, the rate of bacterial infections was significantly higher compared to idelalisib (66·7% vs. 34·6%; P = 0·007), while viral infections were most frequent in idelalisib (61·5% vs. 19·6%; P < 0·001). Although a higher rate of IFD was observed in patients treated with ibrutinib, the difference was not statistically significant (13·7% vs. 3·8% respectively; P = 0·18). Bacteria are the most frequent infections with ibrutinib, while viruses are most frequently involved with idelalisib.
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http://dx.doi.org/10.1111/bjh.17145DOI Listing
April 2021

Prognostic models integrating quantitative parameters from baseline and interim positron emission computed tomography in patients with diffuse large B-cell lymphoma: post-hoc analysis from the SAKK38/07 clinical trial.

Hematol Oncol 2020 Dec 4;38(5):715-725. Epub 2020 Oct 4.

Institute of Oncology Research, Università della Svizzera italiana, Bellinzona, Switzerland.

Positron emission computed tomography (PET/CT) in patients with diffuse large B-cell lymphoma (DLBCL) enrolled in a prospective clinical trial were reviewed to test the impact of quantitative parameters from interim PET/CT scans on overall (OS) and progression-free (PFS) survival. We centrally reviewed baseline and interim PET/CT scans of 138 patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone given every 14 days (R-CHOP14) in the SAKK38/07 trial (ClinicalTrial.gov identifier: NCT00544219). Cutoff values for maximum standardized uptake value (SUV ), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and metabolic heterogeneity (MH) were defined by receiver operating characteristic analysis. Responses were scored using the Deauville scale (DS). Patients with DS 5 at interim PET/CT (defined by uptake >2 times higher than in normal liver) had worse PFS (P = 0.014) and OS (P < 0.0001). A SUV reduction (Δ) greater than 66% was associated with longer PFS (P = 0.0027) and OS (P < 0.0001). Elevated SUV , MTV, TLG, and MH at interim PET/CT also identified patients with poorer outcome. At multivariable analysis, ΔSUV and baseline MTV appeared independent outcome predictors. A prognostic model integrating ΔSUV and baseline MTV discriminated three risk groups with significantly (log-rank test for trend, P < 0.0001) different PFS and OS. Moreover, the integration of MH and clinical prognostic indices could further refine the prediction of OS. PET metrics-derived prognostic models perform better than the international indices alone. Integration of baseline and interim PET metrics identified poor-risk DLBCL patients who might benefit from alternative treatments.
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http://dx.doi.org/10.1002/hon.2805DOI Listing
December 2020

Primary pancreatic lymphoma: Clinical presentation, diagnosis, treatment, and outcome.

Eur J Haematol 2020 Oct 2;105(4):468-475. Epub 2020 Jul 2.

Hematology Unit, Department of Medicine, University of Verona, Verona, Italy.

Primary pancreatic lymphoma (PPL) is a rare disease representing 0.1% of malignant lymphomas, which lacks well-defined diagnostic and therapeutic protocols.

Objectives: To describe PPL clinical, diagnostic and histological characteristics, together with therapy and outcome, in a relatively large series of patients.

Methods: The study includes 39 PPL patients, aged ≥15 years, observed from January 2005 to December 2018, in 8 Italian Institutions.

Results: The main symptoms were abdominal pain (58%) and jaundice (47%). Lactate dehydrogenase serum levels were elevated in 43% of patients. Histological specimens were mostly obtained by percutaneous (41%) or endoscopic (36%) biopsy, with diffuse large B-cell lymphoma being the most frequent (69%) histological diagnosis. Chemotherapy was administered alone in 65% of patients, with radiotherapy in 17%, or after surgery in 9%. The 2-year overall survival (OS) was 62%, the 2-year progression-free survival (PFS) 44%. Debulking surgery (with or without chemotherapy) was associated with a significant worse OS. Three (9.4%) of 32 high-grade patients experienced a central nervous system (CNS) relapse.

Conclusions: PPL is rare, often high-grade, with symptoms and localization similar to other pancreatic malignancies. Biopsy should be the preferred diagnostic method. High-grade PPL should undergo CNS prophylaxis.
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http://dx.doi.org/10.1111/ejh.13468DOI Listing
October 2020

Sciatic pain by neurolymphomatosis as initial presentation of disseminated diffuse large B cell lymphoma involving the testis and the CNS.

Hematol Oncol 2020 Apr 5;38(2):197-200. Epub 2020 Feb 5.

Oncology Institute of Southern Switzerland (IOSI), Medical Oncology, Imaging Institute of Southern Switzerland, Bellinzona, Switzerland.

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http://dx.doi.org/10.1002/hon.2698DOI Listing
April 2020

Is triple-positive serology for Epstein-Barr virus (VCA-IgG, VCA-IgM, EBNA-IgG) a specific feature of angioimmunoblastic T-cell lymphoma?

Tumori 2020 Oct 21;106(5):424-426. Epub 2019 Oct 21.

Section of Hematology, Department of Medicine, University of Verona and Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy.

Purpose: We assessed the frequency of triple-positive serology (viral capsid antigen [VCA]-immunoglobulin G [IgG], VCA-immunoglobulin M, Epstein-Barr nuclear antigen-IgG) for Epstein-Barr virus (EBV) in a small number of patients with angioimmunoblastic T-cell lymphoma (AITL) at disease onset.

Methods: Nine patients with newly diagnosed AITL were retrospectively enrolled in the present study. For all of them, EBV serology data were available.

Results: Of 9 patients, 7 (77.7%) had a triple-positive serology (VCA-IgG, VCA-IgM, EBNA-IgG ) for EBV. These patients were characterized by bone marrow involvement, high incidence of thrombocytopenia, and poor prognosis according to Revised International Prognostic Index and Prognostic Index for Angioimmunoblastic T-cell Lymphoma scores.

Conclusion: Assessment of both viremia and serology for EBV could be useful in patients with clinical and laboratory data suggesting lymphoma diagnosis; furthermore, although our data need to be validated in a larger cohort of patients, triple positivity for EBV serology might help to direct the diagnosis toward AITL.
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http://dx.doi.org/10.1177/0300891619882504DOI Listing
October 2020

Efficacy and toxicity of Decitabine in patients with acute myeloid leukemia (AML): A multicenter real-world experience.

Leuk Res 2019 01 28;76:33-38. Epub 2018 Nov 28.

Clinica Ematologica, Centro Trapianti e Terapie Cellulari, Azienda Sanitaria Universitaria Integrata, Udine, Italy.

Background: The hypomethylating agent Decitabine (DAC) is a valuable treatment option in acute myeloid leukemia (AML), particularly in elderly patients (pts) not suitable for intensive chemotherapy (CHT). However, limited data are available about efficacy and safety of DAC in clinical practice.

Patients And Methods: We retrospectively reviewed data of 104 AML pts treated with DAC in eight Italian Hematological Centers from 2015 to 2017. The objective of this study was to evaluate the efficacy and safety of DAC in older AML pts outside of clinical trial. Seventy-five (75%) pts received DAC as first line treatment (Cohort 1) and 29 pts as salvage therapy (Cohort 2). All pts received a DAC schedule of 20 mg/sqm IV for 5-days, every 28 days. The median age was 72.5 years (74 in cohort 1 and 66 in cohort 2) and 16% of pts had an ECOG performance status >2 at the start of DAC treatment (with non-significant difference in the two cohorts). The cumulative illness rating scale (CIRS) was > 6 in 27% of pts. Forty-five pts (43%) had secondary AML. Bone marrow blast count was > 30% in 64% of patients (67/104). In the relapsed cohort 17/29 (59%) patients were treated with DAC after conventional CHT, 5/29 (17%) after allo-SCT and 7/29 (24%) after azacitidine therapy.

Results: A total of 469 DAC cycles were given to the 104 pts with a median of 3 cycles (range 1-21) and 45/104 (43%) pts received > 4 cycles. The Overall Response Rate (ORR = Complete Remission-CR plus Partial Remission-PR) was 33%, significantly higher in Cohort 1 (42%) compared to Cohort 2 (14%) (p = 0.009). The median duration of response was 6 months (range 1-20). In Cohort 1 the best response (CR or PR) was obtained between 3th and 6th cycle. In multivariate Cox regression analysis, achievement of CR or PR (HR = 0.78; p = 0.0004), CIRS < 6 (HR = 0.9; p = 0.04) and complex karyotype (HR = 0.8; p = 0.03) were significant predictors of better overall survival (OS). Median OS from the start of DAC therapy was 11 months for the whole population with a significant OS advantage in Cohort 1 (median OS 12.7 mths vs 6.3 mths; p = 0.003); median OS was significantly longer in responders compared to non-responders (22.6 mths vs 5.7 mths; p < 0.0001). At the last follow-up, 56 patients (54%) are still alive and 48 (46%) are dead (71% due to disease progression). The most common toxicities were myelosuppression and documented infectious complications that occurred mainly during the first 4 cycles.

Conclusion: These data confirm the efficacy (ORR 33%) and the acceptable safety profile of DAC in the real life management of AML in elderly pts unsuitable for intensive CHT, with a significant better performance in first line therapy (ORR 42%, median OS 12.7 mths). The efficacy of DAC, both in first line and as salvage therapy, may probably be improved with combined treatment strategies and/or with different DAC schedules that could increase its anti-leukemic effect.
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http://dx.doi.org/10.1016/j.leukres.2018.11.015DOI Listing
January 2019

Invasive Fungal Infections in Patients with Chronic Lymphoproliferative Disorders in the Era of Target Drugs.

Mediterr J Hematol Infect Dis 2018 1;10(1):e2018063. Epub 2018 Nov 1.

Institute of Haematology, Fondazione Policlinico A. Gemelli- IRCCS- Università Cattolica S. Cuore, Rome, Italy.

This review summarizes the more recent evidence about epidemiology and risk factors for invasive fungal infections (IFI) in patients affected by Chronic Lymphocytic Leukemia (CLL), indolent Non Hodgkin Lymphoma (iNHL) and Multiple Myeloma (MM). Despite advances in the prognosis and treatment of hematological malignancies in recent years, susceptibility to infection remains a significant challenge to patient care. A large amount of data regarding patients with acute leukemia has been published while little information is available on the incidence of IFI in chronic lymphoproliferative disorders (CLD). New drugs are now available for treatment of lymphoproliferative disorders which may cause suppression of humoral immunity, cellular immunity, and deficiency of white blood cells, increasing the risk for infections which remain the leading cause of mortality in these patients.
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http://dx.doi.org/10.4084/MJHID.2018.063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6223569PMC
November 2018

Primary sphenoid lymphoma: Focus on imaging.

Tumori 2018 Dec 1;104(6):NP42-NP45. Epub 2018 Oct 1.

1 Department of Medicine, Section of Hematology, University of Verona, Verona, Italy.

Primary lymphoma of the sphenoid is an extremely rare pathology, therefore it is difficult to hypothesize and the imaging characteristics are not well-known. Here we report the imaging features in computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) scan of a 44-year-old patient who presented with severe headache. CT and MRI showed a sphenoid sinus mass that suggested rhinopharyngeal lesion or a chordoma. However, biopsy from the mass histologically proved it to be Diffuse large B-cell lymphoma and PET examinations revealed increased fluorodeoxyglucose uptake around the sphenoid bone and multiple spinal lesions.
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http://dx.doi.org/10.1177/0300891618803501DOI Listing
December 2018

CT imaging of primary pancreatic lymphoma: experience from three referral centres for pancreatic diseases.

Insights Imaging 2018 Feb 15;9(1):17-24. Epub 2018 Jan 15.

Department of Radiology, Policlinico G. B. Rossi, University of Verona, Verona, Italy.

Purpose: To describe CT characteristics of primary pancreatic lymphoma (PPL), a rare disease with features in common with adenocarcinoma.

Materials And Methods: Fourteen patients were enrolled. CT: unenhanced scan, contrast-enhanced pancreatic and venous phases. Image analysis: tumour location; peri-pancreatic vessel encasement; necrosis; enlarged lymph nodes; fat stranding; enlarged bile duct and pancreatic duct; neoplasm longest dimension, volume and density.

Results: Histopathological diagnoses: follicular non-Hodgkin lymphoma (5/14), diffuse large B-cell lymphoma (6/14) and high-grade B-cell lymphoma not otherwise specified (3/14). Six of 14 PPLs were located in the pancreatic head and 7/14 in the body-tail; 1/14 involved the whole gland. In 5/14 cases the superior mesenteric artery and vein were encased; splenic vein and artery encasement was depicted in 2 PPLs. Necrosis was present in 2/14. Enlarged retroperitoneal lymph nodes were found in 11 cases and fat stranding in all patients. The bile duct was dilated in six cases and the pancreatic duct in five. Mean neoplasm longest diameter and volume were 8.05 cm and 210.8 cm. Mean tumour attenuation values were 39.1 HU at baseline, 60.6 HU in the pancreatic phase and 71.4 HU in the venous phase.

Conclusions: PPL presents as a large mass lesion with delayed homogeneous enhancement; peri-pancreatic fat stranding and vessel encasement are present, without vascular infiltration. Pancreatic duct dilatation is rare.

Key Points: • Primary pancreatic lymphoma (PPL) is a rare haematological disease • PPL presents imaging features in common with pancreatic carcinoma but also some distinctive findings • The majority of PPLs are large lesions with delayed homogeneous enhancement • Peri-pancreatic fat stranding and vessel encasement are common in PPL • Vascular infiltration and pancreatic duct dilatation are rare in PPL.
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http://dx.doi.org/10.1007/s13244-017-0585-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5825312PMC
February 2018

Blood smear, a key diagnostic tool in hematology: Lessons from two cases of acute hemolysis in previously undiagnosed G6PD deficiency.

Am J Hematol 2016 Nov 11;91(11):1165-1166. Epub 2016 May 11.

Section of Internal Medicine, Department of Medicine, University of Verona and Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy.

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http://dx.doi.org/10.1002/ajh.24385DOI Listing
November 2016

Identification of granulocytic myeloid-derived suppressor cells (G-MDSCs) in the peripheral blood of Hodgkin and non-Hodgkin lymphoma patients.

Oncotarget 2016 May;7(19):27676-88

Department of Medicine, Section of Hematology and Bone Marrow Transplant Unit, University of Verona, Verona, Italy.

Human granulocytic myeloid-derived suppressor cells (G-MDSCs) have been described as low-density immunosuppressive CD66b+CD33dimHLA-DR-granulocytes that co-purify with mononuclear cells after density gradient centrifugation of blood from cancer patients. The role of G-MDSCs in Hodgkin (HL) and non-Hodgkin lymphoma (NHL) remains unclear.The percentage and immunophenotype of CD66b+CD33dimHLA-DR-cells were analyzed in PBMCs from HL and B-cell NHL patients (n = 124) and healthy donors (n = 48). The immunosuppressive functions of these cells were tested in vitro. Correlations between CD66b+CD33dimHLA-DR-cells and patient clinicopathological features and outcome, were evaluated.CD66b+CD33dimHLA-DR-cells were increased in PBMCs from HL and B-cell NHL patients as compared to healthy donors: 2.18 (0.02-70.92) vs 0.42 (0.04-2.97), p < 0.0001. Their percentage remained significantly higher even considering HL (n = 31), indolent (n = 31) and aggressive (n = 62) B-cell NHL patients separately: 1.54 (0.28-26.34), 2.15 (0.02-20.08), and 2.96 (0.25-70.92), respectively, p < 0.0001. CD66b+CD33dimHLA-DR-cells in patient PBMCs were mostly composed of mature CD11b+CD16+ low-density neutrophils in an activated status, as revealed by their higher CD11b and CD66b expression as compared to conventionally isolated (normal-density) autologous or healthy donor neutrophils. The in vitro depletion of CD66b+ cells from patient PBMCs restored the proliferation of autologous T cells. Higher frequencies of CD66b+CD33dimHLA-DR- G-MDSCs correlated significantly with unfavorable prognostic index scores and a shorter freedom from disease progression.PBMCs from HL and B-cell NHL patients contain a population of CD66b+CD33dimHLA-DR- G-MDSCs, mostly composed of activated low-density neutrophils with immunosuppressive properties. These findings disclose a previously unknown G-MDSC-mediated mechanism of immune-escape in lymphomas, therefore anticipating possible targets for therapeutic interventions.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053680PMC
http://dx.doi.org/10.18632/oncotarget.8507DOI Listing
May 2016