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1. Immune‐monitoring of myelodysplastic neoplasms: Recommendations from the i4MDS consortium

Author

Cristina A. Tentori, Lin P. Zhao, Benedetta Tinterri, Kathryn E. Strange, Katharina Zoldan, Konstantinos Dimopoulos, Xingmin Feng, Elena Riva, Benjamin Lim, Yannick Simoni, Vidhya Murthy, Madeline J. Hayes, Antonella Poloni, Eric Padron, Bruno A. Cardoso, Michael Cross, Susann Winter, Aida Santaolalla, Bhavisha A. Patel, Emma M. Groarke, Daniel H. Wiseman, Katy Jones, Lauren Jamieson, Charles Manogaran, Naval Daver, Laura Gallur, Wendy Ingram, P. Brent Ferrell, Katja Sockel, Nicolas Dulphy, Nicolas Chapuis, Anne S. Kubasch, Astrid M. Olsnes, Austin Kulasekararaj, Hugues De Lavellade, Wolfgang Kern, Mieke Van Hemelrijck, Dominique Bonnet, Theresia M. Westers, Sylvie Freeman, Uta Oelschlaegel, David Valcarcel, Marco G. Raddi, Kirsten Grønbæk, Michaela Fontenay, Sanam Loghavi, Valeria Santini, Antonio M. Almeida, Jonathan M. Irish, David A. Sallman, Neal S. Young, Arjan A. van deLoosdrecht, Lionel Adès, Matteo G. Della Porta, Catherine Cargo, Uwe Platzbecker, Shahram Kordasti, and i4MDS consortium

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Abstract Advancements in comprehending myelodysplastic neoplasms (MDS) have unfolded significantly in recent years, elucidating a myriad of cellular and molecular underpinnings integral to disease progression. While molecular inclusions into prognostic models have substantively advanced risk stratification, recent revelations have emphasized the pivotal role of immune dysregulation within the bone marrow milieu during MDS evolution. Nonetheless, immunotherapy for MDS has not experienced breakthroughs seen in other malignancies, partly attributable to the absence of an immune classification that could stratify patients toward optimally targeted immunotherapeutic approaches. A pivotal obstacle to establishing “immune classes” among MDS patients is the absence of validated accepted immune panels suitable for routine application in clinical laboratories. In response, we formed International Integrative Innovative Immunology for MDS (i4MDS), a consortium of multidisciplinary experts, and created the following recommendations for standardized methodologies to monitor immune responses in MDS. A central goal of i4MDS is the development of an immune score that could be incorporated into current clinical risk stratification models. This position paper first consolidates current knowledge on MDS immunology. Subsequently, in collaboration with clinical and laboratory specialists, we introduce flow cytometry panels and cytokine assays, meticulously devised for clinical laboratories, aiming to monitor the immune status of MDS patients, evaluating both immune fitness and identifying potential immune “risk factors.” By amalgamating this immunological characterization data and molecular data, we aim to enhance patient stratification, identify predictive markers for treatment responsiveness, and accelerate the development of systems immunology tools and innovative immunotherapies.

Published
2024
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2. Incidence of blast phase in myelofibrosis according to anemia severity

Author

Barbara Mora, Margherita Maffioli, Elisa Rumi, Paola Guglielmelli, Marianna Caramella, Andrew Kuykendall, Francesca Palandri, Alessandra Iurlo, Valerio De Stefano, Jean‐Jacques Kiladjian, Elena M. Elli, Nicola Polverelli, Jason Gotlib, Francesco Albano, Richard T. Silver, Giulia Benevolo, David M. Ross, Timothy Devos, Oscar Borsani, Tiziano Barbui, Matteo G. Della Porta, Lorenza Bertù, Rami Komrokji, Alessandro M. Vannucchi, and Francesco Passamonti

Subjects
acute myeloid leukemia, essential thrombocythemia, myelofibrosis, polycythemia vera, ruxolitinib, Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Abstract Myelofibrosis (MF) is a clonal malignancy frequently characterized by anemia and in 10%–20% of cases it can evolve into blast phase (BP). Anemia in MF is associated with reduced survival and ‐in primary MF‐ also with an increased probability of BP. Conventional treatments for anemia have limited effectiveness in MF. Within a dataset of 1752 MF subjects largely unexposed to ruxolitinib (RUX), BP incidence was 2.5% patients per year (p‐y). This rate reached respectively 4.3% and 4.5% p‐y in case of patients with common terminology criteria for adverse events (CTCAE) grade 3/4 and grade 2 anemia, respectively, that represented together 32% of the cohort. Among 273 MF cases treated with RUX, BP incidence was 2.89% p‐y and it reached 4.86% p‐y in subjects who started RUX with CTCAE grade 2 anemia (one third of total). Within patients with red blood cell transfusion‐dependency at 6 months of RUX (21% of the exposed), BP rate was 4.2% p‐y. Our study highlights a relevant incidence of BP in anemic MF patients, with a similar rate whether treated with or without RUX. These findings will help treating physicians to make decisions on the safety profile of innovative anemia treatments.

Published
2023
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3. Mild anemia and 11- to 15-year mortality risk in young-old and old-old: Results from two population-based cohort studies

Author

Alessia A. Galbussera, Sara Mandelli, Stefano Rosso, Roberto Zanetti, Marianna Rossi, Adriano Giacomin, Paolo Detoma, Emma Riva, Mauro Tettamanti, Matteo G. Della Porta, and Ugo Lucca

Subjects
Medicine, Science
Abstract

Background Mild anemia is a frequent although often overlooked finding in old age. Nevertheless, in recent years anemia has been linked to several adverse outcomes in the elderly population. Objective of the study was to investigate the association of mild anemia (hemoglobin concentrations: 10.0–11.9/12.9 g/dL in women/men) with all-cause mortality over 11–15 years and the effect of change in anemia status on mortality in young-old (65–84 years) and old-old (80+ years). Methods The Health and Anemia and Monzino 80-plus are two door-to-door, prospective population-based studies that included residents aged 65-plus years in Biella municipality and 80-plus years in Varese province, Italy. No exclusion criteria were used. Results Among 4,494 young-old and 1,842 old-old, mortality risk over 15/11 years was significantly higher in individuals with mild anemia compared with those without (young-old: fully-adjusted HR: 1.35, 95%CI, 1.15–1.58; old-old: fully-adjusted HR: 1.28, 95%CI, 1.14–1.44). Results were similar in the disease-free subpopulation (age, sex, education, smoking history, and alcohol consumption adjusted HR: 1.54, 95%CI, 1.02–2.34). Both age groups showed a dose-response relationship between anemia severity and mortality (P for trend Conclusions Findings from these two large prospective population-based studies consistently suggest an independent, long-term impact of mild anemia on survival at older ages.

Published
2021

4. SARS-CoV-2 in Myelodysplastic Syndromes: A Snapshot From Early Italian Experience

Author

Sandra Mossuto, Enrico Attardi, Francesco Alesiani, Emanuele Angelucci, Enrico Balleari, Massimo Bernardi, Gianni Binotto, Costanza Bosi, Anna Calvisi, Isabella Capodanno, Antonella Carbone, Andrea Castelli, Marco Cerrano, Rosanna Ciancia, Daniela Cilloni, Marino Clavio, Cristina Clissa, Elena Crisà, Monica Crugnola, Matteo G. Della Porta, Nicola Di Renzo, Ambra Di Veroli, Roberto Fattizzo, Carmen Fava, Susanna Fenu, Ida L. Ferrara, Luana Fianchi, Carla Filì, Carlo Finelli, Valentina Giai, Francesco Frattini, Valentina Gaidano, Gianluca Guaragna, Svitlana Gumenyuk, Roberto Latagliata, Stefano Mancini, Emanuela Messa, Alfredo Molteni, Pellegrino Musto, Pasquale Niscola, Esther Oliva, Giuseppe A. Palumbo, Annamaria Pelizzari, Federica Pilo, Antonella Poloni, Marta Riva, Flavia Rivellini, Chiara Sarlo, Mariarita Sciumé, Roberto Secchi, Carmine Selleri, Agostino Tafuri, and Valeria Santini

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2020
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5. Immunophenotypic analysis of erythroid dysplasia in myelodysplastic syndromes. A report from the IMDSFlow working group

Author

Theresia M. Westers, Eline M.P. Cremers, Uta Oelschlaegel, Ulrika Johansson, Peter Bettelheim, Sergio Matarraz, Alberto Orfao, Bijan Moshaver, Lisa Eidenschink Brodersen, Michael R. Loken, Denise A. Wells, Dolores Subirá, Matthew Cullen, Jeroen G. te Marvelde, Vincent H.J. van der Velden, Frank W.M.B. Preijers, Sung-Chao Chu, Jean Feuillard, Estelle Guérin, Katherina Psarra, Anna Porwit, Leonie Saft, Robin Ireland, Timothy Milne, Marie C. Béné, Birgit I. Witte, Matteo G. Della Porta, Wolfgang Kern, and Arjan A. van de Loosdrecht

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Current recommendations for diagnosing myelodysplastic syndromes endorse flow cytometry as an informative tool. Most flow cytometry protocols focus on the analysis of progenitor cells and the evaluation of the maturing myelomonocytic lineage. However, one of the most frequently observed features of myelodysplastic syndromes is anemia, which may be associated with dyserythropoiesis. Therefore, analysis of changes in flow cytometry features of nucleated erythroid cells may complement current flow cytometry tools. The multicenter study within the IMDSFlow Working Group, reported herein, focused on defining flow cytometry parameters that enable discrimination of dyserythropoiesis associated with myelodysplastic syndromes from non-clonal cytopenias. Data from a learning cohort were compared between myelodysplasia and controls, and results were validated in a separate cohort. The learning cohort comprised 245 myelodysplasia cases, 290 pathological, and 142 normal controls; the validation cohort comprised 129 myelodysplasia cases, 153 pathological, and 49 normal controls. Multivariate logistic regression analysis performed in the learning cohort revealed that analysis of expression of CD36 and CD71 (expressed as coefficient of variation), in combination with CD71 fluorescence intensity and the percentage of CD117+ erythroid progenitors provided the best discrimination between myelodysplastic syndromes and non-clonal cytopenias (specificity 90%; 95% confidence interval: 84–94%). The high specificity of this marker set was confirmed in the validation cohort (92%; 95% confidence interval: 86–97%). This erythroid flow cytometry marker combination may improve the evaluation of cytopenic cases with suspected myelodysplasia, particularly when combined with flow cytometry assessment of the myelomonocytic lineage.

Published
2017
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7. Inappropriately low hepcidin levels in patients with myelodysplastic syndrome carrying a somatic mutation of SF3B1

Author

Ilaria Ambaglio, Luca Malcovati, Elli Papaemmanuil, Coby M. Laarakkers, Matteo G. Della Porta, Anna Gallì, Matteo C. Da Vià, Elisa Bono, Marta Ubezio, Erica Travaglino, Riccardo Albertini, Peter J. Campbell, Dorine W. Swinkels, and Mario Cazzola

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Somatic mutations of the RNA splicing machinery have been recently identified in myelodysplastic syndromes. In particular, a strong association has been found between SF3B1 mutation and refractory anemia with ring sider-oblasts, a condition characterized by ineffective erythropoiesis and parenchymal iron overload. We studied the relationship between SF3B1 mutation, erythroid activity and hepcidin levels in myelodysplastic syndrome patients. Erythroid activity was evaluated through the proportion of marrow erythroblasts, soluble transferrin receptor and serum growth differentiation factor 15. Significant relationships were found between SF3B1 mutation and marrow erythroblasts (P=0.001), soluble transferrin receptor (P=0.003) and serum growth differentiation factor 15 (P=0.033). Serum hepcidin varied considerably, and multivariable analysis showed that the hepcidin to ferritin ratio, a measure of adequacy of hepcidin levels relative to body iron stores, was inversely related to the SF3B1 mutation (P=0.013). These observations suggest that patients with SF3B1 mutation have inappropriately low hepcidin levels, which may explain their propensity to parenchymal iron loading.

Published
2013
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8. Multicenter validation of a reproducible flow cytometric score for the diagnosis of low-grade myelodysplastic syndromes: results of a European LeukemiaNET study

Author

Matteo G. Della Porta, Cristina Picone, Cristiana Pascutto, Luca Malcovati, Hideto Tamura, Hiroshi Handa, Magdalena Czader, Sylvie Freeman, Paresh Vyas, Anna Porwit, Leonie Saft, Theresia M. Westers, Canan Alhan, Claudia Cali, Arjan A. van de Loosdrecht, and Kiyoyuki Ogata

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Background The current World Health Organization classification of myelodysplastic syndromes is based morphological evaluation of bone marrow dysplasia. In clinical practice, the reproducibility of the recognition of dysplasia is usually poor especially in cases that lack specific markers such as ring sideroblasts and clonal cytogenetic abnormalities.Design and Methods We aimed to develop and validate a flow cytometric score for the diagnosis of myelodysplastic syndrome. Four reproducible parameters were analyzed: CD34+ myeloblast-related and B-progenitor-related cluster size (defined by CD45 expression and side scatter characteristics CD34+ marrow cells), myeloblast CD45 expression and granulocyte side scatter value. The study comprised a “learning cohort” (n=538) to define the score and a “validation cohort” (n=259) to confirm its diagnostic value.Results With respect to non-clonal cytopenias, patients with myelodysplastic syndrome had increased myeloblast-related cluster size, decreased B-progenitor-related cluster size, aberrant CD45 expression and reduced granulocyte side scatter (P

Published
2012
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10. Impact of the degree of anemia on the outcome of patients with myelodysplastic syndrome and its integration into the WHO classification-based Prognostic Scoring System (WPSS)

Author

Luca Malcovati, Matteo G. Della Porta, Corinna Strupp, Ilaria Ambaglio, Andrea Kuendgen, Kathrin Nachtkamp, Erica Travaglino, Rosangela Invernizzi, Cristiana Pascutto, Mario Lazzarino, Ulrich Germing, and Mario Cazzola

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Background Anemia is an established negative prognostic factor in myelodysplastic syndromes but the relationship between its degree and clinical outcome is poorly defined. We, therefore, studied the relationship between severity of anemia and outcome in myelodysplastic syndrome patients.Design and Methods We studied 840 consecutive patients diagnosed with myelodysplastic syndromes at the Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, and 504 patients seen at the Heinrich-Heine-University Hospital, Düsseldorf, Germany. Hemoglobin levels were monitored longitudinally and analyzed by means of time-dependent Cox’s proportional hazards regression models.Results Hemoglobin levels lower than 9 g/dL in males (HR 5.56, P=0.018) and 8 g/dL in females (HR=5.35, P=0.026) were independently related to reduced overall survival, higher risk of non-leukemic death and cardiac death (P

Published
2011
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12. Risk stratification based on both disease status and extra-hematologic comorbidities in patients with myelodysplastic syndrome

Author

Matteo G. Della Porta, Luca Malcovati, Corinna Strupp, Ilaria Ambaglio, Andrea Kuendgen, Esther Zipperer, Erica Travaglino, Rosangela Invernizzi, Cristiana Pascutto, Mario Lazzarino, Ulrich Germing, and Mario Cazzola

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

The incidence of myelodysplastic syndromes increases with age and a high prevalence of co-morbid conditions has been reported in these patients. So far, risk assessment in myelodysplastic syndromes has been mainly based on disease status. We studied the prognostic impact of comorbidity on the natural history of myelodysplastic syndrome with the aim of developing novel tools for risk assessment. The study population included a learning cohort of 840 patients diagnosed with myelodysplastic syndrome in Pavia, Italy, and a validation cohort of 504 patients followed in Duesseldorf, Germany. Information on comorbidity was extracted from detailed review of the patients’ medical charts and laboratory values at diagnosis and during the course of the disease. Univariable and multivariable survival analyses with both fixed and time-dependent covariates were performed using Cox’s proportional hazards regression models. Comorbidity was present in 54% of patients in the learning cohort. Cardiac disease was the most frequent comorbidity and the main cause of non-leukemic death. In multivariable analysis, comorbidity had a significant impact on both non-leukemic death (P=0.01) and overall survival (P=0.02). Cardiac, liver, renal, pulmonary disease and solid tumors were found to independently affect the risk of non-leukemic death. A time-dependent myelodysplastic syndrome-specific comorbidity index (MDS-CI) was developed for predicting the effect of comorbidity on outcome. This identified three groups of patients which showed significantly different probabilities of non-leukemic death (P

Published
2011
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13. Prevalence, incidence and types of mild anemia in the elderly: the 'Health and Anemia' population-based study

Author

Mauro Tettamanti, Ugo Lucca, Francesca Gandini, Angela Recchia, Paola Mosconi, Giovanni Apolone, Alessandro Nobili, Maria Vittoria Tallone, Paolo Detoma, Adriano Giacomin, Mario Clerico, Patrizia Tempia, Luigi Savoia, Gilberto Fasolo, Luisa Ponchio, Matteo G. Della Porta, and Emma Riva

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Background Hemoglobin concentrations slightly below the lower limit of normal are a common laboratory finding in the elderly, but scant evidence is available on the actual occurrence of mild anemia despite its potential effect on health. The objectives of this study were to estimate the prevalence and incidence of mild grade anemia and to assess the frequency of anemia types in the elderly.Design and Methods This was a prospective, population-based study in all residents 65 years or older in Biella, Italy.Results Blood test results were available for analysis from 8,744 elderly. Hemoglobin concentration decreased and mild anemia increased steadily with increasing age. Mild anemia (defined as a hemoglobin concentration of 10.0–11.9 g/dL in women and 10.0–12.9 g/dL in men) affected 11.8% of the elderly included in the analysis, while the estimated prevalence in the entire population was 11.1%. Before hemoglobin determination, most mildly anemic individuals perceived themselves as non-anemic. Chronic disease anemia, thalassemia trait, and renal insufficiency were the most frequent types of mild anemia. The underlying cause of mild anemia remained unexplained in 26.4% of the cases, almost one third of which might be accounted for by myelodysplastic syndromes. In a random sample of non-anemic elderly at baseline (n=529), after about 2 years, the annual incidence rate of mild anemia was 22.5 per 1000 person-years and increased with increasing age.Conclusions The prevalence and incidence of mild anemia increase with age and mild anemia affects more than one out of ten elderly individuals. Unexplained anemia is common and may be due to myelodysplastic syndromes in some cases.

Published
2010
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14. Standardization of flow cytometry in myelodysplastic syndromes: report from the first European LeukemiaNet working conference on flow cytometry in myelodysplastic syndromes

Author

Arjan A. van de Loosdrecht, Canan Alhan, Marie Christine Béné, Matteo G. Della Porta, Angelika M. Dräger, Jean Feuillard, Patricia Font, Ulrich Germing, Detlef Haase, Christa H. Homburg, Robin Ireland, Joop H. Jansen, Wolfgang Kern, Luca Malcovati, Jeroen G. te Marvelde, Ghulam J. Mufti, Kiyoyuki Ogata, Alberto Orfao, Gert J. Ossenkoppele, Anna Porwit, Frank W. Preijers, Stephen J. Richards, Gerrit Jan Schuurhuis, Dolores Subirá, Peter Valent, Vincent H.J. van der Velden, Paresh Vyas, August H. Westra, Theo M. de Witte, Denise A. Wells, Michael R. Loken, and Theresia M. Westers

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

The myelodysplastic syndromes are a group of clonal hematopoietic stem cell diseases characterized by cytopenia(s), dysplasia in one or more cell lineages and increased risk of evolution to acute myeloid leukemia (AML). Recent advances in immunophenotyping of hematopoietic progenitor and maturing cells in dysplastic bone marrow point to a useful role for multiparameter flow cytometry (FCM) in the diagnosis and prognostication of myelodysplastic syndromes. In March 2008, representatives from 18 European institutes participated in a European LeukemiaNet (ELN) workshop held in Amsterdam as a first step towards standardization of FCM in myelodysplastic syndromes. Consensus was reached regarding standard methods for cell sampling, handling and processing. The group also defined minimal combinations of antibodies to analyze aberrant immunophenotypes and thus dysplasia. Examples are altered numbers of CD34+ precursors, aberrant expression of markers on myeloblasts, maturing myeloid cells, monocytes or erythroid precursors and the expression of lineage infidelity markers. When applied in practice, aberrant FCM patterns correlate well with morphology, the subclassification of myelodysplastic syndromes, and prognostic scoring systems. However, the group also concluded that despite strong evidence for an impact of FCM in myelodysplastic syndromes, further (prospective) validation of markers and immunophenotypic patterns are required against control patient groups as well as further standardization in multi-center studies. Standardization of FCM in myelodysplastic syndromes may thus contribute to improved diagnosis and prognostication of myelodysplastic syndromes in the future.

Published
2009
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15. Diagnostic utility of flow cytometry in low-grade myelodysplastic syndromes: a prospective validation study

Author

Kiyoyuki Ogata, Matteo G. Della Porta, Luca Malcovati, Cristina Picone, Norio Yokose, Akira Matsuda, Taishi Yamashita, Hideto Tamura, Junichi Tsukada, and Kazuo Dan

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Background The diagnosis of myelodysplastic syndromes is not always straightforward when patients lack specific diagnostic markers, such as blast excess, karyotype abnormality, and ringed sideroblasts.Design and Methods We designed a flow cytometry protocol applicable in many laboratories and verified its diagnostic utility in patients without those diagnostic markers. The cardinal parameters, analyzable from one cell aliquot, were myeloblasts (%), B-cell progenitors (%), myeloblast CD45 expression, and channel number of side scatter where the maximum number of granulocytes occurs. The adjunctive parameters were CD11b, CD15, and CD56 expression (%) on myeloblasts. Marrow samples from 106 control patients with cytopenia and 134 low-grade myelodysplastic syndromes patients, including 81 lacking both ringed sideroblasts and cytogenetic aberrations, were prospectively analyzed in Japan and Italy.Results Data outside the predetermined reference range in 2 or more parameters (multiple abnormalities) were common in myelodysplastic syndromes patients. In those lacking ringed sideroblasts and cytogenetic aberrations, multiple abnormalities were observed in 8/26 Japanese (30.8%) and 37/55 Italians (67.3%) when the cardinal parameters alone were considered, and in 17/26 Japanese (65.4%) and 42/47 Italians (89.4%) when all parameters were taken into account. Multiple abnormalities were rare in controls. When data from all parameters were used, the diagnostic sensitivities were 65% and 89%, specificities were 98% and 90%, and likelihood ratios were 28.1 and 8.5 for the Japanese and Italian cohorts, respectively.Conclusions This protocol can be used in the diagnostic work-up of low-grade myelodysplastic syndromes patients who lack specific diagnostic markers, although further improvement in diagnostic power is desirable.

Published
2009
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16. Genome-wide analysis of copy number changes and loss of heterozygosity in myelodysplastic syndrome with del(5q) using high-density single nucleotide polymorphism arrays

Author

Li Wang, Carrie Fidler, Nandita Nadig, Aristoteles Giagounidis, Matteo G. Della Porta, Luca Malcovati, Sally Killick, Norbert Gattermann, Carlo Aul, Jacqueline Boultwood, and James S. Wainscoat

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Background We undertook a genome wide single nucleotide polymorphism analysis of a spectrum of patients with myelodysplastic syndrome del(5q) in order to investigate whether additional genomic abnormalities occur. Single nucleotide polymorphism array analysis has been shown to detect not only gene deletions but also regions of uniparental disomy that can pinpoint particular regions for mutation analysis.Design and Methods We studied 42 cases of myelodysplastic syndrome with del(5q), comprising 21 patients with 5q- syndrome and 21 with del(5q) (not 5q- syndrome), and 45 healthy controls by genome wide single nucleotide polymorphism analysis with the 50K Affymetrix single nucleotide polymorphism arrays.Results The del(5q) was characterized in all cases. The commonly deleted region of the 5q- syndrome extends between the genes SH3TC2 (proximal boundary) and GLRA1 (distal boundary) and measures 2.9 Mb. Copy number changes in addition to the del(5q) were observed in 10 of 21 patients with del(5q) myelodysplastic syndrome but in none of the patients with the 5q- syndrome. A total of 63 regions of uniparental disomy greater than 2 Mb were detected in 40 of 42 patients, dispersed on 18/23 chromosomes. In the 5q- syndrome group 31 regions of uniparental disomy were identified in 19 of 21 patients, the largest one being 7.6 Mb. All 21 patients with del(5q) myelodysplastic syndrome had uniparental disomy; in total 32 regions of uniparental disomy were identified in the 21 patients, including six regions of uniparental disomy > 10 Mb. Eight recurrent regions of uniparental disomy were observed among the 42 patients. For eight patients we had T-cell DNA as a germline control and four recurrent regions of uniparental disomy were identified that were present only in the neutrophil and not T-cell DNA. One small region of uniparental disomy at 10p12.31-p12.2 was observed in four patients with the 5q- syndrome.Conclusions This study shows that regions of uniparental disomy greater than 2 Mb are found in the 5q-syndrome and del(5q) myelodysplastic syndrome, although large regions of uniparental disomy (>10 Mb) are only found in the latter group. The recurrent regions of uniparental disomy may indicate the position of novel leukemia-associated genes.

Published
2008
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18. A sex-informed approach to improve the personalised decision making process in myelodysplastic syndromes

Author

Giulia Maggioni, Matteo Bersanelli, Erica Travaglino, Ana Alfonso Piérola, Annika Kasprzak, Arnan Sangerman Montserrat, Elisabetta Sauta, Claudia Sala, Tommaso Matteuzzi, Manja Meggendorfer, Matteo Gnocchi, Lin-Pierre Zhao, Cristina Astrid Tentori, Kathrin Nachtkamp, Daniele Dall'Olio, Ettore Mosca, Marta Ubezio, Alessia Campagna, Antonio Russo, Giulia Rivoli, Massimo Bernardi, Lorenza Borin, Maria Teresa Voso, Marta Riva, Esther Oliva, Matteo Zampini, Elena Riva, Elena Saba, Saverio D'Amico, Luca Lanino, Benedetta Tinterri, Francesca Re, Marilena Bicchieri, Laura Giordano, Giovanni Angelotti, Pierandrea Morandini, Anne Sophie Kubasch, Francesco Passamonti, Alessandro Rambaldi, Victor Savevski, Armando Santoro, Arjan A. van de Loosdrecht, Alice Brogi, Valeria Santini, Shahram Kordasti, Guillermo Sanz, Francesc Sole, Norbert Gattermann, Wolfgang Kern, Uwe Platzbecker, Lionel Ades, Pierre Fenaux, Torsten Haferlach, Gastone Castellani, Ulrich Germing, Maria Diez-Campelo, Matteo G. Della Porta, Hematology, AII - Cancer immunology, AII - Inflammatory diseases, CCA - Cancer biology and immunology, Maggioni, G, Bersanelli, M, Travaglino, E, Alfonso Piérola, A, Kasprzak, A, Sangerman Montserrat, A, Sauta, E, Sala, C, Matteuzzi, T, Meggendorfer, M, Gnocchi, M, Zhao, L, Astrid Tentori, C, Nachtkamp, K, Dall'Olio, D, Mosca, E, Ubezio, M, Campagna, A, Russo, A, Rivoli, G, Bernardi, M, Borin, L, Teresa Voso, M, Riva, M, Oliva, E, Zampini, M, Riva, E, Saba, E, D'Amico, S, Lanino, L, Tinterri, B, Re, F, Bicchieri, M, Giordano, L, Angelotti, G, Morandini, P, Sophie Kubasch, A, Passamonti, F, Rambaldi, A, Savevski, V, Santoro, A, A van de Loosdrecht, A, Brogi, A, Santini, V, Kordasti, S, Sanz, G, Sole, F, Gattermann, N, Kern, W, Platzbecker, U, Ades, L, Fenaux, P, Haferlach, T, Castellani, G, Germing, U, Diez-Campelo, M, and G Della Porta, M

Subjects
Malalties hematològiques, Hematologic diseases, Myelodysplastic Syndrome, Factors sexuals en les malalties, Sex factors in disease, sex, Hematology, personalized medicine, Settore MED/15
Abstract

Background Sex is a major source of diversity among patients and a sex-informed approach is becoming a new paradigm in precision medicine. We aimed to describe sex diversity in myelodysplastic syndromes in terms of disease genotype, phenotype, and clinical outcome. Moreover, we sought to incorporate sex information into the clinical decision-making process as a fundamental component of patient individuality. Methods In this multicentre, observational cohort study, we retrospectively analysed 13 284 patients aged 18 years or older with a diagnosis of myelodysplastic syndrome according to 2016 WHO criteria included in the EuroMDS network (n=2025), International Working Group for Prognosis in MDS (IWG-PM; n=2387), the Spanish Group of Myelodysplastic Syndromes registry (GESMD; n=7687), or the Dusseldorf MDS registry (n=1185). Recruitment periods for these cohorts were between 1990 and 2016. The correlation between sex and genomic features was analysed in the EuroMDS cohort and validated in the IWG-PM cohort. The effect of sex on clinical outcome, with overall survival as the main endpoint, was analysed in the EuroMDS population and validated in the other three cohorts. Finally, novel prognostic models incorporating sex and genomic information were built and validated, and compared to the widely used revised International Prognostic Scoring System (IPSS-R). This study is registered with ClinicalTrials.gov, NCT04889729. Findings The study included 7792 (58middot7%) men and 5492 (41middot3%) women. 10 906 (82middot1%) patients were White, and race was not reported for 2378 (17middot9%) patients. Sex biases were observed at the single-gene level with mutations in seven genes enriched in men (ASXL1, SRSF2, and ZRSR2 p

Published
2023

19. Multiparameter flow cytometry in the evaluation of myelodysplasia

Author

Anna Porwit, Marie C. Béné, Carolien Duetz, Sergio Matarraz, Uta Oelschlaegel, Theresia M. Westers, Orianne Wagner‐Ballon, Shahram Kordasti, Peter Valent, Frank Preijers, Canan Alhan, Frauke Bellos, Peter Bettelheim, Kate Burbury, Nicolas Chapuis, Eline Cremers, Matteo G. Della Porta, Alan Dunlop, Lisa Eidenschink‐Brodersen, Patricia Font, Michaela Fontenay, Willemijn Hobo, Robin Ireland, Ulrika Johansson, Michael R. Loken, Kiyoyuki Ogata, Alberto Orfao, Katherina Psarra, Leonie Saft, Dolores Subira, Jeroen te Marvelde, Denise A. Wells, Vincent H. J. van der Velden, Wolfgang Kern, and Arjan A. van de Loosdrecht

Subjects
All institutes and research themes of the Radboud University Medical Center, Histology, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], Cell Biology, Pathology and Forensic Medicine
Abstract

Contains fulltext : 290820.pdf (Publisher’s version ) (Open Access) Multiparameter flow cytometry (MFC) is one of the essential ancillary methods in bone marrow (BM) investigation of patients with cytopenia and suspected myelodysplastic syndrome (MDS). MFC can also be applied in the follow-up of MDS patients undergoing treatment. This document summarizes recommendations from the International/European Leukemia Net Working Group for Flow Cytometry in Myelodysplastic Syndromes (ELN iMDS Flow) on the analytical issues in MFC for the diagnostic work-up of MDS. Recommendations for the analysis of several BM cell subsets such as myeloid precursors, maturing granulocytic and monocytic components and erythropoiesis are given. A core set of 17 markers identified as independently related to a cytomorphologic diagnosis of myelodysplasia is suggested as mandatory for MFC evaluation of BM in a patient with cytopenia. A myeloid precursor cell (CD34(+) CD19(-) ) count >3% should be considered immunophenotypically indicative of myelodysplasia. However, MFC results should always be evaluated as part of an integrated hematopathology work-up. Looking forward, several machine-learning-based analytical tools of interest should be applied in parallel to conventional analytical methods to investigate their usefulness in integrated diagnostics, risk stratification, and potentially even in the evaluation of response to therapy, based on MFC data. In addition, compiling large uniform datasets is desirable, as most of the machine-learning-based methods tend to perform better with larger numbers of investigated samples, especially in such a heterogeneous disease as MDS. 01 januari 2023

Published
2023

21. Efficacy and Safety of Luspatercept in Adult Patients with Transfusion-Dependent Anemia Due to Very Low, Low and Intermediate Risk Myelodysplastic Syndromes (MDS) with Ring Sideroblasts, Who Had an Unsatisfactory Response to or Are Ineligible for Erythropoietin-Based Therapy: A Retrospective Multicenter Study By Fondazione Italiana Sindromi Mielodisplastiche (FiSiM ETS)

Author

Luca Lanino, Prassede Salutari, Alessandra Perego, Bruno Fattizzo, Marta Riva, Marta Ubezio, Pellegrino Musto, Daniela Cilloni, Esther Natalie Oliva, Maria Teresa Voso, Anna Maria Pelizzari, Antonella Poloni, Isabella Capodanno, Chiara Elena, Claudio Fozza, Fabrizio Pane, Massimo Breccia, Marco De Gobbi, Francesco Di Bassiano, Daniela Barraco, Elena Crisà, Dario Ferrero, Chiara Frairia, Antonella Vaccarino, Davide Griguolo, Stefania Paolini, Martina Quintini, Mariarosaria Sessa, Mauro Turrini, Monica Bocchia, Nicola Di Renzo, Elisa Diral, Cristina Foli, Alfredo Molteni, Ubaldo Occhini, Giulia Rivoli, Carmine Selleri, Roberto Bono, Anna Calvisi, Andrea Castelli, Eros Di Bona, Ambra Di Veroli, Luana Fianchi, Sara Galimberti, Daniele Grimaldi, Monia Marchetti, Marianna Norata, Alessandro Rambaldi, Ilaria Tanasi, Patrizia Tosi, Ilaria Naldi, Valeria Santini, and Matteo G. Della Porta

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

22. Clinical Implications of p53 Dysfunction in Patients with Myelodysplastic Syndromes

Author

Elena Riva, Matteo Zampini, Termanini Alberto, Lorenzo Dall'Olio, Alessandra Merlotti, Austin Kulasekararaj, Michela Calvi, Clara Di Vito, Daoud Rahal, Arturo Bonometti, Giorgio Croci, Emanuela Boveri, Umberto Gianelli, Maurilio Ponzoni, Antonio Russo, Benedetta Tinterri, Francesca Re, Elisabetta Sauta, Elena Saba, Erica Travaglino, Marta Ubezio, Alessia Campagna, Luca Lanino, Giulia Maggioni, Cristina Astrid Tentori, Chiara Milanesi, Nicla Manes, Saverio D'Amico, Francesca Ficara, Laura Crisafulli, Domenico Mavilio, Enrico Lugli, Armando Santoro, Maria Diez-Campelo, Guillermo Sanz, Francesc Solé, Uwe Platzbecker, Valeria Santini, Shahram Kordasti, Pierre Fenaux, Torsten Haferlach, Daniel Remondini, Castellani Gastone, and Matteo G. Della Porta

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

23. Long-Term Follow-up of AML Patients Treated Intensively before the Era of Targeted Agents. a Big Data Analysis from the Harmony Collaboration

Author

Marta Anna Sobas, Angela Villaverde Ramiro, Alberto Hernández Sánchez, Javier Martinez Elicegui, Teresa González, Raúl Azibeiro Melchor, María Abáigar, Laura Tur, Daniele Dall'Olio, Eric Sträng, Jesse M. Tettero, Castellani Gastone, Axel Benner, Konstanze Döhner, Christian Thiede, Amin T. Turki, Klaus H. Metzeler, Torsten Haferlach, Frederick Damm, Rosa Ayala, Joaquín Martínez-López, Ken I Mills, Jorge Sierra, Sören Lehmann, Matteo G. Della Porta, Jiri Mayer, Dirk Reinhardt, Rubén Villoria Medina, Renate Schulze-Rath, Martje Barbus, Jesús María Hernández-Rivas, Brian James Patrick Huntly, Gert Ossenkoppele, Hartmut Dohner, and Lars Bullinger

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

24. Multi-Modal Analysis and Federated Learning Approach for Classification and Personalized Prognostic Assessment in Myeloid Neoplasms

Author

Saverio D'Amico, Lorenzo Dall'Olio, Cesare Rollo, Patricia Alonso, Iñigo Prada-Luengo, Daniele Dall'Olio, Claudia Sala, Matteo Bersanelli, Elisabetta Sauta, Marilena Bicchieri, Pierandrea Morandini, Tobia Tommasini, Victor Savevski, Lin-Pierre Zhao, Uwe Platzbecker, Maria Diez-Campelo, Valeria Santini, Pierre Fenaux, Torsten Haferlach, Anders Krogh, Santiago Zazo, Piero Fariselli, Tiziana Sanavia, Matteo G. Della Porta, and Castellani Gastone

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

25. Synthetic Data Generation By Artificial Intelligence to Accelerate Translational Research and Precision Medicine in Hematological Malignancies

Author

Saverio D'Amico, Elisabetta Sauta, Matteo Bersanelli, Daniele Dall'Olio, Claudia Sala, Lorenzo Dall'Olio, Pierandrea Morandini, Tobia Tommasini, Marilena Bicchieri, Matteo Zampini, Victor Savevski, Iñigo Prada-Luengo, Anders Krogh, Uwe Platzbecker, Maria Diez-Campelo, Valeria Santini, Pierre Fenaux, Torsten Haferlach, Castellani Gastone, and Matteo G. Della Porta

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

27. Gimema AML1718 Part 1: Planned Interim Analysis of a Safety Run-in and Phase 2 Open-Label Study of Venetoclax, Fludarabine, Idarubicin and Cytarabine (V-FLAI) in the Induction Therapy of Non Low-Risk Acute Myeloid Leukemia

Author

Giovanni Marconi, Alfonso Piciocchi, Ernesta Audisio, Giorgio Priolo, Cristina Papayannidis, Maurizio Martelli, Francesca Paoloni, Roberto Massimo Lemoli, Monica Bocchia, Francesco Lanza, Albana Lico, Fabio Ciceri, Matteo G. Della Porta, Marco Frigeni, Luisa Giaccone, Germana Beltrami, Erika Borlenghi, Maria Chiara Di Chio, Carmine Selleri, Enrico Crea, Irene Urbino, Chiara Sartor, Clara Minotti, Fabio Guolo, Edoardo La Sala, Jacopo Nanni, Giorgia Simonetti, Maria Teresa Bochicchio, Giuseppe Saglio, Adriano Venditti, Marco Vignetti, Paola Fazi, and Giovanni Martinelli

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

28. Dynamics of Mortality and Transformation Risk within Different Risk Groups of Patients with Myelodysplastic Syndromes Stratified According to the IPSS-R - Comparison of Treated and Untreated Patients and Consequences for the Description of Risk Categories

Author

Michael Pfeilstocker, Heinz Tuechler, Lionel Ades, Jaroslav Cermak, Fatiha Chermat, Matteo G. Della Porta, Pierre Fenaux, Guillermo Garcia-Manero, Ulrich Germing, Detlef Haase, Andrea Kuendgen, Michael Luebbert, Silvia Maria Meira Magalhaes, Luca Malcovati, Yasushi Miyazaki, Guillermo Sanz, Valeria Santini, Mikkael A. Sekeres, Matthew J Walter, Peter Valent, and Peter L Greenberg

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

29. A sex-informed approach to improve the personalised decision making process in myelodysplastic syndromes: a multicentre, observational cohort study

Author

Maggioni, G, Bersanelli, M, Travaglino, E, Alfonso Piérola, A, Kasprzak, A, Sangerman Montserrat, A, Sauta, E, Sala, C, Matteuzzi, T, Meggendorfer, M, Gnocchi, M, Zhao, L, Astrid Tentori, C, Nachtkamp, K, Dall'Olio, D, Mosca, E, Ubezio, M, Campagna, A, Russo, A, Rivoli, G, Bernardi, M, Borin, L, Teresa Voso, M, Riva, M, Oliva, E, Zampini, M, Riva, E, Saba, E, D'Amico, S, Lanino, L, Tinterri, B, Re, F, Bicchieri, M, Giordano, L, Angelotti, G, Morandini, P, Sophie Kubasch, A, Passamonti, F, Rambaldi, A, Savevski, V, Santoro, A, A van de Loosdrecht, A, Brogi, A, Santini, V, Kordasti, S, Sanz, G, Sole, F, Gattermann, N, Kern, W, Platzbecker, U, Ades, L, Fenaux, P, Haferlach, T, Castellani, G, Germing, U, Diez-Campelo, M, G Della Porta, M, Giulia Maggioni, Matteo Bersanelli, Erica Travaglino, Ana Alfonso Piérola, Annika Kasprzak, Arnan Sangerman Montserrat, Elisabetta Sauta, Claudia Sala, Tommaso Matteuzzi, Manja Meggendorfer, Matteo Gnocchi, Lin-Pierre Zhao, Cristina Astrid Tentori, Kathrin Nachtkamp, Daniele Dall'Olio, Ettore Mosca, Marta Ubezio, Alessia Campagna, Antonio Russo, Giulia Rivoli, Massimo Bernardi, Lorenza Borin, Maria Teresa Voso, Marta Riva, Esther Oliva, Matteo Zampini, Elena Riva, Elena Saba, Saverio D'Amico, Luca Lanino, Benedetta Tinterri, Francesca Re, Marilena Bicchieri, Laura Giordano, Giovanni Angelotti, Pierandrea Morandini, Anne Sophie Kubasch, Francesco Passamonti, Alessandro Rambaldi, Victor Savevski, Armando Santoro, Arjan A van de Loosdrecht, Alice Brogi, Valeria Santini, Shahram Kordasti, Guillermo Sanz, Francesc Sole, Norbert Gattermann, Wolfgang Kern, Uwe Platzbecker, Lionel Ades, Pierre Fenaux, Torsten Haferlach, Gastone Castellani, Ulrich Germing, Maria Diez-Campelo, Matteo G Della Porta, Maggioni, G, Bersanelli, M, Travaglino, E, Alfonso Piérola, A, Kasprzak, A, Sangerman Montserrat, A, Sauta, E, Sala, C, Matteuzzi, T, Meggendorfer, M, Gnocchi, M, Zhao, L, Astrid Tentori, C, Nachtkamp, K, Dall'Olio, D, Mosca, E, Ubezio, M, Campagna, A, Russo, A, Rivoli, G, Bernardi, M, Borin, L, Teresa Voso, M, Riva, M, Oliva, E, Zampini, M, Riva, E, Saba, E, D'Amico, S, Lanino, L, Tinterri, B, Re, F, Bicchieri, M, Giordano, L, Angelotti, G, Morandini, P, Sophie Kubasch, A, Passamonti, F, Rambaldi, A, Savevski, V, Santoro, A, A van de Loosdrecht, A, Brogi, A, Santini, V, Kordasti, S, Sanz, G, Sole, F, Gattermann, N, Kern, W, Platzbecker, U, Ades, L, Fenaux, P, Haferlach, T, Castellani, G, Germing, U, Diez-Campelo, M, G Della Porta, M, Giulia Maggioni, Matteo Bersanelli, Erica Travaglino, Ana Alfonso Piérola, Annika Kasprzak, Arnan Sangerman Montserrat, Elisabetta Sauta, Claudia Sala, Tommaso Matteuzzi, Manja Meggendorfer, Matteo Gnocchi, Lin-Pierre Zhao, Cristina Astrid Tentori, Kathrin Nachtkamp, Daniele Dall'Olio, Ettore Mosca, Marta Ubezio, Alessia Campagna, Antonio Russo, Giulia Rivoli, Massimo Bernardi, Lorenza Borin, Maria Teresa Voso, Marta Riva, Esther Oliva, Matteo Zampini, Elena Riva, Elena Saba, Saverio D'Amico, Luca Lanino, Benedetta Tinterri, Francesca Re, Marilena Bicchieri, Laura Giordano, Giovanni Angelotti, Pierandrea Morandini, Anne Sophie Kubasch, Francesco Passamonti, Alessandro Rambaldi, Victor Savevski, Armando Santoro, Arjan A van de Loosdrecht, Alice Brogi, Valeria Santini, Shahram Kordasti, Guillermo Sanz, Francesc Sole, Norbert Gattermann, Wolfgang Kern, Uwe Platzbecker, Lionel Ades, Pierre Fenaux, Torsten Haferlach, Gastone Castellani, Ulrich Germing, Maria Diez-Campelo, and Matteo G Della Porta

Abstract

BACKGROUND: Sex is a major source of diversity among patients and a sex-informed approach is becoming a new paradigm in precision medicine. We aimed to describe sex diversity in myelodysplastic syndromes in terms of disease genotype, phenotype, and clinical outcome. Moreover, we sought to incorporate sex information into the clinical decision-making process as a fundamental component of patient individuality. METHODS: In this multicentre, observational cohort study, we retrospectively analysed 13 284 patients aged 18 years or older with a diagnosis of myelodysplastic syndrome according to 2016 WHO criteria included in the EuroMDS network (n=2025), International Working Group for Prognosis in MDS (IWG-PM; n=2387), the Spanish Group of Myelodysplastic Syndromes registry (GESMD; n=7687), or the Düsseldorf MDS registry (n=1185). Recruitment periods for these cohorts were between 1990 and 2016. The correlation between sex and genomic features was analysed in the EuroMDS cohort and validated in the IWG-PM cohort. The effect of sex on clinical outcome, with overall survival as the main endpoint, was analysed in the EuroMDS population and validated in the other three cohorts. Finally, novel prognostic models incorporating sex and genomic information were built and validated, and compared to the widely used revised International Prognostic Scoring System (IPSS-R). This study is registered with ClinicalTrials.gov, NCT04889729. FINDINGS: The study included 7792 (58·7%) men and 5492 (41·3%) women. 10 906 (82·1%) patients were White, and race was not reported for 2378 (17·9%) patients. Sex biases were observed at the single-gene level with mutations in seven genes enriched in men (ASXL1, SRSF2, and ZRSR2 p<0·0001 in both cohorts; DDX41 not available in the EuroMDS cohort vs p=0·0062 in the IWG-PM cohort; IDH2 p<0·0001 in EuroMDS vs p=0·042 in IWG-PM; TET2 p=0·031 vs p=0·035; U2AF1 p=0·033 vs p<0·0001) and mutations in two genes were enriched in women (DNMT3A p<0·000

Published
2023

30. Flow cytometric analysis of myelodysplasia: Pre-analytical and technical issues—Recommendations from the European LeukemiaNet

Author

Vincent H. J. van der Velden, Frank Preijers, Ulrika Johansson, Theresia M. Westers, Alan Dunlop, Anna Porwit, Marie C. Béné, Peter Valent, Jeroen te Marvelde, Orianne Wagner‐Ballon, Uta Oelschlaegel, Leonie Saft, Sharham Kordasti, Robin Ireland, Eline Cremers, Canan Alhan, Carolien Duetz, Willemijn Hobo, Nicolas Chapuis, Michaela Fontenay, Peter Bettelheim, Lisa Eidenshink‐Brodersen, Patricia Font, Michael R. Loken, Sergio Matarraz, Kiyoyuki Ogata, Alberto Orfao, Katherina Psarra, Dolores Subirá, Denise A. Wells, Matteo G. Della Porta, Kate Burbury, Frauke Bellos, Elisabeth Weiß, Wolfgang Kern, Arjan van de Loosdrecht, Hematology laboratory, Internal medicine, Hematology, VU University medical center, AII - Cancer immunology, CCA - Cancer biology and immunology, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Radboudumc Nijmegen [The Netherlands], University Hospitals Bristol, Amsterdam UMC - Amsterdam University Medical Center, Royal Marsden Hospital [Surrey, UK], Lund University [Lund], Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Medizinische Universität Wien = Medical University of Vienna, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Henri Mondor, University Hospital Carl Gustav Carus [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Karolinska Institutet [Stockholm], King‘s College London, Maastricht University [Maastricht], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Ordensklinikum Linz Elisabethinen, HematoLogics, Inc. [Seattle, WA, USA], Hospital General Universitario 'Gregorio Marañón' [Madrid], Universidad de Salamanca, Instituto de Salud Carlos III [Madrid] (ISC), Metropolitan Research and Treatment Centre for Blood Disorders [Tokyo, Japan] (MRTC Japan), Evangelismos Athens General Hospital, Universidad de Guadalajara, Humanitas University [Milan] (Hunimed), University of Melbourne, Munich Leukemia Laboratory [Munich, Germany], MUMC+: MA Med Staf Artsass Interne Geneeskunde (9), RS: FHML non-thematic output, Immunology, and Bernardo, Elizabeth

Subjects
Histology, MASTOCYTOSIS, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], BONE-MARROW, DIAGNOSTIC-CRITERIA, [SDV.CAN]Life Sciences [q-bio]/Cancer, REFRACTORY CYTOPENIA, CLASSIFICATION, Pathology and Forensic Medicine, pre-analytic issues, 03 medical and health sciences, 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, [SDV.CAN] Life Sciences [q-bio]/Cancer, SDG 3 - Good Health and Well-being, hemic and lymphatic diseases, MDS, 030304 developmental biology, 0303 health sciences, flow cytometry, Cell Biology, QUANTIFICATION, LOW-GRADE, 3. Good health, CONSENSUS STATEMENTS, ELN, 030215 immunology, STANDARDS
Abstract

Contains fulltext : 290818.pdf (Publisher’s version ) (Open Access) BACKGROUND: Flow cytometry (FCM) aids the diagnosis and prognostic stratification of patients with suspected or confirmed myelodysplastic syndrome (MDS). Over the past few years, significant progress has been made in the FCM field concerning technical issues (including software and hardware) and pre-analytical procedures. METHODS: Recommendations are made based on the data and expert discussions generated from 13 yearly meetings of the European LeukemiaNet international MDS Flow working group. RESULTS: We report here on the experiences and recommendations concerning (1) the optimal methods of sample processing and handling, (2) antibody panels and fluorochromes, and (3) current hardware technologies. CONCLUSIONS: These recommendations will support and facilitate the appropriate application of FCM assays in the diagnostic workup of MDS patients. Further standardization and harmonization will be required to integrate FCM in MDS diagnostic evaluations in daily practice. 01 januari 2023

Published
2023

31. <scp>ELN iMDS</scp> flow working group validation of the monocyte assay for chronic myelomonocytic leukemia diagnosis by flow cytometry

Author

Sergio Matarraz, Ulrika Johansson, Matteo G. Della Porta, Katherina Psarra, Erica Travaglino, Irene Nuevo, Monali Gupta, Sihem Tarfi, Arjan A. van de Loosdrecht, Dolores Subirá, Orianne Wagner-Ballon, Wolfgang Kern, Frauke Bellos, Enrique Colado, Jeroen Lauf, Peter Bettelheim, Theresia M. Westers, Robin M. Ireland, Serafeim Karathanos, Hematology laboratory, Hematology, and CCA - Cancer biology and immunology

Subjects
Pathology, medicine.medical_specialty, Histology, medicine.diagnostic_test, business.industry, Monocyte, Immunology, Chronic myelomonocytic leukemia, Hematology, Cell Biology, medicine.disease, Biochemistry, Flow cytometry, Pathology and Forensic Medicine, medicine.anatomical_structure, Flow (mathematics), medicine, business
Abstract

Introduction It was proposed that peripheral blood (PB) monocyte subset analysis evaluated by flow cytometry, hereafter referred to as "monocyte assay", could rapidly and efficiently distinguish chronic myelomonocytic leukemia (CMML) from other causes of monocytosis by highlighting an increase in the classical monocyte (cMo) fraction above 94%. However, the robustness of this assay required a large multicenter validation. Methods PB and/or bone marrow (BM) samples from adult patients displaying monocytosis were assessed with the "monocyte assay" by ten ELN iMDS Flow working group centers (6 equipped with BD FACSCanto™ II (BD Biosciences), 3 with Navios™ (Beckman Coulter) and one with BD™ LSRII (BD Biosciences)) with harmonized protocols. The corresponding files were reanalyzed in a blind fashion by a skilled operator and the cMo (CD14 ++CD16 -) percentages obtained by both analyses were compared. Information regarding age, gender, complete blood count, marrow cytomorphology, cytogenetics and molecular analysis was collected. Confirmed diagnoses were collected when available as well as follow-up for CMML patients. Results The comparison between cMo percentages from 267 PB files provided by the 10 centers and the centralized cMo percentages showed a good global significant correlation (r=0.88; p The second aim of this multicenter study was to assess the feasibility of the monocyte assay on 117 BM samples provided by 7 out of the 10 ELN centers, 43 of which being paired to PB samples. The comparison between cMo percentages provided by the 7 centers and the centralized cMo percentages showed a lower global significant correlation compared to PB samples (r=0.74; p Conclusions This ELN multicenter study demonstrates the robustness of the monocyte assay with only limited variability of cMo percentages, validates the 94% cutoff value, confirms its high sensitivity and specificity in PB and finally, also confirms the possibility of its use in BM samples. Figure 1 Figure 1. Disclosures Kern: MLL Munich Leukemia Laboratory: Other: Part ownership.

Published
2021

32. Clinical application of flow cytometry in patients with unexplained cytopenia and suspected myelodysplastic syndrome: A report of the European <scp>LeukemiaNet</scp> International <scp>MDS‐Flow</scp> Cytometry Working Group

Author

Arjan A. van de Loosdrecht, Wolfgang Kern, Anna Porwit, Peter Valent, Sharham Kordasti, Eline Cremers, Canan Alhan, Carolien Duetz, Alan Dunlop, Willemijn Hobo, Frank Preijers, Orianne Wagner‐Ballon, Nicolas Chapuis, Michaela Fontenay, Peter Bettelheim, Lisa Eidenschink‐Brodersen, Patricia Font, Ulrika Johansson, Michael R. Loken, Jeroen G. te Marvelde, Sergio Matarraz, Kiyoyuki Ogata, Uta Oelschlaegel, Alberto Orfao, Katherina Psarra, Dolores Subirá, Denise A. Wells, Marie C. Béné, Matteo G. Della Porta, Kate Burbury, Frauke Bellos, Vincent H. J. van der Velden, Theresia M. Westers, Leonie Saft, and Robin Ireland

Subjects
Histology, Cell Biology, Pathology and Forensic Medicine
Published
2021

33. PBX1-directed stem cell transcriptional program drives tumor progression in myeloproliferative neoplasm

Author

Federico Colombo, Marta Ubezio, Emanuela Morenghi, Laura Crisafulli, Sharon Muggeo, Paolo Vezzoni, Clelia Peano, Elena Fontana, Anna Villa, Matteo G. Della Porta, Francesca Ficara, Rosita Rigoni, and Paolo Uva

Subjects
Myeloid, myeloproliferative neoplasm, MPN, Mice, Transgenic, Biology, Biochemistry, Transcriptome, CD61, Neoplasms, Report, Emb, hemic and lymphatic diseases, erythrocytosis, Genetics, medicine, Animals, Humans, RNA-Seq, JAK2V617F, Progenitor cell, Myeloproliferative neoplasm, Mice, Knockout, Myeloproliferative Disorders, Pbx1, Gene Expression Profiling, Pre-B-Cell Leukemia Transcription Factor 1, fungi, food and beverages, Granulocytosis, differentiation, Cell Biology, Hematopoietic Stem Cells, medicine.disease, Gene Expression Regulation, Neoplastic, Disease Models, Animal, Haematopoiesis, medicine.anatomical_structure, HSPC, Tumor progression, Mutation, Disease Progression, Cancer research, Stem cell, Signal Transduction, Developmental Biology
Abstract

Summary PBX1 regulates the balance between self-renewal and differentiation of hematopoietic stem cells and maintains proto-oncogenic transcriptional pathways in early progenitors. Its increased expression was found in myeloproliferative neoplasm (MPN) patients bearing the JAK2V617F mutation. To investigate if PBX1 contributes to MPN, and to explore its potential as therapeutic target, we generated the JP mouse strain, in which the human JAK2 mutation is induced in the absence of PBX1. Typical MPN features, such as thrombocythemia and granulocytosis, did not develop without PBX1, while erythrocytosis, initially displayed by JP mice, gradually resolved over time; splenic myeloid metaplasia and in vitro cytokine independent growth were absent upon PBX1 inactivation. The aberrant transcriptome in stem/progenitor cells from the MPN model was reverted by the absence of PBX1, demonstrating that PBX1 controls part of the molecular pathways deregulated by the JAK2V617F mutation. Modulation of the PBX1-driven transcriptional program might represent a novel therapeutic approach., Graphical abstract, Highlights • In the novel JP mouse, the JAK2V617F MPN-driver mutation is induced without Pbx1 • In JP mice, typical MPN features did not develop or resolved over time • The stem cell gene Pbx1 is a key contributor in establishing and maintaining MPN • Pbx1-dependent pathways may represent novel therapeutic targets for MPN, Ficara and colleagues generated a mouse model in which the human JAK2V617F myeloproliferative neoplasm (MPN) driver mutation is induced in the absence of the transcription factor Pbx1. Typical disease features did not develop or resolved over time, demonstrating that Pbx1 is a key contributor in establishing and maintaining MPN. Pbx1-dependent genes and pathways may represent novel therapeutic targets.

Published
2021

34. Prediction of thrombosis in post-polycythemia vera and post-essential thrombocythemia myelofibrosis: a study on 1258 patients

Author

Barbara Mora, Paola Guglielmelli, Andrew Kuykendall, Elisa Rumi, Margherita Maffioli, Francesca Palandri, Valerio De Stefano, Marianna Caramella, Silvia Salmoiraghi, Jean-Jacques Kiladjian, Jason Gotlib, Alessandra Iurlo, Francisco Cervantes, Marco Ruggeri, Richard T. Silver, Francesco Albano, Giulia Benevolo, David M. Ross, Matteo G. Della Porta, Timothy Devos, Giada Rotunno, Rami S. Komrokji, Ilaria C. Casetti, Michele Merli, Marco Brociner, Domenica Caramazza, Giuseppe Auteri, Tiziano Barbui, Daniele Cattaneo, Lorenza Bertù, Luca Arcaini, Alessandro M. Vannucchi, and Francesco Passamonti

Subjects
Cancer Research, Oncology, Primary Myelofibrosis, Humans, Hydroxyurea, Janus Kinase Inhibitors, Thrombosis, Hematology, Polycythemia Vera, Settore MED/15 - Malattie del Sangue, Thrombocythemia, Essential
Abstract

Patients with Philadelphia-negative myeloproliferative neoplasms are at high risk of thrombotic events (TEs). Predisposing factors have been identified in essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (primary MF, PMF), while yet not recognized in post PV/ET-MF (known as secondary MF, SMF). Within the 1258 SMF of the MYSEC (MYelofibrosis SECondary to PV and ET) dataset, 135 (10.7%) developed a TE at a median follow-up of 3.5 years (range, 1-21.4), with an incidence of 2.3% patients per year. Venous events accounted for two-thirds of the total. Cox multivariable analysis, supported by Fine-Gray models with death as competitive risk, showed that being on cytoreductive therapy at time of SMF evolution is associated with an absolute risk reduction of thrombosis equal to 3.3% within 3 years. Considering individually cytoreductive therapies, univariate regression model found that both conventional cytoreduction, mainly hydroxyurea, (HR 0.41, 95% CI: 0.26-0.65, p = 0.0001) and JAK inhibitors, mostly ruxolitinib, (HR 0.50, 95% CI: 0.24-1.02, p = 0.05) were associated with fewer thrombosis. Our study informs treating physicians of a non-low incidence of TEs in post PV/ET-MF and of the potential protective role of cytoreductive therapy in terms of thrombotic events.

Published
2022

35. An agenda to advance research in MDS: A TOP 10 Priority List from the first international workshop in MDS (iwMDS)

Author

Maximilian Stahl, Omar Abdel-Wahab, Andrew H. Wei, Michael R Savona, Mina L Xu, Zhuoer Xie, Justin Taylor, Daniel T Starczynowski, Guillermo F. Sanz, David A. Sallman, Valeria Santini, Gail J. Roboz, Mrinal M. Patnaik, Eric Padron, Olatoyosi Odenike, Aziz Nazha, Stephen D Nimer, Ravindra Majeti, Richard F Little, Steven D Gore, Alan F. List, Vijay Kuchroo, Rami S. Komrokji, Tae Kon Kim, Nina Kim, Christopher S Hourigan, Robert P Hasserjian, Stephanie Halene, Elizabeth A Griffiths, Peter L. Greenberg, Maria E. Figueroa, Pierre Fenaux, Fabio Efficace, Amy E. DeZern, Matteo G Della Porta, Naval G. Daver, Jane E. Churpek, Hetty E Carraway, Andrew M. Brunner, Uma Borate, John M Bennett, Rafael Bejar, Jacqueline Boultwood, Sanam Loghavi, Jan Philipp Bewersdorf, Uwe Platzbecker, David P. Steensma, Mikkael A. Sekeres, Rena J. Buckstein, and Amer M. Zeidan

Subjects
Hematology
Published
2022

36. Use of steroids in the management of low-risk myelodysplastic syndromes with autoimmune features

Author

Bruno, Fattizzo, Fabio, Serpenti, Francesco, Versino, Giulio, Cassanello, Lilla M, Cro, Marzia, Barbieri, Giorgio A, Croci, Nicoletta, Revelli, Matteo G, Della Porta, and Wilma, Barcellini

Abstract

The boundaries between myelodysplastic syndromes (MDS) and immune-mediated cytopenias are often difficult to establish and both conditions may benefit from immunosuppressive therapy. The optimal timing and doses of immunosuppressants are largely unknown.We systematically evaluated a retrospective cohort of 79 patients with low-risk MDS tested for anti-erythrocyte or anti-platelet autoantibodies to assess their frequency and the efficacy of immunosuppression, particularly with steroids.We found autoantibody positivity in 43% of cases and overt autoimmune diseases in 18%, including autoimmune hemolytic anemia, immune thromboctyopenia, and Evans syndrome. Steroid treatment improved cytopenia in about half of patients, with 26% achieving a complete recovery lasting for a median of 12 months. Better responses were observed in anemic patients with anti-erythrocyte autoantibodies than in those with anti-platelet autoantibodies, and the combination with recombinant erythropoietin (7/10) had a possible synergistic effect. Steroid doses were heterogeneous depending on the clinical intent (i.e., anti-inflammatory, immunosuppressive, anabolizing). Patients treated with a dose of 1 mg/kg day of prednisone for overt autoimmune cytopenia showed high rates of complete responses (60%).This observation suggests a trial with a short course (2-3 weeks) of standard steroid doses to ascertain efficacy and properly silence the autoimmune pathogenic mechanism. Steroid-related adverse events (16% of cases) should be monitored carefully in this elderly, frail population. In conclusion, features of autoimmunity are present in more than two-thirds of low-risk MDS patients and a trial with prednisone 0.5-1 mg/kg day for 2-3 weeks, with proper monitoring of adverse events, may be useful to improve cytopenias in selected cases.

Published
2022

37. Mutational profile of ZBTB16‐RARA‐positive acute myeloid leukemia

Author

Giulia Falconi, Ombretta Annibali, Roberto Castelli, Adriano Venditti, Antonio Cristiano, Matteo G. Della Porta, Anna Maria Testi, Eduardo Magalhães Rego, Laura Cicconi, Anna Maria Nardozza, Maria Teresa Voso, William Arcese, Pau Montesinos, Tiziana Ottone, Vladimir Lazarevic, Mariadomenica Divona, Francesco Lo-Coco, Jordi Esteve, Emiliano Fabiani, and Marianna Rossi

Subjects
Male, 0301 basic medicine, Cancer Research, Myeloid, Oncogene Proteins, Fusion, ARID1A, ZBTB16&#8208, Translocation, Genetic, Fusion gene, 0302 clinical medicine, Arsenic Trioxide, Leukemia, Promyelocytic, Acute, AML, Bone Marrow, hemic and lymphatic diseases, ZBTB16‐RARA, Promyelocytic Leukemia Zinc Finger Protein, Child, RC254-282, Original Research, RARA, Aged, 80 and over, Retinoic Acid Receptor alpha, High-Throughput Nucleotide Sequencing, Nuclear Proteins, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Myeloid leukemia, Middle Aged, Prognosis, DNA-Binding Proteins, Chromosome 17 (human), Leukemia, Myeloid, Acute, medicine.anatomical_structure, Oncology, NGS, 030220 oncology & carcinogenesis, SMARCA4, Female, Adult, Acute promyelocytic leukemia, Antineoplastic Agents, Tretinoin, Biology, 03 medical and health sciences, medicine, Humans, Radiology, Nuclear Medicine and imaging, neoplasms, Aged, ZBTB16-RARA, Chromosomes, Human, Pair 11, DNA Helicases, Clinical Cancer Research, Disseminated Intravascular Coagulation, Settore MED/15, medicine.disease, Retinoic acid receptor, 030104 developmental biology, Cancer research, Chromosomes, Human, Pair 17, Transcription Factors
Abstract

Background The ZBTB16‐RARA fusion gene, resulting from the reciprocal translocation between ZBTB16 on chromosome 11 and RARA genes on chromosome 17 [t(11;17)(q23;q21)], is rarely observed in acute myeloid leukemia (AML), and accounts for about 1% of retinoic acid receptor‐α (RARA) rearrangements. AML with this rare translocation shows unusual bone marrow (BM) morphology, with intermediate aspects between acute promyelocytic leukemia (APL) and AML with maturation. Patients may have a high incidence of disseminated intravascular coagulation at diagnosis, are poorly responsive to all‐trans retinoic acid (ATRA) and arsenic tryoxyde, and are reported to have an overall poor prognosis. Aims The mutational profile of ZBTB16‐RARA rearranged AML has not been described so far. Materials and methods We performed targeted next‐generation sequencing of 24 myeloid genes in BM diagnostic samples from seven ZBTB16‐RARA+AML, 103 non‐RARA rearranged AML, and 46 APL. The seven ZBTB16‐RARA‐positive patients were then screened for additional mutations using whole exome sequencing (n = 3) or an extended cancer panel including 409 genes (n = 4). Results ZBTB16‐RARA+AML showed an intermediate number of mutations per patient and involvement of different genes, as compared to APL and other AMLs. In particular, we found a high incidence of ARID1A mutations in ZBTB16‐RARA+AML (five of seven cases, 71%). Mutations in ARID2 and SMARCA4, other tumor suppressor genes also belonging to SWI/SNF chromatin remodeling complexes, were also identified in one case (14%). Discussion and conclusion Our data suggest the association of mutations of the ARID1A gene and of the other members of the SWI/SNF chromatin remodeling complexes with ZBTB16‐RARA+AMLs, where they may support the peculiar disease phenotype., This is the first report showing the mutational landscape of the rare ZBTB16‐RARA rearranged acute myeloid leukemia (AML). We identified a high frequency of ARID1A mutations, suggesting the involvement of the SWI/SNF chromatin remodeling complexes in the clinical presentation, acute promyelocytic leukemia‐like morphology and all‐trans retinoic acid/arsenic trioxide treatment resistance of ZBTB16‐RARA rearranged AMLs.

Published
2021

38. Daratumumab in transfusion-dependent patients with low or intermediate-1 risk myelodysplastic syndromes

Author

Agostino Cortelezzi, Ivo Nnane, Guillermo Garcia-Manero, Mariëlle Beckers, Vadim A Doronin, Brayan Merchan, María Díez-Campelo, Helen Varsos, Nikki A. Deangelis, Matteo G. Della Porta, Koen Van Eygen, Liang Xiu, Dimitri Breems, Esther Rose, Edo Vellenga, Valle Gomez, Meagan A. Jacoby, Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Stem Cell Aging Leukemia and Lymphoma (SALL)

Subjects
medicine.medical_specialty, business.industry, Internal medicine, Myelodysplastic syndromes, Transfusion dependence, MEDLINE, Medicine, Daratumumab, Hematology, business, medicine.disease
Published
2021

39. Pretransplant active disease status and HLA class II mismatching are associated with increased incidence and severity of cytokine release syndrome after haploidentical transplantation with posttransplant cyclophosphamide

Author

Clara Di Vito, Lucio Morabito, Carmelo Carlo-Stella, Armando Santoro, Matteo G. Della Porta, Stefania Bramanti, Chiara De Philippis, Jacopo Mariotti, Luca Castagna, Domenico Mavilio, Daniela Taurino, Fabrizio Marino, and Barbara Sarina

Subjects
0301 basic medicine, Male, Cancer Research, HLA mismatch, Transplantation Conditioning, Graft vs Host Disease, Kaplan-Meier Estimate, Gastroenterology, Severity of Illness Index, disease burden, 0302 clinical medicine, Risk Factors, Cumulative incidence, Bone Marrow Transplantation, Original Research, Univariate analysis, Incidence (epidemiology), Histocompatibility Testing, Incidence, Hazard ratio, haploidentical stem cell transplant with posttransplant cyclophosphamide, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Cytokine release syndrome, Oncology, 030220 oncology & carcinogenesis, Hematologic Neoplasms, Female, Immunosuppressive Agents, medicine.drug, Adult, medicine.medical_specialty, Cyclophosphamide, Side effect, Adolescent, Risk Assessment, lcsh:RC254-282, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Aged, Retrospective Studies, Peripheral Blood Stem Cell Transplantation, business.industry, Clinical Cancer Research, cytokine release syndrome, medicine.disease, Transplantation, 030104 developmental biology, Transplantation, Haploidentical, business, HLA-DRB1 Chains
Abstract

Cytokine release syndrome (CRS) represents a life‐threatening side effect after haploidentical stem cell transplantation (Haplo‐SCT) with posttransplant cyclophosphamide (PT‐Cy). Factors predictive of CRS development is still a matter of debate. We retrospectively analyzed 102 consecutive patients receiving a bone marrow (BM) (n = 42) or peripheral blood stem cells (PBSC) (n = 60) Haplo‐SCT with PT‐Cy. The two cohorts were similar in main patients’ characteristics besides disease type (P = .02). Cumulative incidence of grades 1, 2, and ≥3 CRS was 80%, 52%, and 15% at a median of 2, 4, and 7 days, respectively. Moderate/High‐grade fever (39°‐41°), grade 1 and grade ≥3 CRS occurred more frequently after PBSC relative to BM grafts (68% vs 33%, P = .0005; 87% vs 71%, P = .009; 20% vs 7%, P = .07). Only patients experiencing grade ≥3 CRS had a worse outcome in terms of 1‐year overall survival (OS) and nonrelapse mortality (NRM): 39% vs 80% (P = .002) and 40% vs 8% (P = .005), respectively. By univariate analysis the only factors associated with the increased risk of ≥3 CRS were pretransplant disease status (8% for complete remission, 11% for partial remission, and 38% for active disease, P = .002), HLA‐DRB1 mismatching (57% vs 14%, P = .007), and PBSC graft (P = .07). By multivariable analysis, only pretransplant disease status (hazard ratio, HR: 6.84, P = .005) and HLA‐DRB1 mismatching (HR: 17.19, P = .003) remained independent predictors of grade ≥3 CRS. Only grade ≥3 CRS is clinically relevant for the final outcome of patients receiving Haplo‐SCT with PT‐Cy, is more frequent after a PBSC graft and is associated with pretransplant active disease and HLA‐DRB1 mismatching., Severe cytokine release syndrome (CRS) may occur after T‐cell‐replete haploidentical stem cell transplantation and conditions nonrelapse mortality. Disease burden and HLA mismatch in the graft‐vs‐host‐disease direction are the main factors affecting the occurrence of severe CRS.

Published
2020

40. A prognostic model for patients with lymphoma and COVID-19: a multicentre cohort study

Author

Francesco Merli, Carlo Visco, Annarita Conconi, Daniele Vallisa, Elettra Ortu La Barbera, Sara Galimberti, Roberto Mina, Marianna Sassone, Anna Guidetti, Adriano Venditti, Alessandro Corso, Francesco Marchesi, Pellegrino Musto, Agostino Tafuri, Valentina Bonuomo, Filippo Gherlinzoni, Francesco Lanza, Monia Marchetti, Safaa M. Ramadan, Marco Salvini, Massimo Massaia, Elisa Coviello, Alessandro Busca, Luigi Petrucci, Daniele Armiento, Mauro Turrini, Alessandra Romano, Chiara Cattaneo, Francesco Passamonti, Matteo G. Della Porta, Anna Candoni, Luigi Rigacci, Luca Arcaini, Livio Trentin, Valeria Cardinali, Maria Chiara Tisi, Carmine Selleri, Carlo Gambacorti-Passerini, Andrés J.M. Ferreri, Patrizia Tosi, Riccardo Bruna, Mauro Krampera, Antonio Cuneo, Nicola Stefano Fracchiolla, Daniela Cilloni, Lorenza Bertù, Paolo Corradini, Annamaria Scattolin, Roberto Cairoli, Giuseppe Visani, Domenico Penna, Marco Ladetto, Antonello Pinto, Michele Cavo, Monica Bocchia, Sofia Pilerci, Luigi Marcheselli, Visco, C, Marcheselli, L, Mina, R, Sassone, M, Guidetti, A, Penna, D, Cattaneo, C, Bonuomo, V, Busca, A, Ferreri, A, Bruna, R, Petrucci, L, Cairoli, R, Salvini, M, Bertu, L, Ladetto, M, Pilerci, S, Pinto, A, Ramadan, S, Marchesi, F, Cavo, M, Arcaini, L, Coviello, E, Romano, A, Musto, P, Massaia, M, Fracchiolla, N, Marchetti, M, Scattolin, A, Tisi, M, Cuneo, A, Porta, M, Trentin, L, Turrini, M, Gherlinzoni, F, Tafuri, A, Galimberti, S, Bocchia, M, Cardinali, V, Cilloni, D, Corso, A, Armiento, D, Rigacci, L, La Barbera, E, Gambacorti Passerini, C, Visani, G, Vallisa, D, Venditti, A, Selleri, C, Conconi, A, Tosi, P, Lanza, F, Candoni, A, Krampera, M, Corradini, P, Passamonti, F, and Merli, F

Subjects
Adult, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Aged, Aged, 80 and over, Cohort Studies, Humans, Middle Aged, Prognosis, SARS-CoV-2, Young Adult, COVID-19, Lymphoma, Lymphocyte, medicine.medical_treatment, Disease, NO, lymphoma, COVID-19, multicentre cohort study, SARS-CoV-2, Internal medicine, medicine, 80 and over, lymphoma, covid-19, anti-cd20, business.industry, Regular Article, Immunosuppression, Hematology, Settore MED/15, medicine.disease, medicine.anatomical_structure, Cohort, Prognostic model, business, Cohort study
Abstract

Lymphoma represents a heterogeneous hematological malignancy (HM), which is characterized by severe immunosuppression. Patients diagnosed of coronavirus disease 2019 (COVID-19) during the course of HM have been described to have poor outcome, with only few reports specifically addressing lymphoma patients. Here, we investigated the clinical behavior and clinical parameters of a large multicenter cohort of adult patients with different lymphoma subtypes, with the aim of identifying predictors of death. The study included 856 patients, of whom 619 were enrolled prospectively in a 1-year frame and were followed-up for a median of 66 days (range 1-395). Patients were managed as outpatient (not-admitted cohort, n = 388) or required hospitalization (n = 468), and median age was 63 years (range 19-94). Overall, the 30- and 100-days mortality was 13% (95% confidence interval (CI), 11% to 15%) and 23% (95% CI, 20% to 27%), respectively. Antilymphoma treatment, including anti-CD20 containing regimens, did not impact survival. Patients with Hodgkin’s lymphoma had the more favorable survival, but this was partly related to significantly younger age. The time interval between lymphoma diagnosis and COVID-19 was inversely related to mortality. Multivariable analysis recognized 4 easy-to-use factors (age, gender, lymphocyte, and platelet count) that were associated with risk of death, both in the admitted and in the not-admitted cohort (HR 3.79 and 8.85 for the intermediate- and high-risk group, respectively). Overall, our study shows that patients should not be deprived of the best available treatment of their underlying disease and indicates which patients are at higher risk of death. This study was registered with ClinicalTrials.gov, NCT04352556.

Published
2022

41. Incidence, Clinical Associations, and Co-Mutation Patterns of UBA1 Mutations in MDS

Author

Maria Sirenko, Elsa Bernard, David B. Beck, Maria Creignou, Dylan Domenico, Andrea Farina, Juan E Arango, Olivier Kosmider, Robert P. Hasserjian, Martin Jadersten, Ulrich Germing, Guillermo Sanz, Arjan A. van de Loosdrecht, Matilde Y Follo, Felicitas R. Thol, Lurdes Zamora, Ronald Feitosa Pinheiro, Andrea Pellagatti, Harold K. Elias, Detlef Haase, Christina Ganster, Lionel Ades, Magnus Tobiasson, Laura Palomo, Matteo G. Della Porta, Kety Huberman, Pierre Fenaux, Monika Belickova, Michael R. Savona, Virginia M. Klimek, Fabio Pires de Souza Santos, Jacqueline Boultwood, Ioannis Kotsianidis, Valeria Santini, Francesc Solé, Uwe Platzbecker, Michael Heuser, Peter Valent, Carlo Finelli, Maria Teresa Voso, Lee-Yung Shih, Seishi Ogawa, Michaela Fontenay, Joop H. Jansen, Jose Cervera, Benjamin L. Ebert, Rafael Bejar, Peter L Greenberg, Norbert Gattermann, Luca Malcovati, Mario Cazzola, Eva Hellström-Lindberg, and Elli Papaemmanuil

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

42. Prognostic impact of somatic mutations on time to first treatment: Results of targeted next-generation sequencing in 211 patients with early stage chronic lymphocytic leukemia

Author

Chiara Cavalloni, Massimo Gentile, Fabio Bergamini, Silvia Zibellini, Matteo G. Della Porta, Anna Gallì, Luca Arcaini, Marzia Varettoni, Sara Rattotti, Ettore Rizzo, Elena Flospergher, Ester Orlandi, Caterina Cristinelli, Nicole Fabbri, Marianna Rossi, and Virginia Valeria Ferretti

Subjects
Oncology, medicine.medical_specialty, Somatic cell, business.industry, Time to first treatment, Chronic lymphocytic leukemia, High-Throughput Nucleotide Sequencing, Hematology, medicine.disease, Prognosis, Leukemia, Lymphocytic, Chronic, B-Cell, DNA sequencing, Cohort Studies, Internal medicine, Mutation, medicine, Humans, Stage (cooking), business
Published
2021

43. Thiotepa, Fludarabine, and Busulfan Conditioning Regimen before T Cell–Replete Haploidentical Transplantation with Post-Transplant Cyclophosphamide for Acute Myeloid Leukemia: A Bicentric Experience of 100 Patients

Author

Matteo G. Della Porta, Raynier Devillier, Angela Granata, Claude Lemarie, Boris Calmels, Samia Harbi, Lucas Castagna, Thomas Pagliardini, Colombe Saillard, Sabine Furst, Pierre-Jean Weiller, Catherine Faucher, Djamel Mokart, Faezeh Legrand, Christian Chabannon, Stefania Bramanti, Didier Blaise, Wang Lining, Norbert Vey, Valerio Maisano, Aude Charbonnier, and Jerome Rey

Subjects
Adult, Male, Oncology, medicine.medical_specialty, Transplantation Conditioning, Cyclophosphamide, T-Lymphocytes, Graft vs Host Disease, Disease, ThioTEPA, Disease-Free Survival, hemic and lymphatic diseases, Internal medicine, Humans, Medicine, Busulfan, Aged, Transplantation, business.industry, Incidence (epidemiology), Myeloid leukemia, Hematology, Middle Aged, Allografts, Fludarabine, Survival Rate, Leukemia, Myeloid, Acute, surgical procedures, operative, Chronic Disease, Female, business, Thiotepa, Vidarabine, Stem Cell Transplantation, medicine.drug
Abstract

Haploidentical stem cell transplantation (haplo-SCT) with post-transplant cyclophosphamide (PT-Cy) is an alternative treatment for acute myeloid leukemia (AML) patients who lack HLA-matched donors. Relapse after haplo-SCT remains a major concern, especially after nonmyeloablative conditioning regimens. Promising results were reported for TBF-based conditioning regimens (thiotepa, busulfan, and fludarabine) in patients transplanted from different categories of donors and for various disease types but not specifically in PT-Cy haplo-SCT for AML. Here we evaluate the outcome of 100 AML patients who received haplo-SCT with PT-Cy after TBF conditioning regimens (reduced-intensity conditioning, n = 77; myeloablative conditioning, n = 23) in 2 transplant programs. Cumulative incidences of grades III to IV acute and moderate or severe chronic graft-versus-host disease (GVHD) were 7% and 14%, respectively. NRM at 2 years was 28%, significantly influenced by disease status at haplo-SCT (first complete response [CR1] versus advanced AML: 16% versus 38%, P = .016) but not by conditioning intensity or age. The cumulative incidences of relapse at 2 years were 17% and 24% in CR1 and advanced AML, respectively (not significant). Progression-free survival, overall survival, and GVHD and relapse-free survival at 2 years were 67%, 71%, and 49% in CR1 patients, respectively, whereas comparative values in patients with advanced disease were 37%, 41%, and 32%. Our study suggests that TBF conditioning for PT-Cy haplo-SCT is safe and effective for AML patients in CR1. In patients with more advanced disease, the relatively low incidence of relapse seems counterbalanced by a high nonrelapse mortality, underlining the need for alternative strategies to decrease relapse risk, without increasing the intensity of conditioning regimen.

Published
2019

44. Classification and Personalized Prognostic Assessment on the Basis of Clinical and Genomic Features in Myelodysplastic Syndromes

Author

Andrea Bacigalupo, Pierre Fenaux, Alberto Termanini, Marianna Rossi, Lucio Morabito, Niccolo Bolli, Massimo Bernardi, Victor Savevski, Manja Meggendorfer, Daniel Remondini, Tommaso Matteuzzi, Torsten Haferlach, Luciano Milanesi, Matteo G. Della Porta, Ettore Mosca, Gastone Castellani, Valeria Santini, Alessandro Rambaldi, Giulia Maggioni, Guillermo Sanz, Claudia Sala, Wolfgang Kern, Marta Ubezio, Matteo Zampini, Emanuele Angelucci, Armando Santoro, Laura Palomo, Noemi Di Nanni, Lorenza Borin, Erica Travaglino, Alessia Campagna, Maria Teresa Voso, Francesc Solé, Francesca Bonifazi, Shahram Kordasti, Uwe Platzbecker, Matteo Bersanelli, Matteo Gnocchi, Esther Oliva, Marta Riva, Benedetto Bruno, Fabio Ciceri, Francesco Passamonti, Claudia Saitta, Enrico Giampieri, Chiara Chiereghin, Bersanelli, Matteo, Travaglino, Erica, Meggendorfer, Manja, Matteuzzi, Tommaso, Sala, Claudia, Mosca, Ettore, Chiereghin, Chiara, Di Nanni, Noemi, Gnocchi, Matteo, Zampini, Matteo, Rossi, Marianna, Maggioni, Giulia, Termanini, Alberto, Angelucci, Emanuele, Bernardi, Massimo, Borin, Lorenza, Bruno, Benedetto, Bonifazi, Francesca, Santini, Valeria, Bacigalupo, Andrea, Voso, Maria Teresa, Oliva, Esther, Riva, Marta, Ubezio, Marta, Morabito, Lucio, Campagna, Alessia, Saitta, Claudia, Savevski, Victor, Giampieri, Enrico, Remondini, Daniel, Passamonti, Francesco, Ciceri, Fabio, Bolli, Niccolò, Rambaldi, Alessandro, Kern, Wolfgang, Kordasti, Shahram, Sole, Francesc, Palomo, Laura, Sanz, Guillermo, Santoro, Armando, Platzbecker, Uwe, Fenaux, Pierre, Milanesi, Luciano, Haferlach, Torsten, Castellani, Gastone, and Della Porta, Matteo G

Subjects
Male, Cancer Research, SCORING SYSTEM, MODELS, disease classification, MEDLINE, ACUTE MYELOID-LEUKEMIA, Computational biology, 03 medical and health sciences, 0302 clinical medicine, Text mining, hemic and lymphatic diseases, MDS, medicine, CRITERIA, Humans, NGS, somatic mutations, myelodysplastic syndromes, prognosis, 030304 developmental biology, Retrospective Studies, 0303 health sciences, GENETIC LESIONS, business.industry, Myelodysplastic syndromes, Disease classification, Retrospective cohort study, SOMATIC MUTATIONS, Genomics, MDS, Artificial Intekkìlligence, machine learning, Settore MED/15, medicine.disease, Prognosis, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Myelodysplastic Syndromes, Female, prognostication, business
Abstract

PURPOSE Recurrently mutated genes and chromosomal abnormalities have been identified in myelodysplastic syndromes (MDS). We aim to integrate these genomic features into disease classification and prognostication. METHODS We retrospectively enrolled 2,043 patients. Using Bayesian networks and Dirichlet processes, we combined mutations in 47 genes with cytogenetic abnormalities to identify genetic associations and subgroups. Random-effects Cox proportional hazards multistate modeling was used for developing prognostic models. An independent validation on 318 cases was performed. RESULTS We identify eight MDS groups (clusters) according to specific genomic features. In five groups, dominant genomic features include splicing gene mutations ( SF3B1, SRSF2, and U2AF1) that occur early in disease history, determine specific phenotypes, and drive disease evolution. These groups display different prognosis (groups with SF3B1 mutations being associated with better survival). Specific co-mutation patterns account for clinical heterogeneity within SF3B1- and SRSF2-related MDS. MDS with complex karyotype and/or TP53 gene abnormalities and MDS with acute leukemia–like mutations show poorest prognosis. MDS with 5q deletion are clustered into two distinct groups according to the number of mutated genes and/or presence of TP53 mutations. By integrating 63 clinical and genomic variables, we define a novel prognostic model that generates personally tailored predictions of survival. The predicted and observed outcomes correlate well in internal cross-validation and in an independent external cohort. This model substantially improves predictive accuracy of currently available prognostic tools. We have created a Web portal that allows outcome predictions to be generated for user-defined constellations of genomic and clinical features. CONCLUSION Genomic landscape in MDS reveals distinct subgroups associated with specific clinical features and discrete patterns of evolution, providing a proof of concept for next-generation disease classification and prognosis.

Published
2021

45. Bortezomib-based therapy in non-transplant multiple myeloma patients: a retrospective cohort study from the FABIO project

Author

Salvatore Scondotto, Mirko Di Martino, Marilena Romero, Donatella Garau, Ilenia De Carlo, Claudia Vener, Matteo Franchi, Matteo G. Della Porta, Giovanni Corrao, Francesco Passamonti, Ursula Kirchmayer, Chiara Stival, Franchi, M, Vener, C, Garau, D, Kirchmayer, U, Di Martino, M, Romero, M, De Carlo, I, Scondotto, S, Stival, C, Della Porta, M, Passamonti, F, and Corrao, G

Subjects
Oncology, medicine.medical_specialty, real-world, Cost effectiveness, cost-effectivene, effectiveness, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Medicine, 030212 general & internal medicine, cost-effectiveness, Multiple myeloma, Original Research, lcsh:RC633-647.5, business.industry, Bortezomib, Disease progression, bortezomib, multiple myeloma, Retrospective cohort study, lcsh:Diseases of the blood and blood-forming organs, Hematology, medicine.disease, 030220 oncology & carcinogenesis, Conventional chemotherapy, business, effectivene, medicine.drug
Abstract

Introduction: Randomized clinical trials showed that bortezomib, in addition to conventional chemotherapy, improves survival and disease progression in multiple myeloma (MM) patients not eligible for stem cell transplantation. The aim of this retrospective population-based cohort study is the evaluation of both clinical and economic profile of bortezomib-based versus conventional chemotherapy in daily clinical practice. Methods: Healthcare utilization databases of six Italian regions were used to identify adult patients with non-transplant MM, who started a first-line therapy with bortezomib-based or conventional chemotherapy. Patients were matched by propensity score and were followed from treatment start until death, lost to follow-up or study end-point. Overall survival (OS) and restricted mean survival time (RMST) were estimated using the Kaplan–Meier method. Association between first-line treatment and risk of death was estimated by a conditional Cox proportional regression model. Average mean cumulative costs were estimated and compared between groups. Results: In the period 2010–2016, 3509 non-transplant MM patients met the inclusion criteria, of which 1157 treated with bortezomib-based therapy were matched to 1826 treated with conventional chemotherapy. Median OS and RMST were 33.9 and 27.9 months, and 42.9 and 38.4 months, respectively, in the two treatment arms. Overall, these values corresponded to a HR of death of 0.79 (95% CI 0.71–0.89) over a time horizon of 84 months. Average cumulative cost were 83,839 € and 54,499 €, respectively, corresponding to an incremental cost-effectiveness ratio of 54,333 € per year of life gained, a cost coherent with the willingness-to-pay thresholds frequently adopted from Western countries. Conclusions: These data suggested that, in a large cohort of non-transplant MM patients treated outside the experimental setting, first-line treatment with bortezomib-based therapy was associated with a favourable effectiveness and cost-effectiveness profile.

Published
2021

46. What changed in the Italian internal medicine and geriatric wards during the lockdown

Author

M. C. Nava, Ligia J. Dominguez, F. Giofre, S. Dassi, Stella Provini, Roberto Castello, Maria Elena Pipita, Raffaele Landolfi, I. Indiano, S. Schiavone, Renzo Rozzini, Matteo G. Della Porta, A. Cespiati, F. Perticone, G. Bartelloni, Miriam Gino, Maurizio Corsi, Lina Falanga, R. Di Quattro, G. Orio, Salvatore Piro, Antonio Mirijello, Alessio Molfino, L. Biondi, Leonardo A. Sechi, Luciano Ottonello, Marco Bertolotti, C. Sidoli, G. Colombo, C. Bussolino, A. Delitala, P. M. Mannucci, Luigina Guasti, Antonio Nouvenne, Marta Di Pasquale, P. Peasso, E. Favale, A. Volpini, Giulia Costanzo, C. Margaria, S. Morganti, Guido Moreo, F. Nasso, S. Dolenti, Enrico Strocchi, Laura Stefani, Cristian Petri, M. M. De Amicis, Maria Domenica Cappellini, E. Magnolfi, G. Principato, Fabio Fabbian, G. D'Aurizio, M. V. Libbra, Fabrizio Fabris, Michela Zanetti, P. Tarsitani, V. Piccinelli, R. Caruso, Andrea Artoni, G. Argiolas, A. D. Di Mauro, C. Custodero, Angela Sciacqua, Gabriella Gruden, Anna Ludovica Fracanzani, A. Falcetta, M. L. Matacena, E. Ianniello, G. Bogoni, M. Soldati, P. Agosti, Patrizia Mecocci, Benedetta Marigliano, Chiara Lonati, Luca Zanoli, Massimo Raspanti, F. Gandolfo, C. Catena, Paolo Rossi, Francesco Salerno, Carlotta Franchi, A. Gennaro, P. Bocchi, Elena Silvestri, R. Leonardi, Raffaella Rossio, M. Vanoli, V. Gioffre, L. Fondrieschi, B. D'Avanzo, N. Scaramellini, S. Del Giacco, A. da Porto, G. Serafini, I. Rossi, Giuseppe Palasciano, R. Gonella, Alice Valoriani, Antonella Afeltra, Filippo Alessandro Montalto, C. Antonucci, Giorgio Galanti, F. Montecucco, I. Aiello, Giuseppe Natoli, Antonio Brucato, C. Di Gennaro, Marco Zoli, Teresa Salvatore, Maria Ester Modeo, Mosè Bartone, Ilaria Ardoino, Flora Peyvandi, E. Simeone, Y. Grassi, Paolo Gallo, S. Leoni, S. Buffelli, Giacomo Emmi, Antonio Cittadini, Maria Teresa Guagnano, F. Corica, Giorgio Basile, G. Oberti, Giulia Grignani, G. Vannini, B. Graziella, A De Giorgi, Roberto Tarquini, G. M. De Vincenzo, M. Fogliati, G. Famularo, Antonio Picardi, Chiara Mussi, Andrea Maria Maresca, M. Pisati, Silvia Prolo, Domenico Girelli, Maurizio Muscaritoli, E. Amoruso, Silvia Ghidoni, Marco Vincenzo Lenti, Caterina Mengoli, Vanessa Bianconi, Carlo Vigorito, M. Galassi, A. Di Pino, M. Bellan, M. Girino, F. Bellone, V. Beccati, Luigi Anastasio, Laura Cortesi, M. Mattioli, Giuseppe Montalto, Gino Roberto Corazza, S. Fragapani, M. V. Rabuini, Pietro Minuz, Lara Caserza, R. Battaglia, F. Cacioppo, D. Cerminara, S. Di Marca, Gian Paolo Ceda, V. Beneduce, A. Ballestrero, Giuseppe Montrucchio, G. De Luca, G. P. Fra, Vincenzo Stanghellini, Raffaele Maio, A. Cavarape, N. Passariello, F. Berti, Patrizia Suppressa, Benedetta Stancanelli, A. Giorgi, Marta Rizzo, L. Colangelo, Massimo Montalto, A. Pilotto, Anna Licata, Francesco Violi, M. S. Pisciotta, Maria Perticone, Giuseppe Zuccalà, Virginia Boccardi, L. Ricevuti, Alessandra Marengoni, Giuseppe Romanelli, V. Saracco, Paola Riva, Giuseppe Paolisso, Alessandro Nobili, Francesco Saverio Vella, S. Tiraboschi, G. Pallini, G. Vischi, Nicola Lucio Liberato, R. Tiseo, Valter Monzani, Marcello Maggio, G. Damiani, G. Leoncini, M. Sanino, M. Cesari, Luana Castiglioni, G. Miglio, Luciano Rinaldi, M. Cilli, T. de Falco, C. Ricozzi, F. Tolloso, R. D. Diprizio, M. Berria, S. Mularo, A. Comitangelo, Carmelinda Ruggiero, Eugenio Ruggeri, Claudio Borghi, Tiziana Tognin, Antonino Catalano, A. Simili, Agostino Gaudio, Mario Barbagallo, Emanuela Miceli, Luca Pasina, A. Vignali, Alessandro Salvi, Giuseppe Delitala, Elena Succurro, Maria Antonietta Bleve, Alessio Novella, Sergio Harari, D. Sola, A. Dal Col, A. Di Sabatino, F. Ferrando, Enrico Petrillo, Francesco Baffa Bellucci, Andrea Ticinesi, L. La Malfa, Davide Firinu, Franco Arturi, Umberto Vespasiani Gentilucci, Lorenzo Malatino, Alessandra Bettiol, Valeria Savojardo, Francesca Mete, R. Quadri, Mancuso G, G. Pina, C. Poletto, G. Colussi, Sarah Damanti, Ginevra De Marchi, Graziana Lupattelli, Mario Pirisi, Pietro Castellino, A. Greco, Marta Clerici, Michela Novelli, Giulia Lancellotti, R. Volpi, R. Scurti, T. Prandini, Marco Carbone, E.A. Pulixi, Gianni Biolo, S. del Vecchio, W. Capeci, Tiziana Meschi, Luigi Fenoglio, Giovanna Fabio, R. Ghio, Francesco Cipollone, Leonardo Campiotti, G. P. Martino, Michela Pasino, Maria Grazia Serra, A. Bragagni, Roberto Pontremoli, Salvatore Corrao, Mauro Tettamanti, C. Catalano, L. Monaco, S. Berra, Alice Grossi, Giuseppe Bellelli, G. N. Imperiale, C. Principato, Gabriele Mascherini, E. Larovere, A. Pietrangelo, Giancarlo Labbadia, Fabiana Busti, I. Bertozzi, F. Napoli, Domenico Prisco, G. Nobili, Carlo Sabbà, Francesco Purrello, P. Pettinari, B. Tassone, G. Ceriani, G. Scanzi, S. Baldassarre, I. Mattioli, G. Sigon, Costanza Caccia Dominioni, Alessandro Squizzato, C. Gracin, Benedetta Boari, Roberto Manfredini, M. Grossi, Salvatore Minisola, Daniela Calipari, R. Alcidi, D. Lucente, V. Terranova, D'Avanzo B., Nobili A., Tettamanti M., Pasina L., Mannucci P.M., Pietrangelo A., Perticone F., Violi F., Corazza G.R., Corrao S., Marengoni A., Salerno F., Cesari M., Franchi C., Cortesi L., Miglio G., Ardoino I., Novella A., Prisco D., Silvestri E., Emmi G., Bettiol A., Mattioli I., Biolo G., Zanetti M., Bartelloni G., Vanoli M., Grignani G., Pulixi E.A., Lupattelli G., Bianconi V., Alcidi R., Girelli D., Busti F., Marchi G., Barbagallo M., Dominguez L., Beneduce V., Cacioppo F., Natoli G., Mularo S., Raspanti M., Zoli M., Matacena M.L., Orio G., Magnolfi E., Serafini G., Simili A., Palasciano G., Modeo M.E., Di Gennaro C., Cappellini M.D., Fabio G., de Amicis M.M., de Luca G., Scaramellini N., Rossi P.D., Damanti S., Clerici M., Leoni S., Di Mauro A.D., Di Sabatino A., Miceli E., Lenti M.V., Pisati M., Dominioni C.C., Pontremoli R., Beccati V., Nobili G., Leoncini G., Anastasio L., Carbone M., Cipollone F., Guagnano M.T., Rossi I., Mancuso G., Calipari D., Bartone M., Delitala G., Berria M., Delitala A., Muscaritoli M., Molfino A., Petrillo E., Giorgi A., Gracin C., Zuccala G., D'Aurizio G., Romanelli G., Volpini A., Lucente D., Picardi A., Gentilucci U.V., Gallo P., Bellelli G., Corsi M., Antonucci C., Sidoli C., Principato G., Arturi F., Succurro E., Tassone B., Giofre F., Serra M.G., Bleve M.A., Brucato A., de Falco T., Fabris F., Bertozzi I., Bogoni G., Rabuini M.V., Prandini T., Manfredini R., Fabbian F., Boari B., de Giorgi A., Tiseo R., Paolisso G., Rizzo M.R., Catalano C., Borghi C., Strocchi E., Ianniello E., Soldati M., Schiavone S., Bragagni A., Sabba C., Vella F.S., Suppressa P., de Vincenzo G.M., Comitangelo A., Amoruso E., Custodero C., Fenoglio L., Falcetta A., Fracanzani A.L., Tiraboschi S., Cespiati A., Oberti G., Sigon G., Peyvandi F., Rossio R., Colombo G., Agosti P., Monzani V., Savojardo V., Ceriani G., Pallini G., Montecucco F., Ottonello L., Caserza L., Vischi G., Liberato N.L., Tognin T., Purrello F., Di Pino A., Piro S., Rozzini R., Falanga L., Pisciotta M.S., Bellucci F.B., Buffelli S., Montrucchio G., Peasso P., Favale E., Poletto C., Margaria C., Sanino M., Guasti L., Castiglioni L., Maresca A., Squizzato A., Campiotti L., Grossi A., Diprizio R.D., Bertolotti M., Mussi C., Lancellotti G., Libbra M.V., Galassi M., Grassi Y., Greco A., Sciacqua A., Perticone M., Battaglia R., Maio R., Stanghellini V., Ruggeri E., del Vecchio S., Salvi A., Leonardi R., Damiani G., Capeci W., Mattioli M., Martino G.P., Biondi L., Pettinari P., Ghio R., Dal Col A., Minisola S., Colangelo L., Cilli M., Labbadia G., Afeltra A., Marigliano B., Pipita M.E., Castellino P., Zanoli L., Gennaro A., Gaudio A., Saracco V., Fogliati M., Bussolino C., Mete F., Gino M., Vigorito C., Cittadini A., Moreo G., Prolo S., Pina G., Ballestrero A., Ferrando F., Gonella R., Cerminara D., Berra S., Dassi S., Nava M.C., Graziella B., Baldassarre S., Fragapani S., Gruden G., Galanti G., Mascherini G., Petri C., Stefani L., Girino M., Piccinelli V., Nasso F., Gioffre V., Pasquale M., Sechi L., Catena C., Colussi G., Cavarape A., da Porto A., Passariello N., Rinaldi L., Berti F., Famularo G., Tarsitani P., Castello R., Pasino M., Ceda G.P., Maggio M.G., Morganti S., Artoni A., Grossi M., Del Giacco S., Firinu D., Costanzo G., Argiolas G., Montalto G., Licata A., Montalto F.A., Corica F., Basile G., Catalano A., Bellone F., Principato C., Malatino L., Stancanelli B., Terranova V., Di Marca S., Di Quattro R., la Malfa L., Caruso R., Mecocci P., Ruggiero C., Boccardi V., Meschi T., Ticinesi A., Nouvenne A., Minuz P., Fondrieschi L., Imperiale G.N., Pirisi M., Fra G.P., Sola D., Bellan M., Porta M., Riva P., Quadri R., Larovere E., Novelli M., Scanzi G., Mengoli C., Provini S., Ricevuti L., Simeone E., Scurti R., Tolloso F., Tarquini R., Valoriani A., Dolenti S., Vannini G., Volpi R., Bocchi P., Vignali A., Harari S., Lonati C., Napoli F., Aiello I., Landolfi R., Montalto M., Mirijello A., Ghidoni S., Salvatore T., Monaco L., Ricozzi C., Pilotto A., Indiano I., Gandolfo F., D'Avanzo, B, Nobili, A, Tettamanti, M, Pasina, L, Mannucci, P, Bellelli, G, D'Avanzo, B., Nobili, A., Tettamanti, M., Pasina, L., Mannucci, P. M., Pietrangelo, A., Perticone, F., Violi, F., Corazza, G. R., Corrao, S., Marengoni, A., Salerno, F., Cesari, M., Franchi, C., Cortesi, L., Miglio, G., Ardoino, I., Novella, A., Prisco, D., Silvestri, E., Emmi, G., Bettiol, A., Mattioli, I., Biolo, G., Zanetti, M., Bartelloni, G., Vanoli, M., Grignani, G., Pulixi, E. A., Lupattelli, G., Bianconi, V., Alcidi, R., Girelli, D., Busti, F., Marchi, G., Barbagallo, M., Dominguez, L., Beneduce, V., Cacioppo, F., Natoli, G., Mularo, S., Raspanti, M., Zoli, M., Matacena, M. L., Orio, G., Magnolfi, E., Serafini, G., Simili, A., Palasciano, G., Modeo, M. E., Di Gennaro, C., Cappellini, M. D., Fabio, G., de Amicis, M. M., de Luca, G., Scaramellini, N., Rossi, P. D., Damanti, S., Clerici, M., Leoni, S., Di Mauro, A. D., Di Sabatino, A., Miceli, E., Lenti, M. V., Pisati, M., Dominioni, C. C., Pontremoli, R., Beccati, V., Nobili, G., Leoncini, G., Anastasio, L., Carbone, M., Cipollone, F., Guagnano, M. T., Rossi, I., Mancuso, G., Calipari, D., Bartone, M., Delitala, G., Berria, M., Delitala, A., Muscaritoli, M., Molfino, A., Petrillo, E., Giorgi, A., Gracin, C., Zuccala, G., D'Aurizio, G., Romanelli, G., Volpini, A., Lucente, D., Picardi, A., Gentilucci, U. V., Gallo, P., Bellelli, G., Corsi, M., Antonucci, C., Sidoli, C., Principato, G., Arturi, F., Succurro, E., Tassone, B., Giofre, F., Serra, M. G., Bleve, M. A., Brucato, A., de Falco, T., Fabris, F., Bertozzi, I., Bogoni, G., Rabuini, M. V., Prandini, T., Manfredini, R., Fabbian, F., Boari, B., de Giorgi, A., Tiseo, R., Paolisso, G., Rizzo, M. R., Catalano, C., Borghi, C., Strocchi, E., Ianniello, E., Soldati, M., Schiavone, S., Bragagni, A., Sabba, C., Vella, F. S., Suppressa, P., de Vincenzo, G. M., Comitangelo, A., Amoruso, E., Custodero, C., Fenoglio, L., Falcetta, A., Fracanzani, A. L., Tiraboschi, S., Cespiati, A., Oberti, G., Sigon, G., Peyvandi, F., Rossio, R., Colombo, G., Agosti, P., Monzani, V., Savojardo, V., Ceriani, G., Pallini, G., Montecucco, F., Ottonello, L., Caserza, L., Vischi, G., Liberato, N. L., Tognin, T., Purrello, F., Di Pino, A., Piro, S., Rozzini, R., Falanga, L., Pisciotta, M. S., Bellucci, F. B., Buffelli, S., Montrucchio, G., Peasso, P., Favale, E., Poletto, C., Margaria, C., Sanino, M., Guasti, L., Castiglioni, L., Maresca, A., Squizzato, A., Campiotti, L., Grossi, A., Diprizio, R. D., Bertolotti, M., Mussi, C., Lancellotti, G., Libbra, M. V., Galassi, M., Grassi, Y., Greco, A., Sciacqua, A., Perticone, M., Battaglia, R., Maio, R., Stanghellini, V., Ruggeri, E., del Vecchio, S., Salvi, A., Leonardi, R., Damiani, G., Capeci, W., Mattioli, M., Martino, G. P., Biondi, L., Pettinari, P., Ghio, R., Dal Col, A., Minisola, S., Colangelo, L., Cilli, M., Labbadia, G., Afeltra, A., Marigliano, B., Pipita, M. E., Castellino, P., Zanoli, L., Gennaro, A., Gaudio, A., Saracco, V., Fogliati, M., Bussolino, C., Mete, F., Gino, M., Vigorito, C., Cittadini, A., Moreo, G., Prolo, S., Pina, G., Ballestrero, A., Ferrando, F., Gonella, R., Cerminara, D., Berra, S., Dassi, S., Nava, M. C., Graziella, B., Baldassarre, S., Fragapani, S., Gruden, G., Galanti, G., Mascherini, G., Petri, C., Stefani, L., Girino, M., Piccinelli, V., Nasso, F., Gioffre, V., Pasquale, M., Sechi, L., Catena, C., Colussi, G., Cavarape, A., da Porto, A., Passariello, N., Rinaldi, L., Berti, F., Famularo, G., Tarsitani, P., Castello, R., Pasino, M., Ceda, G. P., Maggio, M. G., Morganti, S., Artoni, A., Grossi, M., Del Giacco, S., Firinu, D., Costanzo, G., Argiolas, G., Montalto, G., Licata, A., Montalto, F. A., Corica, F., Basile, G., Catalano, A., Bellone, F., Principato, C., Malatino, L., Stancanelli, B., Terranova, V., Di Marca, S., Di Quattro, R., la Malfa, L., Caruso, R., Mecocci, P., Ruggiero, C., Boccardi, V., Meschi, T., Ticinesi, A., Nouvenne, A., Minuz, P., Fondrieschi, L., Imperiale, G. N., Pirisi, M., Fra, G. P., Sola, D., Bellan, M., Porta, M., Riva, P., Quadri, R., Larovere, E., Novelli, M., Scanzi, G., Mengoli, C., Provini, S., Ricevuti, L., Simeone, E., Scurti, R., Tolloso, F., Tarquini, R., Valoriani, A., Dolenti, S., Vannini, G., Volpi, R., Bocchi, P., Vignali, A., Harari, S., Lonati, C., Napoli, F., Aiello, I., Landolfi, R., Montalto, M., Mirijello, A., Ghidoni, S., Salvatore, T., Monaco, L., Ricozzi, C., Pilotto, A., Indiano, I., and Gandolfo, F.

Subjects
2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Aged, Humans, Italy, Hospitals, Internal Medicine, MEDLINE, geriatric, Socio-culturale, law.invention, lockdown, Hospital, Patient Transport, law, Pandemic, Hospital discharge, medicine, Aged, Hospitals, Humans, Internal Medicine, Italy, Letter to the Editor, Internal medicine, LS7_9, business.industry, geriatric patients, medicine.disease, Intensive care unit, Internal medicine, geriatric patients, lockdown, covid-19, covid-19, Medical emergency, business, Human
Abstract

A total of 48 internal medicine or geriatric wards among the 93 adhering to the register REPOSI answered an online questionnaire aimed to investigate the characteristics and activities of converted and non-converted wards in the crucial period of the first wave of the epidemic, 22 February-4 May 2020

Published
2021

47. Clinical relevance of clonal hematopoiesis in persons aged ≥80 years

Author

Aurelio Malabaila, Maria De Santis, Paolo Detoma, Erica Travaglino, Alessia A. Galbussera, Elena Saba, Emma Riva, Rocco Piazza, Marta Ubezio, Maria Elena Bicchieri, Armando Santoro, Gianluigi Condorelli, Matteo Bersanelli, Sara Mandelli, Chiara Chiereghin, George S. Vassiliou, Stefano Duga, Paola Allavena, Francesco Passamonti, Efrem Civilini, Claudia Sala, Matteo Zampini, Luca Sala, Giovanni Corrao, Francesc Solé, Uwe Platzbecker, Karolina Malik, Ettore Mosca, N. Manes, Matteo G. Della Porta, Ugo Lucca, Alessia Campagna, Claudia Saitta, Mauro Tettamanti, Torsten Haferlach, Gastone Castellani, Wolfgang Kern, Laura Giordano, Clelia Peano, Giulia Soldà, Cristina Astrid Tentori, Giulia Maggioni, Stefano Rosso, Manja Meggendorfer, Roberto Zanetti, Chiara Milanesi, Elena Riva, Rosanna Asselta, Pierre Fenaux, Alberto Termanini, Marianna Rossi, Niccolo Bolli, Carlo Selmi, Lucio Morabito, Antonio Russo, Rossi M., Meggendorfer M., Zampini M., Tettamanti M., Riva E., Travaglino E., Bersanelli M., Mandelli S., Antonella Galbussera A., Mosca E., Saba E., Chiereghin C., Manes N., Milanesi C., Ubezio M., Morabito L., Peano C., Solda G., Asselta R., Duga S., Selmi C., De Santis M., Malik K., Maggioni G., Bicchieri M., Campagna A., Tentori C.A., Russo A., Civilini E., Allavena P., Piazza R., Corrao G., Sala C., Termanini A., Giordano L., Detoma P., Malabaila A., Sala L., Rosso S., Zanetti R., Saitta C., Condorelli G., Passamonti F., Santoro A., Sole F., Platzbecker U., Fenaux P., Bolli N., Castellani G., Kern W., Vassiliou G.S., Haferlach T., Lucca U., Della Porta M.G., Rossi, M, Meggendorfer, M, Zampini, M, Tettamanti, M, Riva, E, Travaglino, E, Bersanelli, M, Mandelli, S, Galbussera, A, Mosca, E, Saba, E, Chiereghin, C, Manes, N, Milanesi, C, Ubezio, M, Morabito, L, Peano, C, Soldà, G, Asselta, R, Duga, S, Selmi, C, De Santis, M, Malik, K, Maggioni, G, Bicchieri, M, Campagna, A, Tentori, C, Russo, A, Civilini, E, Allavena, P, Piazza, R, Corrao, G, Sala, C, Termanini, A, Giordano, L, Detoma, P, Malabaila, A, Sala, L, Rosso, S, Zanetti, R, Saitta, C, Condorelli, G, Passamonti, F, Santoro, A, Sole, F, Platzbecker, U, Fenaux, P, Bolli, N, Castellani, G, Kern, W, Vassiliou, G, Haferlach, T, Lucca, U, and Della Porta, M

Subjects
Oncology, Male, Myeloid, Coronary Disease, Biochemistry, Arthritis, Rheumatoid, hemic and lymphatic diseases, aged adult, 80 and over, follow-up, cytopenia, Age Factor, Aged, 80 and over, Myeloid Neoplasia, medicine.diagnostic_test, Age Factors, leukemia, vascular disease, Hematology, anemia, myeloid neoplasms, Leukemia, Haematopoiesis, medicine.anatomical_structure, Leukemia, Myeloid, hematopoiesi, Female, Human, medicine.medical_specialty, Anemia, Immunology, Myelodysplastic Syndrome, Myeloid Neoplasm, Internal medicine, medicine, clonal hematopoiesis, Humans, mean corpuscular volume analyse, Clinical significance, coronary heart disease, Red blood cell indices, Cytopenia, business.industry, mutational screening, Cell Biology, medicine.disease, Myelodysplastic Syndromes, Mutation, Clonal Hematopoiesi, business, hematologic neoplasm
Abstract

Clonal hematopoiesis of indeterminate potential (CHIP) is associated with increased risk of cancers and inflammation-related diseases. This phenomenon becomes common in persons aged ≥80 years, in whom the implications of CHIP are not well defined. We performed a mutational screening in 1794 persons aged ≥80 years and investigated the relationships between CHIP and associated pathologies. Mutations were observed in one-third of persons aged ≥80 years and were associated with reduced survival. Mutations in JAK2 and splicing genes, multiple mutations (DNMT3A, TET2, and ASXL1 with additional genetic lesions), and variant allele frequency ≥0.096 had positive predictive value for myeloid neoplasms. Combining mutation profiles with abnormalities in red blood cell indices improved the ability of myeloid neoplasm prediction. On this basis, we defined a predictive model that identifies 3 risk groups with different probabilities of developing myeloid neoplasms. Mutations in DNMT3A, TET2, ASXL1, or JAK2 were associated with coronary heart disease and rheumatoid arthritis. Cytopenia was common in persons aged ≥80 years, with the underlying cause remaining unexplained in 30% of cases. Among individuals with unexplained cytopenia, the presence of highly specific mutation patterns was associated with myelodysplastic-like phenotype and a probability of survival comparable to that of myeloid neoplasms. Accordingly, 7.5% of subjects aged ≥80 years with cytopenia had presumptive evidence of myeloid neoplasm. In summary, specific mutational patterns define different risk of developing myeloid neoplasms vs inflammatory-associated diseases in persons aged ≥80 years. In individuals with unexplained cytopenia, mutational status may identify those subjects with presumptive evidence of myeloid neoplasms.

Published
2021

48. COVID-19 elicits an impaired antibody response against SARS-CoV-2 in patients with haematological malignancies

Author

Francesco Zaja, Filippo Gherlinzoni, Anna Maria Scattolin, Luca Arcaini, Roberto Cairoli, Mario Luppi, Carmen Fava, Patrizia Zappasodi, Matteo G. Della Porta, Monica Bocchia, Valeria Cardinali, Nicola Stefano Fracchiolla, Francesco Passamonti, Giuseppe Visani, M. Ladetto, Enrico Derenzini, Lorenza Bertù, Roberto Mina, Daniele Armiento, B. Mora, Anna Candoni, Alessandro Corso, A. M. Vannucchi, Paolo Corradini, Francesco Lanza, Pellegrino Musto, Agostino Tafuri, Carlo Visco, E. Coviello, Francesco Marchesi, Roberto M. Lemoli, Chiara Cattaneo, Alessandro Busca, Marco Salvini, Sara Galimberti, I. Romano, M. Merli, Mauro Krampera, Alessandra Romano, Paolo Grossi, Michele Cavo, E. O. La Barbera, Mauro Turrini, Livio Pagano, Adriano Venditti, Antonio Pinto, Patrizia Tosi, F. Farina, Riccardo Bruna, L. Petrucci, Massimo Massaia, Monia Marchetti, Carlo Gambacorti Passerini, Francesco Merli, Passamonti, F, Romano, A, Salvini, M, Merli, F, Porta, M, Bruna, R, Coviello, E, Romano, I, Cairoli, R, Lemoli, R, Farina, F, Venditti, A, Busca, A, Ladetto, M, Massaia, M, Pinto, A, Arcaini, L, Tafuri, A, Marchesi, F, Fracchiolla, N, Bocchia, M, Armiento, D, Candoni, A, Krampera, M, Luppi, M, Cardinali, V, Galimberti, S, Cattaneo, C, La Barbera, E, Mina, R, Lanza, F, Visani, G, Musto, P, Petrucci, L, Zaja, F, Grossi, P, Bertu, L, Pagano, L, Corradini, P, Derenzini, E, Marchetti, M, Scattolin, A, Corso, A, Tosi, P, Gherlinzoni, F, Gambacorti Passerini, C, Cavo, M, Fava, C, Turrini, M, Visco, C, Zappasodi, P, Merli, M, Mora, B, Vannucchi, A, Passamonti F., Romano A., Salvini M., Merli F., Porta M.G.D., Bruna R., Coviello E., Romano I., Cairoli R., Lemoli R., Farina F., Venditti A., Busca A., Ladetto M., Massaia M., Pinto A., Arcaini L., Tafuri A., Marchesi F., Fracchiolla N., Bocchia M., Armiento D., Candoni A., Krampera M., Luppi M., Cardinali V., Galimberti S., Cattaneo C., La Barbera E.O., Mina R., Lanza F., Visani G., Musto P., Petrucci L., Zaja F., Grossi P.A., Bertu L., Pagano L., Corradini P., Derenzini E., Marchetti M., Scattolin A.M., Corso A., Tosi P., Gherlinzoni F., Passerini C.G., Cavo M., Fava C., Turrini M., Visco C., Zappasodi P., Merli M., Mora B., Vannucchi A.M., Passamonti, F., Romano, A., Salvini, M., Merli, F., Porta, M. G. D., Bruna, R., Coviello, E., Romano, I., Cairoli, R., Lemoli, R., Farina, F., Venditti, A., Busca, A., Ladetto, M., Massaia, M., Pinto, A., Arcaini, L., Tafuri, A., Marchesi, F., Fracchiolla, N., Bocchia, M., Armiento, D., Candoni, A., Krampera, M., Luppi, M., Cardinali, V., Galimberti, S., Cattaneo, C., La Barbera, E. O., Mina, R., Lanza, F., Visani, G., Musto, P., Petrucci, L., Zaja, F., Grossi, P. A., Bertu, L., Pagano, L., Corradini, P., Derenzini, E., Marchetti, M., Scattolin, A. M., Corso, A., Tosi, P., Gherlinzoni, F., Passerini, C. G., Cavo, M., Fava, C., Turrini, M., Visco, C., Zappasodi, P., Merli, M., Mora, B., and Vannucchi, A. M.

Subjects
Male, Myeloid, Antibodies, Viral, Gastroenterology, SARS‐CoV‐2, 80 and over, Covid-19, SARS-CoV-2, leukemia, lymphoma, myeloma, Viral, Covid‐19, Aged, 80 and over, biology, Hematology, Plasma cell neoplasm, Middle Aged, Adult, Aged, COVID-19, Female, Hematologic Neoplasms, Humans, Immunoglobulin G, Seroconversion, Young Adult, Antibody Formation, Leukemia, medicine.anatomical_structure, Antibody, Human, medicine.medical_specialty, Short Report, Antibodies, NO, Chemoimmunotherapy, Internal medicine, medicine, Hematologic Neoplasm, business.industry, Odds ratio, Settore MED/15, medicine.disease, Covid-19, SARS-CoV-2, leukemia, lymphoma, myeloma, Lymphoma, Settore MED/15 - MALATTIE DEL SANGUE, biology.protein, business
Abstract

COVID-19 is associated with high mortality in patients with haematological malignancies (HM) and rate of seroconversion is unknown. The ITA-HEMA-COV project (NCT04352556) investigated patterns of seroconversion for SARS-CoV-2 IgG in patients with HMs. A total of 237 patients, SARS-CoV-2 PCR-positive with at least one SARS-CoV-2 IgG test performed during their care, entered the analysis. Among these, 62 (26·2%) had myeloid, 121 (51·1%) lymphoid and 54 (22·8%) plasma cell neoplasms. Overall, 69% of patients (164 of 237) had detectable IgG SARS-CoV-2 serum antibodies. Serologically negative patients (31%, 73 of 237) were evenly distributed across patients with myeloid, lymphoid and plasma cell neoplasms. In the multivariable logistic regression, chemoimmunotherapy [odds ratio (OR), 3·42; 95% confidence interval (CI), 1·04–11·21; P=0·04] was associated with a lower rate of seroconversion. This effect did not decline after 180days from treatment withdrawal (OR, 0·35; 95% CI: 0·11–1·13; P=0·08). This study demonstrates a low rate of seroconversion in HM patients and indicates that treatment-mediated immune dysfunction is the main driver. As a consequence, we expect a low rate of seroconversion after vaccination and thus we suggest testing the efficacy of seroconversion in HM patients.

Published
2021

49. SARS-CoV-2 Interstitial Pneumonia Treated With Tocilizumab in a Patient Affected by Classical Hodgkin Lymphoma

Author

Cristiana Carniti, Rodolfo Lanocita, Giulio Cassanello, Chiara Oltolini, Chiara Rusconi, Vincenzo Marasco, Anna Guidetti, Lucio Morabito, Gabriele Papagni, Paolo Corradini, and Matteo G. Della Porta

Subjects
2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Patient affected, business.industry, lcsh:RC633-647.5, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Case Report, Hematology, lcsh:Diseases of the blood and blood-forming organs, Virology, chemistry.chemical_compound, Tocilizumab, chemistry, Classical Hodgkin lymphoma, Medicine, Interstitial pneumonia, business
Published
2020

50. The SPID-GBA study: Sex distribution, Penetrance, Incidence, and Dementia in GBA-PD

Author

Valeria Rimoldi, Giada Melistaccio, Ugo Lucca, Anna Zecchinelli, Stefano Duga, Alessio Di Fonzo, Gianni Pezzoli, Letizia Straniero, Rosanna Asselta, Matteo G. Della Porta, Roberto Cilia, Giulia Solda, Massimo Aureli, and Salvatore Bonvegna

Subjects
0301 basic medicine, medicine.medical_specialty, Disease, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, mental disorders, medicine, Dementia, Genetics (clinical), business.industry, Dementia with Lewy bodies, Incidence (epidemiology), Parkinsonism, Odds ratio, medicine.disease, Penetrance, Confidence interval, 030104 developmental biology, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

ObjectiveTo provide a variant-specific estimate of incidence, penetrance, sex distribution, and association with dementia of the 4 most common Parkinson disease (PD)-associated GBA variants, we analyzed a large cohort of 4,923 Italian unrelated patients with primary degenerative parkinsonism (including 3,832 PD) enrolled in a single tertiary care center and 7,757 ethnically matched controls.MethodsThe p.E326K, p.T369M, p.N370S, and p.L444P variants were screened using an allele-specific multiplexed PCR approach. All statistical procedures were performed using R or Plink v1.07.ResultsAmong the 4 analyzed variants, the p.L444P confirmed to be the most strongly associated with disease risk for PD, PD dementia (PDD), and dementia with Lewy bodies (DLB) (odds ratio [OR] for PD 15.63, 95% confidence interval [CI] = 8.04–30.37, p = 4.97*10−16; OR for PDD 29.57, 95% CI = 14.07–62.13, p = 3.86*10−19; OR for DLB 102.7, 95% CI = 31.38–336.1, p = 1.91*10−14). However, an unexpectedly high risk for dementia was conferred by p.E326K (OR for PDD 4.80, 95% CI = 2.87–8.02, p = 2.12*10−9; OR for DLB 12.24, 95% CI = 4.95–30.24, p = 5.71*10−8), which, on the basis of the impact on glucocerebrosidase activity, would be expected to be mild. The 1.5–2:1 male sex bias described in sporadic PD was lost in p.T369M carriers. We also showed that PD penetrance for p.L444P could reach the 15% at age 75 years.ConclusionsWe report a large monocentric study on GBA-PD assessing mutation-specific data on the sex distribution, penetrance, incidence, and association with dementia of the 4 most frequent deleterious variants in GBA.

Published
2020

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