Publications by authors named "Federico Simonetti"

8 Publications

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MAP2K1-driven mixed Langerhans cell histiocytosis, Rosai-Dorfman-Destombes disease and Erdheim-Chester disease, clonally related to acute myeloid leukemia.

J Cutan Pathol 2021 May 24;48(5):637-643. Epub 2020 Nov 24.

Department of Dermatology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.

Mixed histiocytoses are a rare and recently recognized subset of histiocytic disorders that may involve the skin, characterized by the synchronous or metachronous development of lesions with Langerhans and/or non-Langerhans cell histiocytosis histopathological features. Around 10% of patients diagnosed with histiocytosis may develop a hematological malignancy, often with dramatic prognostic consequences. We hereby describe the exceptional case of a patient developing a MAP2K1-driven mixed histiocytosis with Langerhans cell histiocytosis, Rosai-Dorfman-Destombes disease, and Erdheim-Chester disease features and cutaneous involvement, progressing to a fatal and clonally-related acute myeloid leukemia. We reviewed the literature on similar cases and discussed the histopathological difficulties in their diagnosis and their clinical-pathological features.
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http://dx.doi.org/10.1111/cup.13918DOI Listing
May 2021

Ruxolitinib Rapidly Reduces Acute Respiratory Distress Syndrome in COVID-19 Disease. Analysis of Data Collection From RESPIRE Protocol.

Front Med (Lausanne) 2020 4;7:466. Epub 2020 Aug 4.

Hematology Unit, Università of Siena, Azienda Ospedaliero Universitaria Senese, Siena, Italy.

The Coronavirus disease (COVID-19) pandemic is causing millions of infections and hundreds of thousands of deaths worldwide. Cumulative clinical and laboratory evidence suggest that a subset of patients with severe COVID-19 may develop a cytokine storm syndrome during the course of the disease, with severe respiratory impairment requiring ventilatory support. One field of research nowadays is to identify and treat viral-induced hyperinflammation with drugs used in other clinical conditions characterized by an hyperinflammation status. These drugs might help to reduce COVID19 mortality. Ruxolitinib, a JAK1 and JAK2 inhibitor, has been successfully used to treat severe immune-mediated diseases, such as graft vs. host disease and Hemophagocytic lymphohistiocytosis. We used ruxolitinib in 18 patients with clinically progressive COVID-19 related acute respiratory distress syndrome, with a primary endpoint to rapidly reduce the degree of respiratory impairment and as a secondary endpoint to rapidly restore the PaO/FiO ratio, as an evaluation of clinical status, and monitoring of drug related Adverse Events. Parameters of inflammation responses and organ functions were assessed and monitored. The treatment plan was ruxolitinib 20 mg bid for the first 48 h and subsequent two-step de-escalation at 10 mg bid and 5 mg bid for a maximum of 14 days of treatment. Our data collection shows a rapid clinical response with no evolution from to mechanical ventilation in 16/18 patients and no response in two patients (overall response rate-ORR 89%). Already after 48 h of ruxolitinib treatment 16/18 patients showed evident clinical improvement, and after 7 days of treatment 11/18 patients showed fully recovered respiratory function (pO > 98% in spontaneous breathing), 4/18 patients had minimal oxygen requirement (2-4 L/m), 1/18 patient showed stable disease, and 2/18 patient showed progressive disease. After 14 days, 16/18 patients showed complete recovery of respiratory function (ORR 89%). Compliance to ruxolitinib planned treatment was 100% and no serious adverse event was recorded. In our case series of 18 critically ill patients with COVID-19 and ARDS, administration of ruxolitinib resulted in a clinical improvement that concurred to modify the standard course of disease. Ruxolitinib can be a therapeutic option for patients with respiratory insufficiency in COVID-19 related ARDS. RESPIRE Study (uxolitinib for the treatment of acute rratory distss syndrome, ClinicalTrials.gov Identifier: NCT04361903).
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http://dx.doi.org/10.3389/fmed.2020.00466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417512PMC
August 2020

Real-world experience with decitabine as a first-line treatment in 306 elderly acute myeloid leukaemia patients unfit for intensive chemotherapy.

Hematol Oncol 2019 Oct 20;37(4):447-455. Epub 2019 Aug 20.

UO Ematologia e Trapianto Midollo Osseo, IRCCS Istituto Scientifico Universitario San Raffaele, Milan, Italy.

Despite widespread use of decitabine to treat acute myeloid leukaemia (AML), data on its effectiveness and safety in the real-world setting are scanty. Thus, to analyze the performance of decitabine in clinical practice, we pooled together patient-level data of three multicentric observational studies conducted since 2013 throughout Italy, including 306 elderly AML patients (median age 75 years), unfit for intensive chemotherapy, treated with first-line decitabine therapy at the registered schedule of 20 mg/m /iv daily for 5 days every 4 weeks. Overall response rate (ORR), overall survival (OS) curves, and multivariate hazard ratios (HRs) of all-cause mortality were computed. Overall, 1940 cycles of therapy were administered (median, 5 cycles/patient). A total of 148 subjects were responders and, therefore, ORR was 48.4%. Seventy-one patients (23.2%) had complete remission, 32 (10.5%) had partial remission, and 45 (14.7%) had haematologic improvement. Median OS was 11.6 months for patients with favourable-intermediate cytogenetic risk and 7.9 months for those with adverse cytogenetic risk. Median relapse-free survival after CR was 10.9 months (95% confidence interval [CI]: 8.7-16.0). In multivariate analysis, mortality was higher in patients with adverse cytogenetic risk (HR=1.58; 95% CI: 1.13-2.21) and increased continuously with white blood cell (WBC) count (HR=1.12; 95% CI: 1.06-1.18). A total of 183 infectious adverse events occurred in 136 patients mainly (>90%) within the first five cycles of therapy. This pooled analysis of clinical care studies confirmed, outside of clinical trials, the effectiveness of decitabine as first-line therapy for AML in elderly patients unfit for intensive chemotherapy. An adverse cytogenetic profile and a higher WBC count at diagnosis were, in this real life setting, unfavourable predictors of survival.
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http://dx.doi.org/10.1002/hon.2663DOI Listing
October 2019

Oral gentamicin therapy for Carbapenem-resistant Klebsiella pneumoniae gut colonization in hematologic patients: a single center experience.

New Microbiol 2017 Jul 17;40(3):161-164. Epub 2017 May 17.

Nuovo Santa Chiara Hospital, Cisanello, Infectious Disease Unit, Pisa, Italy.

The mortality for carbapenem-resistant Klebsiella pneumoniae (KPC-Kp) infection ranges from 18 to 48% depending on the type of therapy. Mortality rates in hematologic patients are even higher, up to 85%. Gut decontamination with oral gentamicin might be an option to avoid a subsequent KPC-Kp infection in colonized patients. We treated 14 hematologic patients with oral gentamicin, 80 mg four times daily, for 7 to 25 days in order to eradicate KPC-Kp from the gut, starting oral gentamicin therapy when possible after the discontinuation of systemic antibiotic therapy. The overall decontamination rate in the entire study population was 71% (10/14). Out of the 4 patients who did not respond to oral gentamicin therapy, 1 KPC-Kp strain was gentamicin resistant and 4 patients received concomitant systemic antibiotic therapy (CSAT). One of these patients died from KPC-Kp sepsis. The decontamination rate was 90% (9/10) in patients receiving oral gentamicin only, versus 25% (1/4) in those also treated with CSAT. No new gentamicin-resistant KPC-Kp strain was isolated during oral gentamicin therapy Oral gentamicin might be useful for gut decontamination and prevention of KPC-Kp infection. This option should be considered in patients colonized by a gentamicin-susceptible KPC-Kp strain and not receiving CSAT.
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July 2017

Management of anaemia in oncohaematological patients treated with biosimilar epoetin alfa: results of an Italian observational, retrospective study.

Ther Adv Med Oncol 2017 Jan 22;9(1):22-32. Epub 2016 Oct 22.

Versilia Azienda ULSS 12, Lido di Camaiore, Italy.

Background: Many patients with solid tumours or nonmyeloid haematopoietic tumours develop symptomatic anaemia, which has a major impact on quality of life (QoL). The efficacy of erythropoiesis-stimulating agents (ESAs) in improving QoL and reducing blood transfusions has been widely demonstrated. Binocrit® (biosimilar epoetin alfa) is an ESA indicated in the European Union for treating chemotherapy-induced anaemia. The aim of this study was to investigate the effect of Binocrit® on haemoglobin (Hb) levels in anaemic cancer patients in Italian clinical practice.

Methods: The ANEMONE study was a national, longitudinal, retrospective, multicentre observational study. Patients had to be 18 years or older, with a solid tumour or non-Hodgkin's lymphoma, Hodgkin's disease or multiple myeloma, receiving chemotherapy, and treated with Binocrit® to manage chemotherapy-induced anaemia. The primary outcomes were the proportion of patients with a Hb increase ⩾1 g/dl during the first 4 weeks and with a Hb increase ⩾2 g/dl during the first 12 weeks.

Results: A total of 245 patients were enrolled and 215 patients were evaluable for statistical analysis. In the first 4 weeks, 49.3% of patients showed an increase in Hb of ⩾1 g/dl: 45.5% in patients with solid tumours and 52.1% in patients with haematological malignancies. In the first 12 weeks, 51.6% of patients showed an increase in Hb of ⩾2 g/dl (48.4% solid tumours, 54.2% haematological diseases). Treatment with Binocrit® was well tolerated.

Conclusions: These results confirm the effectiveness and safety of Binocrit® for chemotherapy-induced anaemia in routine practice in patients with solid tumours, lymphoma and myeloma.
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http://dx.doi.org/10.1177/1758834016670554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5298451PMC
January 2017

Personal history and quality of life in chronic myeloid leukemia patients: a cross-sectional study using narrative medicine and quantitative analysis.

Support Care Cancer 2016 11 3;24(11):4487-93. Epub 2016 Jun 3.

Department of Cellular Biotechnologies and Hematology, Sapienza University, Via Benevento 6, 00161, Rome, Italy.

Background: Tyrosine kinase inhibitors (TKIs) drastically changed the outcome of patients diagnosed with chronic myeloid leukemia (CML). Several reports indicated the advantage of continue long-term adherence associated with positive outcome. Therefore, it is important to better understand from the patient's standpoint the experience of living with the disease and the related treatment.

Objectives: In this study, quantitative analysis and narrative medicine were combined to get insights on this issue in a population of 257 patients with CML in chronic phase treated with TKIs (43 % men, with a median age of 58 years, 27 % aged 31-50 years), followed for a median time of 5 years. Sixty-one percent of patients enrolled were treated in first line, whereas 37 % were treated in second line.

Results: The results showed more positive perceptions and acceptance in males compared to females, without impact of disease on relationships. Level of positive acceptance was more evident in elderly compared to younger patients, with a close connection with median time from diagnosis. Overall, female patients reported negative perceptions and an impact of disease on family daily living. The majority of patients understood the importance of continue adherence to treatment, with 27 % resulting less adherent (60 % for forgetfulness), even if well informed and supported by his/her physician.

Discussion And Conclusions: Narrative medicine, in association to quantitative analysis, can help physicians to understand needs of their patients in order to improve communication.
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http://dx.doi.org/10.1007/s00520-016-3286-zDOI Listing
November 2016

Thrombopoietin receptor agonists for preparing adult patients with immune thrombocytopenia to splenectomy: results of a retrospective, observational GIMEMA study.

Am J Hematol 2016 May 4;91(5):E293-5. Epub 2016 Apr 4.

Clinica Ematologica, DISM, a O U S. M. Misericordia, Udine, Italy.

In patients with immune thrombocytopenia (ITP) refractory to corticosteroids and intravenous immunoglobulins (IVIG), splenectomy may result at higher risk of peri-operative complications and, for this reason, potentially contraindicated. The thrombopoietin receptor agonists (TPO-RAs) romiplostim and eltrombopag have shown high therapeutic activity in primary ITP, but data of efficacy and safety regarding their use in preparation for splenectomy are missing. Thirty-one adult patients, median age 50 years, with corticosteroids and/or IVIG refractory persistent and chronic ITP who were treated with TPO-RAs (romiplostim= 24; eltrombopag= 7) with the aim to increase platelet count and allow a safer execution of splenectomy were retrospectively evaluated. Twenty-four patients (77%) responded to the use of TPO-RAs with a median platelet count that increased from 11 × 10(9) /L before starting TPO-RAs to 114 × 10(9) /L pre-splenectomy, but a concomitant treatment with corticosteroids and/or IVIG was required in 19 patients. Twenty-nine patients underwent splenectomy while two patients who responded to TPO-RAs subsequently refused surgery. Post-splenectomy complications were characterized by two Grade 3 thrombotic events (1 portal vein thrombosis in the patient with previous history of HCV hepatitis and 1 pulmonary embolism), with a platelet count at the time of thrombosis of 260 and 167 × 10(9) /L, respectively and one Grade 3 infectious event. TPO-RAs may represent a therapeutic option to improve platelet count and reduce the risk of peri-operative complications in ITP candidates to splenectomy. An increased risk of post-splenectomy thromboembolic events cannot be ruled out and thromboprophylaxis with low-molecular weight heparin is generally recommended.
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http://dx.doi.org/10.1002/ajh.24341DOI Listing
May 2016

Cytarabine and clofarabine after high-dose cytarabine in relapsed or refractory AML patients.

Am J Hematol 2012 Dec 1;87(12):1047-51. Epub 2012 Aug 1.

Hematology Section, Careggi hospital and University of Florence, Florence, Italy.

Clofarabine has been shown to be effective in AML patients, either as single agent or, mainly, in association with intermediate dose cytarabine. Based on these reports, we conducted a preliminary study combining clofarabine and intermediate dose cytarabine in AML patients who relapsed or failed to respond to at least two induction therapies. We treated 47 patients affected by relapsed/refractory AML with a regimen including clofarabine at 22.5 mg/m(2) daily on days 1-5, followed after 3 hr by cytarabine at 1 g/m(2) daily on days 1-5. Ten patients received a further consolidation cycle with clofarabine at 22.5 mg/m(2) and cytarabine at 1 g/m(2) day 1-4. Among the 47 patients, 24/47 (51%) achieved a complete remission, 5/47 (10.5%) a partial response, 10/47 (21%) had a resistant disease, and 6/47 (13%) died of complications during the aplastic phase. The most frequent nonhematologic adverse events were vomiting, diarrhea, transient liver toxicity, febrile neutropenia, and infections microbiologically documented. Among the 24 patients who obtained a CR 13 underwent allogeneic bone marrow transplantation. In 14 patients, complete remission duration was shorter than 12 months, whereas 10 patients experienced longer complete remission duration. These very preliminary results suggest that clofarabine-cytarabine regimen is effective in this particularly poor prognosis category of patients, representing a potential "bridge" toward bone marrow transplant procedures. Safety data were consistent with previously reported salvage therapies. Further studies and a longer follow up are warranted.
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http://dx.doi.org/10.1002/ajh.23308DOI Listing
December 2012