Publications by authors named "Alessandro Re"

71 Publications

Engineered Producing Palmitoylethanolamide (PEA) Prevents Colitis in Mice.

Int J Mol Sci 2021 Mar 14;22(6). Epub 2021 Mar 14.

Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, 00185 Rome, Italy.

Palmitoylethanolamide (PEA) is an -acylethanolamide produced on-demand by the enzyme -acylphosphatidylethanolamine-preferring phospholipase D (NAPE-PLD). Being a key member of the larger family of bioactive autacoid local injury antagonist amides (ALIAmides), PEA significantly improves the clinical and histopathological stigmata in models of ulcerative colitis (UC). Despite its safety profile, high PEA doses are required in vivo to exert its therapeutic activity; therefore, PEA has been tested only in animals or human biopsy samples, to date. To overcome these limitations, we developed an NAPE-PLD-expressing (pNAPE-LP), able to produce PEA under the boost of ultra-low palmitate supply, and investigated its therapeutic potential in a murine model of UC. The coadministration of pNAPE-LP and palmitate led to a time-dependent release of PEA, resulting in a significant amelioration of the clinical and histological damage score, with a significantly reduced neutrophil infiltration, lower expression and release of pro-inflammatory cytokines and oxidative stress markers, and a markedly improved epithelial barrier integrity. We concluded that pNAPE-LP with ultra-low palmitate supply stands as a new method to increase the in situ intestinal delivery of PEA and as a new therapeutic able of controlling intestinal inflammation in inflammatory bowel disease.
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http://dx.doi.org/10.3390/ijms22062945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999950PMC
March 2021

Simplified Geriatric Assessment in Older Patients With Diffuse Large B-Cell Lymphoma: The Prospective Elderly Project of the Fondazione Italiana Linfomi.

J Clin Oncol 2021 Apr 12;39(11):1214-1222. Epub 2021 Feb 12.

Division of Medical Oncology and Immune-related Tumors, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano (PN), Italy.

Purpose: To prospectively validate the use of a simplified geriatric assessment (sGA) at diagnosis and to integrate it into a prognostic score for older patients with diffuse large B-cell lymphoma (DLBCL).

Methods: We conducted the prospective Elderly Project study on patients with DLBCL older than 64 years who underwent our Fondazione Italiana Linfomi original geriatric assessment (oGA) (age, Cumulative Illness Rating Scale for Geriatrics, activities of daily living, and instrumental activities of daily living) before treatment. Treatment choice was left to the physician's discretion. The primary end point was overall survival (OS) (ClinicalTrials.gov identifier: NCT02364050).

Results: We analyzed 1,163 patients (median age 76 years), with a 3-year OS of 65% (95% CI, 62 to 68). Because at multivariate analysis on oGA, age > 80 years retained an independent correlation with OS, we also developed a new, simplified version of the GA (sGA) that classifies patients as fit (55%), unfit (28%), and frail (18%) with significantly different 3-year OS of 75%, 58%, and 43%, respectively. The sGA groups, International Prognostic Index, and hemoglobin levels were independent predictors of OS and were used to build the Elderly Prognostic Index (EPI). Three risk groups were identified: low (23%), intermediate (48%), and high (29%), with an estimated 3-year OS of 87% (95% CI, 81 to 91), 69% (95% CI, 63 to 73), and 42% (95% CI, 36 to 49), respectively. The EPI was validated using an independent external series of 328 cases.

Conclusion: The Elderly Project validates sGA as an objective tool to assess fitness status and defines the new EPI to predict OS of older patients with DLBCL.
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http://dx.doi.org/10.1200/JCO.20.02465DOI Listing
April 2021

MATRix-RICE therapy and autologous haematopoietic stem-cell transplantation in diffuse large B-cell lymphoma with secondary CNS involvement (MARIETTA): an international, single-arm, phase 2 trial.

Lancet Haematol 2021 Feb;8(2):e110-e121

Department of Haematology, University College Hospital, London, UK.

Background: Secondary CNS lymphoma is a rare but potentially lethal event in patients with diffuse large B-cell lymphoma. We aimed to assess the activity and safety of an intensive, CNS-directed chemoimmunotherapy consolidated by autologous haematopoietic stem-cell transplantation (HSCT) in patients with secondary CNS lymphoma.

Methods: This international, single-arm, phase 2 trial was done in 24 hospitals in Italy, the UK, the Netherlands, and Switzerland. Adults (aged 18-70 years) with histologically diagnosed diffuse large B-cell lymphoma and CNS involvement at the time of primary diagnosis or at relapse and Eastern Cooperative Oncology Group Performance Status of 3 or less were enrolled and received three courses of MATRix (rituximab 375 mg/m, intravenous infusion, day 0; methotrexate 3·5 g/m, the first 0·5 g/m in 15 min followed by 3 g/m in a 3 h intravenous infusion, day 1; cytarabine 2 g/m every 12 h, in 1 h intravenous infusions, days 2 and 3; thiotepa 30 mg/m, 30 min intravenous infusion, day 4) followed by three courses of RICE (rituximab 375 mg/m, day 1; etoposide 100 mg/m per day in 500-1000 mL over a 60 min intravenous infusion, days 1, 2, and 3; ifosfamide 5 g/m in 1000 mL in a 24 h intravenous infusion with mesna support, day 2; carboplatin area under the curve of 5 in 500 mL in a 1 h intravenous infusion, day 2) and carmustine-thiotepa and autologous HSCT (carmustine 400 mg/m in 500 mL glucose 5% solution in a 1-2 h infusion, day -6; thiotepa 5 mg/kg in saline solution in a 2 h infusion every 12 h, days -5 and -4). The primary endpoint was progression-free survival at 1 year. Overall and complete response rates before autologous HSCT, duration of response, overall survival, and safety were the secondary endpoints. Analyses were in the modified intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02329080. The trial ended after accrual completion; the database lock was Dec 31, 2019.

Findings: Between March 30, 2015, and Aug 3, 2018, 79 patients were enrolled. 75 patients were assessable. 319 (71%) of the 450 planned courses were delivered. At 1 year from enrolment the primary endpoint was met, 42 patients were progression free (progression-free survival 58%; 95% CI 55-61). 49 patients (65%; 95% CI 54-76) had an objective response after MATRix-RICE, 29 (39%) of whom had a complete response. 37 patients who responded had autologous HSCT. At the end of the programme, 46 patients (61%; 95% CI 51-71) had an objective response, with a median duration of objective response of 26 months (IQR 16-37). At a median follow-up of 29 months (IQR 20-40), 35 patients were progression-free and 33 were alive, with a 2-year overall survival of 46% (95% CI 39-53). Grade 3-4 toxicity was most commonly haematological: neutropenia in 46 (61%) of 75 patients, thrombocytopenia in 45 (60%), and anaemia in 26 (35%). 79 serious adverse events were recorded in 42 (56%) patients; four (5%) of those 79 were lethal due to sepsis caused by Gram-negative bacteria (treatment-related mortality 5%; 95% CI 0·07-9·93).

Interpretation: MATRix-RICE plus autologous HSCT was active in this population of patients with very poor prognosis, and had an acceptable toxicity profile.

Funding: Stand Up To Cancer Campaign for Cancer Research UK, the Swiss Cancer Research foundation, and the Swiss Cancer League.
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http://dx.doi.org/10.1016/S2352-3026(20)30366-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844712PMC
February 2021

Allogeneic Stem Cell Transplantation in Mantle Cell Lymphoma in the Era of New Drugs and CAR-T Cell Therapy.

Cancers (Basel) 2021 Jan 14;13(2). Epub 2021 Jan 14.

SC Ematologia, Azienda Ospedaliera Santi Antonio e Biagio e Cesare Arrigo, 15121 Alessandria, Italy.

MCL is an uncommon lymphoproliferative disorder that has been regarded as incurable since its identification as a distinct entity. Allogeneic transplantation for two decades has represented the only option capable of ensuring prolonged remissions and possibly cure. Despite its efficacy, its application has been limited by feasibility limitations and substantial toxicity, particularly in elderly patients. Nevertheless, the experience accumulated over time has been wide though often scattered among retrospective and small prospective studies. In this review, we aimed at critically revise and discuss available evidence on allogeneic transplantation in MCL, trying to put available evidence into the 2020 perspective, characterized by unprecedented development of novel promising therapeutic agents and regimens.
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http://dx.doi.org/10.3390/cancers13020291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830938PMC
January 2021

Lenalidomide maintenance after autologous haematopoietic stem-cell transplantation in mantle cell lymphoma: results of a Fondazione Italiana Linfomi (FIL) multicentre, randomised, phase 3 trial.

Lancet Haematol 2021 Jan 22;8(1):e34-e44. Epub 2020 Dec 22.

Department of Translational and Precision Medicine, Sapienza University of Rome, Roma, Italy.

Background: Fit patients with mantle cell lymphoma aged 18-65 years are usually given cytarabine and rituximab-based induction regimens followed by autologous haematopoetic stem-cell transplantation (HSCT). We investigated whether post-autologous HSCT maintenance with lenalidomide improves progression-free survival in this population.

Methods: This open-label, randomised, multicentre, phase 3 trial was done at 49 haematology and oncology units in Italy and Portugal. Eligible patients had Ann Arbor stage III or IV treatment-naive mantle cell lymphoma (or stage II plus bulky disease [≥5 cm] or B symptoms), and had evidence of cyclin D1 overexpression or the translocation t(11;14)(q13;q32). Patients were aged 18-59 years with Eastern Cooperative Oncology Group (ECOG) performance status 0-3, or aged 60-65 years with ECOG 0-2. After an optional prephase with vincristine and steroids (intravenous vincristine 1·4 mg/m on day 1, oral prednisone 100 mg [total dose] on days 1-5), patients were given three courses of R-CHOP (21-day cycle, intravenous rituximab 375 mg/m on day 1; intravenous doxorubicin 50 mg/m, vincristine 1·4 mg/m, and cyclophosphamide 750 mg/m on day 2; oral prednisone 100 mg/m on day 2-6). Patients then received one cycle of high-dose CTX (intravenous cyclophosphamide 4 g/m on day 1, intravenous rituximab 375 mg/m on day 4). After restaging, patients received two cycles of R-HD-cytarabine (high-dose intravenous cytarabine 2 g/m every 12 h on days 1-3, intravenous rituximab 375 mg/m on days 4 and 10). Patients with complete remission or partial remission proceeded to autologous HSCT and responding patients (complete remission or partial remission) with haematological recovery were randomly assigned (1:1) to receive 24 courses of oral lenalidomide maintenance (15 mg per day for patients with platelets >100 × 10 cells per L or 10 mg per day for platelets 60-100 × 10 cells per L, days 1-21 every 28 days) for 24 months, or observation. The primary endpoint was progression-free survival, measured in the randomised population. This study is registered with EudraCT (2009-012807-25) and ClinicalTrials.gov (NCT02354313).

Findings: Between May 4, 2010, and Aug 24, 2015, 303 patients were screened for inclusion and 300 patients were enrolled (median age 57 years, IQR 51-62; 235 [78%] male). 95 patients were excluded before randomisation, mostly due to disease progression, adverse events, and inadequate recovery. 104 patients were randomly assigned to the lenalidomide maintenance group and 101 patients to the observation group. 11 (11%) of 104 patients assigned to lenalidomide did not start treatment (3 withdrew, 6 adverse events or protocol breach, 2 lost to follow-up). At a median follow-up of 38 months after randomisation (IQR 24-50), 3-year progression-free survival was 80% (95% CI 70-87) in the lenalidomide group versus 64% (53-73) in the observation group (log-rank test p=0·012; hazard ratio 0·51, 95% CI 0·30-0·87). 41 (39%) of 104 patients discontinued lenalidomide for reasons including death or progression. Treatment-related deaths were recorded in two (2%) of 93 patients in the lenalidomide group (1 pneumonia, 1 thrombotic thrombocytopenic purpura), and one (1%) of 101 in the observation group (pneumonia). 59 (63%) of 93 patients in the lenalidomide group had grade 3-4 haematological adverse events versus 12 (12%) of 101 patients in the observation group (p<0·0001). 29 (31%) of 93 patients in the lenalidomide group and eight (8%) of 101 patients in the observation group had grade 3-4 non-haematological adverse events (p<0·0001), of which infections were the most common.Serious adverse events were reported in 22 (24%) of 93 patients in the lenalidomide group and five (5%) of 101 patients in the observation group. Pneumonia and other infections were the most common serious adverse events.

Interpretation: Despite non-negligibile toxicity, lenalidomide after autologous HSCT improved progression-free survival in patients with mantle cell lymphoma, highlighting the role of maintenance in mantle cell lymphoma.

Funding: Fondazione Italiana Linfomi and Celgene.
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http://dx.doi.org/10.1016/S2352-3026(20)30358-6DOI Listing
January 2021

Phytotherapics in COVID19: Why palmitoylethanolamide?

Phytother Res 2020 Dec 9. Epub 2020 Dec 9.

Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.

At present, googling the search terms "COVID-19" and "Functional foods" yields nearly 500,000,000 hits, witnessing the growing interest of the scientific community and the general public in the role of nutrition and nutraceuticals during the COVID-19 pandemic. Many compounds have been proposed as phytotherapics in the prevention and/or treatment of COVID-19. The extensive interest of the general public and the enormous social media coverage on this topic urges the scientific community to address the question of whether which nutraceuticals can actually be employed in preventing and treating this newly described coronavirus-related disease. Recently, the Canadian biotech pharma company "FSD Pharma" received the green light from the Food and Drug Administration to design a proof-of-concept study evaluating the effects of ultramicronized palmitoylethanolamide (PEA) in COVID-19 patients. The story of PEA as a nutraceutical to prevent and treat infectious diseases dates back to the 1970s where the molecule was branded under the name Impulsin and was used for its immunomodulatory properties in influenza virus infection. The present paper aims at analyzing the potential of PEA as a nutraceutical and the previous evidence suggesting its anti-inflammatory and immunomodulatory properties in infectious and respiratory diseases and how these could translate to COVID-19 care.
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http://dx.doi.org/10.1002/ptr.6978DOI Listing
December 2020

A Study of the Radiation Tolerance of CVD Diamond to 70 MeV Protons, Fast Neutrons and 200 MeV Pions.

Authors:
Lukas Bäni Andreas Alexopoulos Marina Artuso Felix Bachmair Marcin Ryszard Bartosik Helge Christoph Beck Vincenzo Bellini Vladimir Belyaev Benjamin Bentele Alexandre Bes Jean-Marie Brom Gabriele Chiodini Dominik Chren Vladimir Cindro Gilles Claus Johann Collot John Cumalat Sébastien Curtoni Anne Evelyn Dabrowski Raffaello D'Alessandro Denis Dauvergne Wim De Boer Christian Dorfer Marc Dünser Gerald Eigen Vladimir Eremin Jacopo Forneris Laurent Gallin-Martel Marie-Laure Gallin-Martel Kock Kiam Gan Martin Gastal Abderrahman Ghimouz Mathieu Goffe Joel Goldstein Alexander Golubev Andrej Gorišek Eugene Grigoriev Jörn Grosse-Knetter Aidan Grummer Bojan Hiti Dmitry Hits Martin Hoeferkamp Jérôme Hosselet Fabian Hügging Chris Hutson Jens Janssen Harris Kagan Keida Kanxheri Richard Kass Mladen Kis Gregor Kramberger Sergey Kuleshov Ana Lacoste Stefano Lagomarsino Alessandro Lo Giudice Ivan López Paz Eric Lukosi Chaker Maazouzi Igor Mandić Sara Marcatili Alysia Marino Cédric Mathieu Mauro Menichelli Marko Mikuž Arianna Morozzi Francesco Moscatelli Joshua Moss Raymond Mountain Alexander Oh Paolo Olivero Daniele Passeri Heinz Pernegger Roberto Perrino Federico Picollo Michal Pomorski Renato Potenza Arnulf Quadt Fatah Rarbi Alessandro Re Michael Reichmann Shaun Roe Olivier Rossetto Diego Alejandro Sanz Becerra Christian J Schmidt Stephen Schnetzer Silvio Sciortino Andrea Scorzoni Sally Seidel Leonello Servoli Dale Shane Smith Bruno Sopko Vit Sopko Stefania Spagnolo Stefan Spanier Kevin Stenson Robert Stone Bjarne Stugu Concetta Sutera Michael Traeger William Trischuk Marco Truccato Cristina Tuvè Jaap Velthuis Stephen Wagner Rainer Wallny Jianchun Wang Norbert Wermes Jayashani Wickramasinghe Mahfoud Yamouni Justas Zalieckas Marko Zavrtanik Kazuhiko Hara Yoichi Ikegami Osamu Jinnouchi Takashi Kohriki Shingo Mitsui Ryo Nagai Susumu Terada Yoshinobu Unno

Sensors (Basel) 2020 Nov 20;20(22). Epub 2020 Nov 20.

KEK, High Energy Accelerator Research Organization, Tsukuba, Ibaraki 305-0801, Japan.

We measured the radiation tolerance of commercially available diamonds grown by the Chemical Vapor Deposition process by measuring the charge created by a 120 GeV hadron beam in a 50 μm pitch strip detector fabricated on each diamond sample before and after irradiation. We irradiated one group of samples with 70 MeV protons, a second group of samples with fast reactor neutrons (defined as energy greater than 0.1 MeV), and a third group of samples with 200 MeV pions, in steps, to (8.8±0.9) × 10 protons/cm, (1.43±0.14) × 10 neutrons/cm, and (6.5±1.4) × 10 pions/cm, respectively. By observing the charge induced due to the separation of electron-hole pairs created by the passage of the hadron beam through each sample, on an event-by-event basis, as a function of irradiation fluence, we conclude all datasets can be described by a first-order damage equation and independently calculate the damage constant for 70 MeV protons, fast reactor neutrons, and 200 MeV pions. We find the damage constant for diamond irradiated with 70 MeV protons to be 1.62±0.07(stat)±0.16(syst)× 10 cm/(p μm), the damage constant for diamond irradiated with fast reactor neutrons to be 2.65±0.13(stat)±0.18(syst)× 10 cm/(n μm), and the damage constant for diamond irradiated with 200 MeV pions to be 2.0±0.2(stat)±0.5(syst)× 10 cm/(π μm). The damage constants from this measurement were analyzed together with our previously published 24 GeV proton irradiation and 800 MeV proton irradiation damage constant data to derive the first comprehensive set of relative damage constants for Chemical Vapor Deposition diamond. We find 70 MeV protons are 2.60 ± 0.29 times more damaging than 24 GeV protons, fast reactor neutrons are 4.3 ± 0.4 times more damaging than 24 GeV protons, and 200 MeV pions are 3.2 ± 0.8 more damaging than 24 GeV protons. We also observe the measured data can be described by a universal damage curve for all proton, neutron, and pion irradiations we performed of Chemical Vapor Deposition diamond. Finally, we confirm the spatial uniformity of the collected charge increases with fluence for polycrystalline Chemical Vapor Deposition diamond, and this effect can also be described by a universal curve.
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http://dx.doi.org/10.3390/s20226648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699799PMC
November 2020

A dose-dense short-term therapy for human immunodeficiency virus/acquired immunodeficiency syndrome patients with high-risk Burkitt lymphoma or high-grade B-cell lymphoma: safety and efficacy results of the "CARMEN" phase II trial.

Br J Haematol 2021 01 21;192(1):119-128. Epub 2020 Oct 21.

Division of Hematology, Ospedali Civili di Brescia, Brescia, Italy.

A few prospective trials in HIV-positive patients with Burkitt lymphoma (BL) or high-grade B-cell lymphoma (HGBL) have been reported. Investigated therapies have shown good efficacy but relevant safety problems, with high rates of interruptions, severe mucositis, septic complications, and fungal infections. Here, we report the results of a multicentre phase II trial addressing a new dose-dense, short-term therapy aimed at maintaining efficacy and improving tolerability. The experimental programme included a 36-day polychemotherapy induction followed by high-dose cytarabine-based consolidation and response-tailored BEAM (carmustine, etoposide, cyatarabine, and melphalan)- conditioned autologous stem cell transplantation (ASCT). This therapy would be considered active if ≥11 complete remissions (CR) after induction (primary endpoint) were recorded among 20 assessable patients. HIV-positive adults (median age 42, range 26-58; 16 males) with untreated BL (n = 16), HGBL (n = 3) or double-hit lymphoma (n = 1) were enrolled. All patients had high-risk features, with meningeal and bone marrow infiltration in five and nine patients respectively. The experimental programme was safe and active in a multicentre setting, with only two episodes of grade 4 non-haematological toxicity (hepatotoxicity and mucositis), and no cases of systemic fungal infections; two patients died of toxicity (bacterial infections). Response after induction (median duration: 47 days; interquartile range 41-54), was complete in 13 patients and partial in five [overall response rate = 90%; 95% confidence interval (CI) = 77-100]. All responders received consolidation, and five required autologous stem cell transplant. At a median follow-up of 55 (41-89) months, 14 patients are relapse-free and 15 are alive, with a five-year progression-free survival and an overall survival of 70% (95% CI = 60-80%) and 75% (95% CI = 66-84) respectively. No patient with cerebrospinal fluid (CSF)/meningeal lymphoma experienced central nervous system recurrence. With respect to previously reported regimens, this programme was delivered in a shorter period, and achieved the main goal of maintaining efficacy and improving tolerability.
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http://dx.doi.org/10.1111/bjh.17188DOI Listing
January 2021

Lathyrus sativus diamine oxidase reduces Clostridium difficile toxin A-induced toxicity in Caco-2 cells by rescuing RhoA-GTPase and inhibiting pp38-MAPK/NF-κB/HIF-1α activation.

Phytother Res 2021 Jan 10;35(1):415-423. Epub 2020 Sep 10.

Department of Biochemical Sciences "A. Rossi Fanelli", Faculty of Pharmacy and Medicine, Sapienza University of Rome, Rome, Italy.

Clostridium difficile toxin A (TcdA) impairs the intestinal epithelial barrier, increasing the mucosa permeability and triggering a robust inflammatory response. Lathyrus sativus diamino oxidase (LSAO) is a nutraceutical compound successfully used in various gastrointestinal dysfunctions. Here, we evaluated the LSAO (0.004-0.4 μM) ability to counter TcdA-induced (30 ng/mL) toxicity and damage in Caco-2 cells, investigating its possible mechanism of action. LSAO has improved the transepithelial electrical resistance (TEER) score and increased cell viability in TcdA-treated cells, significantly rescuing the protein expression of Ras homolog family members, A-GTPase (RhoA-GTPase), occludin, and zonula occludens-1 (ZO-1). LSAO has also exhibited an anti-apoptotic effect by inhibiting the TcdA-induced expression of Bcl-2-associated X protein (Bax), p50 nuclear factor-kappa-B (p50), p65nuclear factor-kappa-B (p65), and hypoxia-inducible transcription factor-1 alpha (HIF-1α), and the release of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF) in the cell milieu. Our data showed that LSAO exerts a protective effect on TcdA-induced toxicity in Caco-2 cells, placing itself as an interesting nutraceutical to supplement the current treatment of the Clostridium difficile infections.
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http://dx.doi.org/10.1002/ptr.6814DOI Listing
January 2021

Clinical characteristics and risk factors for mortality in hematologic patients affected by COVID-19.

Cancer 2020 12 10;126(23):5069-5076. Epub 2020 Sep 10.

Hematology Department, ASST Spedali Civili, Brescia, Italy.

Background: Patients with cancer are considered highly vulnerable to the recent coronavirus disease 2019 (COVID-19) pandemic. However, there are still few data on COVID-19 occurring in hematologic patients.

Methods: One hundred two patients with COVID-19 symptoms and a nasopharyngeal swab positive for severe acute respiratory syndrome coronavirus 2 seen at 2 hematologic departments located in Lombardy, Italy, during March 2020 were studied. Risk factors for acquiring COVID-19 were analyzed by comparisons of patients with COVID-19 and the standard hematologic population managed at the same institutions in 2019. Thirty-day survival was compared with the survival of matched uninfected control patients with similar hematologic disorders and nonhematologic patients affected by COVID-19.

Results: Male sex was significantly more prevalent in patients with COVID-19. The infection occurred across all different types of hematologic disease; however, the risk of acquiring a COVID-19 infection was lower for patients with chronic myeloproliferative neoplasms, including chronic myeloid leukemia, and higher for patients with immune-mediated anemia on immunosuppressive-related treatments. The 30-day mortality rate was 39.2%, which was higher than the rates for nonhematologic patients with COVID-19 (23.5%; P = .02) and uninfected hematologic controls (3%; P < .001). The severity of the respiratory syndrome at presentation and active hematologic treatment were independently associated with a worse prognosis. Neither diagnosis nor disease status affected the prognosis. The worst prognosis was demonstrated among patients on active hematologic treatment and those with more severe respiratory syndrome at COVID-19 presentation.

Conclusions: During the COVID-19 pandemic, patients should be advised to seek medical attention at the earliest signs of dyspnea and/or respiratory infection. Physicians should perform a risk-benefit analysis to determine the impact of temporarily deferring nonlifesaving treatments versus the risk of adverse outcomes associated with COVID-19.

Lay Summary: Coronavirus disease 2019 (COVID-19) infection occurs across all different types of hematologic disease; however, the risk of acquiring it is lower for patients with chronic myeloproliferative neoplasms, including chronic myeloid leukemia, and higher for patients with immune-mediated anemia on immunosuppressive treatment. The 30-day mortality rate is 39.2%, which is far higher than the rates for both uninfected hematologic controls (3%; P < .001) and nonhematologic patients with COVID-19 (23.5%; P = .02) despite matching for age, sex, comorbidities, and severity of disease. Variables independently associated with a worse prognosis are the severity of the respiratory syndrome at presentation and any type of active hematologic treatment. Neither diagnosis nor disease status influence the prognosis.
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http://dx.doi.org/10.1002/cncr.33160DOI Listing
December 2020

Treatment management of haematological malignancies in people living with HIV.

Lancet Haematol 2020 Sep 10;7(9):e679-e689. Epub 2020 Aug 10.

Department of Haemato-Oncology, St Bartholomew's Hospital, London, UK.

Although the incidence of HIV-associated lymphomas decreased after the introduction of effective combination antiretroviral therapy, they became the most common AIDS-related cancer in high-income countries. Moreover, as people living with HIV live longer, a wide range of non-AIDS-related cancer has emerged, including other haematological malignancies. Nonetheless, combination antiretroviral therapy has offered people with HIV the opportunity to receive the same therapies as those provided to the general population, and intensive curative therapies have become the standard. However, several population-based studies highlight a major health-care disparity between people with HIV and those without, with people who are HIV positive often excluded from using innovative therapies and participating in prospective trials. In addition, patients from low-income countries frequently receive inappropriate treatment. The hope is that with increased awareness of effective curative options these disparities will decrease, and people with HIV will be given the same therapeutic opportunities and enrolled in clinical trials alongside patients who are HIV negative.
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http://dx.doi.org/10.1016/S2352-3026(20)30115-0DOI Listing
September 2020

Assessment in the Supine-To-Stand Task and Functional Health from Youth to Old Age: A Systematic Review.

Int J Environ Res Public Health 2020 08 10;17(16). Epub 2020 Aug 10.

Department of Physical Education, College of Education, University of South Carolina, Columbia, SC 29208, USA.

Performance in the supine-to-stand (STS) task is an important functional and health marker throughout life, but the evaluation methods and some correlates can impact it. This article aims to examine the studies that assessed the performance of the STS task of young people, adults and the elderly. Evidence of the association between the STS task and body weight status, musculoskeletal fitness and physical activity was investigated, and a general protocol was proposed. MEDLINE/Pubmed and Web of Science databases were accessed for searching studies measuring the STS task directly; identification, objective, design, sample, protocols and results data were extracted; the risk of bias was assessed (PROSPERO CRD42017055693). From 13,155 studies, 37 were included, and all demonstrated a low to moderate risk of bias. The STS task was applied in all world, but the protocols varied across studies, and they lacked detail; robust evidence demonstrating the association between STS task and musculoskeletal fitness was found; there was limited research examining body weight status, physical activity and the STS task performance. In conclusion, the STS task seems to be a universal tool to track motor functional competence and musculoskeletal fitness throughout life for clinical or research purposes.
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http://dx.doi.org/10.3390/ijerph17165794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460168PMC
August 2020

Outcomes in first relapsed-refractory younger patients with mantle cell lymphoma: results from the MANTLE-FIRST study.

Leukemia 2021 03 11;35(3):787-795. Epub 2020 Aug 11.

Unit of Hematology, Humanitas Clinical and Research Center, Milan, Italy.

Patients with mantle cell lymphoma (MCL) that fail induction treatment represent a difficult-to-treat population, where no standard therapy exists. We evaluated outcomes in patients with first relapsed-refractory (r/r) MCL after upfront high dose cytarabine including standard regimens. Overall survival (OS-2) and progression-free survival (PFS-2) were estimated from the time of salvage therapy. The previously described threshold of 24 months was used to define patients as early- or late-progressors (POD). Overall, 261 r/r MCL patients were included. Second-line regimens consisted of rituximab-bendamustine (R-B, 21%), R-B and cytarabine (R-BAC, 29%), ibrutinib (19%), and others (31%). The four groups were balanced in terms of clinicopathological features. Adjusting for age and early/late-POD, patients treated with R-BAC had significantly higher complete remission (63%) than comparators. Overall, Ibrutinib and R-BAC were associated with improved median PFS-2 [24 and 25 months, respectively], compared to R-B (13) or others (7). In patients with early-POD (n = 127), ibrutinib was associated with inferior risk of death than comparators (HR 2.41 for R-B, 2.17 for others, 2.78 for R-BAC). In patients with late-POD (n = 134), no significant differences were observed between ibrutinib and bendamustine-based treatments. Ibrutinib was associated with improved outcome in early-POD patients.
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http://dx.doi.org/10.1038/s41375-020-01013-3DOI Listing
March 2021

Clinical and prognostic role of interim 18F-FDG PET/CT in elderly Hodgkin lymphoma: a dual-center experience.

Leuk Lymphoma 2020 12 24;61(13):3209-3216. Epub 2020 Jul 24.

Nuclear Medicine, University of Brescia and Spedali Civili Brescia, Brescia, Italy.

Hodgkin lymphoma (HL) has a bimodal age distribution curve, with a second peak in people aged more than 60 years. Interim PET/CT (iPET/CT) is highly predictive for PFS and OS in young HL, but it has not been sufficiently studied in the elderly. In this retrospective dual-center study, 82 patients with HL and aged 65 or more who performed iPET/CT were included. At iPET/CT, 60 patients had a complete metabolic response, 18 partial responses, and 4 progressions of disease. Baseline PET/CT metabolic features were not significantly correlated with the metabolic response at interim. In patients with interim complete metabolic response, PFS and OS were significantly longer than in patients without complete response( < 0.001 and  = 0.004). Patients with negative iPET had 2-year PFS and OS rates of 57 and 88% compared with 24 and 58% in patients with positive iPET ( < 0.001). iPET/CT results demonstrated to be independent prognostic factors for PFS and OS.
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http://dx.doi.org/10.1080/10428194.2020.1797012DOI Listing
December 2020

Treatment of very high-risk classical Hodgkin Lymphoma: cases' selection from real life and critical review of the literature.

Acta Biomed 2020 05 25;91(S-5):13-22. Epub 2020 May 25.

Hematology Unit, Antonio e Biagio e Cesare Arrigo Hospital, Alessandria, Italy.

Over the last 4 decades, advances in radiation therapy and the addition of combination chemotherapy have significantly increased the cure rate of patients with HL, with a 5-year OS of about 90% . However, despite high rate of cure after first line of therapy, 5%-10% of HLs are refractory to the treatment, and 10-30% of patients have a disease relapse after a complete response (CR). Relapsed HL can be treated with salvage therapies with a long-lasting complete remission in 80% of cases. In recent years, novel drugs are available for the patients with relapsed/refractory HL, like Brentuximab Vedotin and immune checkpoint inhibitors. These drugs have been able to rescue a cohort of patients who subsequently could receive an allogeneic stem-cell transplant. Our cases have been chosen because they are representative of critical issues in the management of relapsed/refractory HL; our experiences are consistent with what reported by other Authors.
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http://dx.doi.org/10.23750/abm.v91iS-5.9911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944652PMC
May 2020

Long-lasting efficacy and safety of lenalidomide maintenance in patients with relapsed diffuse large B-cell lymphoma who are not eligible for or failed autologous transplantation.

Hematol Oncol 2020 Aug 5;38(3):257-265. Epub 2020 May 5.

Vita-Salute San Raffaele University, Milan, Italy.

We report final results of a phase II trial addressing efficacy and feasibility of lenalidomide maintenance in patients with chemosensitive relapse of diffuse large B-cell lymphoma (DLBCL) not eligible for or failed after autologous stem cell transplantation (ASCT). Patients with relapsed DLBCL who achieved at least a partial response to salvage chemoimmunotherapy were enrolled and treated with lenalidomide 25 mg/day for 21 of 28 days for 2 years or until progression or unacceptable toxicity. Primary endpoint was 1-year PFS. Forty-six of 48 enrolled patients were assessable. Most patients had IPI ≥2, advanced stage and extranodal disease before the salvage treatment that led to trial registration; 28 (61%) patients were older than 70 years. Lenalidomide was well tolerated. With the exception of neutropenia, grade-4 toxicities occurred in <1% of courses. Three patients died of complications during maintenance and three died due to second cancers at 32 to 64 months. There were 13 SAEs recorded in 12 patients; all these patients but two recovered. Lenalidomide was interrupted due to toxicity in other 6 patients, and 25 patients required dose reduction (transient in 21). At 1 year from registration, 31 patients were progression free. After a median follow-up of 65 (range 39-124) months, 22 patients remain progression free, with a 5-year PFS of 48% ± 7%. The duration of response to lenalidomide was longer than response to prior treatment in 30 (65%) patients. Benefit was observed both in de novo and transformed DLBCL, germinal-center-B-cell and nongerminal-center-B-cell subtypes. Twenty-six patients are alive (5-year OS 62% ± 7%). With the limitations of a nonrandomized design, these long-term results suggest that lenalidomide maintenance might bring benefit to patients with chemosensitive relapse of DLBCL not eligible for or failed after ASCT. Lenalidomide was associated with durable disease control and was well tolerated in this elderly population. Further investigations on immunomodulatory drugs as maintenance in these high-risk patients are warranted.
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http://dx.doi.org/10.1002/hon.2742DOI Listing
August 2020

Five-year results of the BEGEV salvage regimen in relapsed/refractory classical Hodgkin lymphoma.

Blood Adv 2020 01;4(1):136-140

Department of Hematology and Oncology, Humanitas Cancer Center, Humanitas Clinical and Research Center, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rozzano, Milan, Italy.

The complete remission (CR) rate achieved with induction chemotherapy prior to autologous stem cell transplantation (ASCT) represents the strongest prognostic factor in relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL). By inducing a CR rate of 75%, the bendamustine, gemcitabine, vinorelbine (BEGEV) regimen represents an optimal chemotherapy regimen prior to ASCT. Presented here are the 5-year results of BEGEV followed by ASCT in R/R cHL. With a median follow-up of 5 years, progression-free survival (PFS) and overall survival (OS) for the whole series (n = 59) were 59% and 78%, respectively. ASCT was performed in 43 of 49 responding patients (73% by intention to treat [ITT]; 88% by response to BEGEV) and resulted in 33 with continuous CR (56% by ITT; 77% of transplanted patients), 7 with disease relapse, and 3 with nonrelapse mortality. For patients who received transplants, the 5-year PFS and OS were 77% and 91%, respectively, with no significant difference between relapsed and refractory patients. No patient experienced secondary leukemia or myelodysplasia. In summary, the long-term efficacy data, the benefits for both relapsed and refractory patients, and the excellent safety profile provide a strong rationale for further development of the BEGEV regimen. This trial was registered at EudraCT as #2010-022169-91 and at www.clinicaltrials.gov as #NCT01884441.
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http://dx.doi.org/10.1182/bloodadvances.2019000984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6960479PMC
January 2020

The classic prognostic factors in advanced Hodgkin's lymphoma patients are losing their meaning at the time of Pet-guided treatments.

Ann Hematol 2020 Feb 23;99(2):277-282. Epub 2019 Dec 23.

Policlinico S.Orsola-Malpighi, Istituto di Ematologia "Seragnoli", Bologna, Italy.

The International Prognostic Score (IPS) is the most commonly used risk stratification tool for patients with advanced Hodgkin lymphoma (HL). It incorporates seven clinical parameters independently associated with a poorer outcome: male sex, age, stage IV, hemoglobin level, white blood cell and lymphocyte counts, and albumin level. Since the development of the IPS, there have been significant advances in therapy and supportive care. Recent studies suggest that the IPS is less discriminating due to improved outcomes with ABVD therapy. The aim of the present study was to asses if classic prognostic factors maintain their prognostic meaning at the time of response-adapted treatment based on interim PET scans. We evaluated the prognostic significance of IPS in the 520 advanced stage HL patients enrolled in the PET-guided, HD0801 trial in which PET2-positive patients underwent a more intense treatment with an early stem-cell transplantation after 2 cycles of ABVD. We observed that in these patients, the IPS completely loses its prognostic value together with all the single parameters that contribute to the IPS. Furthermore, neutrophils, monocytes, lymphocytes, and the ratio among them also no longer had any predictive value. We believe that the substantial improvement in survival outcomes in PET2-positive patients treated with early autologous transplantation could explain the complete disappearance of the residual prognostic significance of the IPS.
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http://dx.doi.org/10.1007/s00277-019-03893-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976582PMC
February 2020

Clinical characteristics of interim-PET negative patients with a positive end PET from the prospective HD08-01 FIL study.

Ann Hematol 2020 Feb 23;99(2):283-291. Epub 2019 Dec 23.

Institute of Hematology "L. e A. Seràgnoli", University of Bologna, Bologna, Italy.

FDG-positron emission tomography (PET) performed early during therapy in advanced Hodgkin lymphoma patients has been confirmed as being important for progression-free survival. A group of patients with a negative interim-PET (i-PET) showed a positive end induction PET (e-PET). The aim of this study was to evaluate the clinical characteristics of patients with a positive e-PET as a secondary end point of the HD0801 study. A total of 519 patients with advanced-stage de novo Hodgkin lymphoma received initial treatment and underwent an i-PET. Patients with negative results continued the standard treatment. i-PET negative patients were then evaluated for response with an e-PET and those patients found to have a positive one were also then given a salvage therapy. Among 409 i-PET negative, 16 interrupted the therapy, 393 patients were evaluated with an e-PET, and 39 were positive. Sixteen out of 39 underwent a diagnostic biopsy and 15 were confirmed as HD. Seventeen out of 39 e-PET were reviewed according to the Deauville Score and, in sixteen, it was confirmed positive (10 DS 5, 6 DS 4). With the exception of high LDH value at diagnosis (p = 0.01; HR 95% CI 1.18-4.89), no clinical characteristics were significantly different in comparison with e-PET negative patients. Positive e-PET after a negative i-PET has a worse outcome when compared with i-PET positive patients salvaged with therapy intensification. It was not possible to identify clinical characteristics associated with a positive e-PET.
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http://dx.doi.org/10.1007/s00277-019-03889-3DOI Listing
February 2020

Is motor competence associated with the risk of central obesity in preschoolers?

Am J Hum Biol 2020 05 26;32(3):e23364. Epub 2019 Nov 26.

Department of Physical Education, Federal University of Pernambuco, Recife, Brazil.

Objectives: To investigate the association between motor competence (MC) and central obesity in preschool children.

Methods: The sample comprised of 472 children aged 3 to 5 years (4.58 ± 0.70 years, 248 boys) from Recife, Brazil. MC was assessed using the Test of Gross Motor Development-2. Waist-to-height ratio (WHtR) was calculated and a cutoff of 0.5 was used to define central obesity. Logistic regression was used to examine the association between MC and WHtR ≥ 0.5.

Results: The prevalence of central obesity (WHtR) was 54.0% and 46.4% for boys and girls, respectively. Older children (OR = 0.61; CI = 0.44-0.84; P < .01) and those with higher MC in locomotor skills (OR = 0.96; CI = 0.93-0.99; P < .01) were less likely to present WHtR ≥ 0.5. Sex and object control skills were not associated with WHtR ≥ 0.5.

Conclusions: To reduce the risks of central obesity in children, health practitioners should focus on increasing competence in locomotor skills since preschool years.
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http://dx.doi.org/10.1002/ajhb.23364DOI Listing
May 2020

Motor learning and transfer between real and virtual environments in young people with autism spectrum disorder: A prospective randomized cross over controlled trial.

Autism Res 2020 02 30;13(2):307-319. Epub 2019 Sep 30.

School of Arts, Sciences and Humanities, University of São Paulo, São Paulo, SP, Brazil.

Autism spectrum disorder (ASD) is associated with persistent deficits in social communication and social interaction, including impaired multisensory integration, which might negatively impact cognitive and motor skill performance, and hence negatively affect learning of tasks. Considering that tasks in virtual environment may provide an engaging tool as adjuncts to conventional therapies, we set out to compare motor performance between young people with ASD and a typically developing (TD) control group that underwent coincident timing tasks based on Kinect (no physical contact) and on Keyboard (with physical contact) environments. Using a randomized repeated cross-over controlled trial design, 50 young people with ASD and 50 with TD, matched by age and sex were divided into subgroups of 25 people that performed the two first phases of the study (acquisition and retention) on the same device-real or virtual-and then switched to the other device to repeat acquisition and retention phases and finally switched on to a touch screen (transfer phase). Results showed that practice in the virtual task was more difficult (producing more errors), but led to a better performance in the subsequent practice in the real task, with more pronounced improvement in the ASD as compared to the TD group. It can be concluded that the ASD group managed to transfer the practice from a virtual to a real environment, indicating that virtual methods may enhance learning of motor and cognitive skills. A need for further exploration of its effect across a number of tasks and activities is warranted. Autism Res 2020, 13: 307-319. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Individuals with autism spectrum disorder are known to have difficulties with learning motor tasks. Considering that performing motor tasks in virtual environment may be an engaging tool as adjuncts to conventional therapies, we aimed to estimate performance in tasks regardless of physical touch. Results showed that participants had more difficulty using the non-touch task; however, virtual training improved performance on the physical (real) task. This result indicates that virtual methods could be a promising therapeutic approach for the ASD population.
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http://dx.doi.org/10.1002/aur.2208DOI Listing
February 2020

An increase in copy number has a progressive negative prognostic impact in patients with diffuse large B-cell and high-grade lymphoma, who may benefit from intensified treatment regimens.

Haematologica 2020 05 8;105(5):1369-1378. Epub 2019 Aug 8.

Department of Hematology, ASST Spedali Civili di Brescia.

translocations, a hallmark of Burkitt lymphoma, occur in 5-15% of diffuse large B-cell lymphoma, and have a negative prognostic impact. Numerical aberrations of have also been detected in these patients, but their incidence and prognostic role are still controversial. We analyzed the clinical impact of increased copy number on 385 patients with diffuse large B-cell lymphoma screened at diagnosis for , , and rearrangements. We enumerated the number of copies, defining as amplified those cases with an uncountable number of extra-copies. The prevalence of translocation, increased copy number and amplification was 8.8%, 15%, and 1%, respectively. Patients with 3 or 4 gene copies, accounting for more than 60% of patients with copy number changes, had a more favorable outcome compared to patients with >4 copies or translocation of MYC, and were not influenced by the type of treatment received as first-line. Stratification according to the number of extra-copies showed a negative correlation between an increasing number of copies and survival. Patients with >7 copies or the amplification of had the poorest prognosis. Patients with >4 copies of MYC showed a similar, trending towards worse prognosis compared to patients with translocation. The survival of patients with >4 copies, translocation or amplification of seemed to be superior if intensive treatments were used. Our study underlines the importance of fluorescence hybridization testing at diagnosis of diffuse large B-cell lymphoma to detect the rather frequent and clinically significant numerical aberrations of .
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http://dx.doi.org/10.3324/haematol.2019.223891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193495PMC
May 2020

Bleomycin, vinblastine and dacarbazine combined with nonpegylated liposomal doxorubicin (MBVD) in elderly (≥70 years) or cardiopathic patients with Hodgkin lymphoma: a phase-II study from Fondazione Italiana Linfomi (FIL).

Leuk Lymphoma 2019 12 8;60(12):2890-2898. Epub 2019 Jul 8.

Hematology Unit, Azienda Unità Sanitaria Locale IRCCS, Reggio Emilia, Italy.

This phase-II study assessed activity and toxicity of substituting conventional doxorubicin with nonpegylated liposomal doxorubicin in the conventional ABVD regimen for the treatment of elderly or cardiopathic patients with HL. Stage I-IIA and IIB-IV patients were treated with three courses of MBVD plus radiotherapy, or six courses of MBVD, respectively, plus radiotherapy limited to bulky or residual disease areas. The primary endpoints were CR rate and the rate of cardiac events. Forty-seven patients were enrolled. Median age was 75 years, 13 had stage I-II disease. Overall, CR was achieved by 36 patients (77%, 95% CI: 62-88), 100% and 68% in stage I-II and III-IV, respectively. With a median follow-up of 40 months (IQR: 36-45). Three-year overall survival (OS) and progression-free survival (PFS) were 70% and 43%, respectively. Cardiac events grades 3-5 were reported in two patients. In conclusion, MBVD's activity and safety profile was comparable to historical ABVD data.
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http://dx.doi.org/10.1080/10428194.2019.1608529DOI Listing
December 2019

Diagnostic and Clinical Impact of Staging F-FDG PET/CT in Mantle-Cell Lymphoma: A Two-Center Experience.

Clin Lymphoma Myeloma Leuk 2019 08 3;19(8):e457-e464. Epub 2019 May 3.

Nuclear Medicine, University of Brescia and Spedali Civili Brescia, Brescia, Italy.

Introduction: The diagnostic accuracy of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) in staging mantle-cell lymphoma has not yet investigated. The aim of this 2-center retrospective study was to investigate the utility of F-FDG PET/CT in assessing nodal, splenic, bone marrow (BM), and gastrointestinal (GI) disease compared to CT, BM, and GI endoscopy; and to assess its clinical impact.

Patients And Methods: One hundred twenty-two patients with histologically proven mantle-cell lymphoma were included. PET/CT BM findings were considered positive if isolated/multiple focal uptake in the BM not explained by benign findings and/or diffuse BM uptake higher than liver with/without focal uptakes were present. PET/CT findings were considered positive for GI involvement in the presence of isolated/multiple focal uptake in the GI organ.

Results: All patients had positive PET/CT showing the presence of at least one hypermetabolic lesion, with the exception of one case. PET/CT results, compared to CT, detected more nodal and/or splenic lesions in 26 patients. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET/CT for BM were 52%, 98%, 97%, 65%, and 74%; for GI 64%, 91%, 69%, 90%, and 85%; and for GI excluding diabetic patients, 78%, 92%, 72%, 94%, and 89%. PET/CT permitted upstaging of 21 cases and downstaging of 2.

Conclusion: F-FDG PET/CT showed excellent detection rate in nodal and splenic disease-a rate better than CT. For BM and GI evaluation, in order to reach good accuracy, the selection of patients and the use of specific criteria for evaluation of these organs seems to be crucial. Moreover, PET/CT altered the management and therapeutic approach in about 20% of patients.
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http://dx.doi.org/10.1016/j.clml.2019.04.016DOI Listing
August 2019

Invasive pulmonary aspergillosis in acute leukemia: a still frequent condition with a negative impact on the overall treatment outcome.

Leuk Lymphoma 2019 12 23;60(12):3044-3050. Epub 2019 May 23.

Hematology, ASST-Spedali Civili, Brescia, Italy.

We evaluated the impact of invasive pulmonary aspergillosis (IPA) on epidemiology and outcome in acute leukemia (AL), analyzing all acute myeloid (AML) and acute lymphoblastic leukemia (ALL) consecutively admitted to our Institution during a 5-year period of observation. Only AML patients received anti-mold prophylaxis. Among 175 AL patients (136 AML/39 ALL), possible and proven/probable IPA were diagnosed in 28 (16%). Frequency of IPA was similar in AML (16.2%) and in ALL (15.4%). Two-year overall survival (OS) was significantly affected by IPA (no IPA: 69.8% vs IPA: 31.7%  = .002). OS was similar in patients with proven/probable (28.2%) and possible IPA (36.4%) ( = .003 and .065, respectively). When censoring patients at transplant, IPA still affected 2-year survival (49.6% vs 79.2%,  = .02), but only proven/probable IPA was associated with lower survival (34.7%,  = .0003). IPA negatively impacts on long-term survival of leukemia patients; antifungal prophylaxis should be adopted also during induction in ALL and in AML beyond induction therapy.
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http://dx.doi.org/10.1080/10428194.2019.1613535DOI Listing
December 2019

Prognostic role of baseline 18F-FDG PET/CT metabolic parameters in mantle cell lymphoma.

Ann Nucl Med 2019 Jul 30;33(7):449-458. Epub 2019 Mar 30.

Nuclear Medicine, University of Brescia and Spedali Civili Brescia, P.le Spedali Civili 1, 25123, Brescia, Italy.

Objective: Mantle cell lymphoma (MCL) is an aggressive lymphoma sub-type with poor prognosis and high 18F-FDG avidity at PET/CT; nowadays, no validated criteria for PET/CT in treatment response evaluation and prediction of outcome are present. The aim of study was to investigate whether the metabolic PET/CT features may predict treatment evaluation and prognosis in MCL.

Methods: We retrospectively enrolled 87 patients who underwent baseline 18F-FDG PET/CT and 85 end-of-treatment (eot) PET/CT. The baseline PET images were analyzed visually and semi-quantitatively by measuring the maximum standardized uptake value body weight (SUVbw), lean body mass (SUVlbm), body surface area (SUVbsa), lesion-to-liver SUVmax ratio (L-L SUV R), lesion-to-blood pool SUVmax ratio (L-BP SUV R), metabolic tumor volume (MTV) and total lesion glycolysis (TLG). EotPET/CT was visually interpreted according to the criteria of the Deauville 5-point scale (DC). Survival curves were plotted according to the Kaplan-Meier method.

Results: At a median follow-up of 40 months, relapse/progression occurred in 47 and death in 23 patients. Median PFS and OS were 30 and 41 months. Baseline MTV and TLG were significantly higher in patients with progressive metabolic response compared to complete/partial response group. EotPET/CT results using DC significantly correlated with PFS, not with OS. MTV and TLG were demonstrated to be independent prognostic factors for PFS; instead the other metabolic parameters were not related to outcome survival. Considering OS, no variable was significantly associated.

Conclusions: EotPET/CT results (using DC), MTV and TLG were significantly correlated with response to treatment and PFS.
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http://dx.doi.org/10.1007/s12149-019-01354-9DOI Listing
July 2019

Autologous stem cell transplantation for HIV-associated lymphoma in the antiretroviral and rituximab era: a retrospective study by the EBMT Lymphoma Working Party.

Bone Marrow Transplant 2019 10 25;54(10):1625-1631. Epub 2019 Feb 25.

University Hospital of Heidelberg, Heidelberg, Germany.

The present study aimed at describing the outcome of patients with HIV-associated lymphomas following autologous hematopoietic stem cell transplantation (autoHCT) in the rituximab and combined antiretroviral therapy (cART) era. Eligible for this retrospective study were HIV-positive patients with lymphoma who received autoHCT between 2007 and 2013. A total of 118 patients were included with a median age of 45 years (range 24-66). Underlying diagnoses were diffuse large B cell lymphoma in 47%, Hodgkin lymphoma in 24%, Burkitt lymphoma in 18%, and plasmablastic lymphoma in 7% of patients. Disease status at autoHCT was complete remission in 44%, partial remission (PR) in 38%, and less than PR in 18% of the patients. With a median follow-up of 4 years, 3-year non-relapse mortality, incidence of relapse, progression-free survival (PFS) and overall survival (OS) were 10%, 27%, 63% and 66%, respectively. By multivariate analysis, disease status less than PR but not CD4+ cell count at the time of autoHCT was a significant predictor of unfavorable PFS and OS. In conclusion, in the era of cART and chemoimmunotherapy, the outcome of autoHCT for HIV-related lymphoma is driven by lymphoma-dependent risk factors rather than by characteristics of the HIV infection.
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http://dx.doi.org/10.1038/s41409-019-0480-xDOI Listing
October 2019