Clara Deambrogi

Università degli Studi del Piemonte Orientale “Amedeo Avogadro”

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Gianluca Gaïdano

Università degli Studi del Piemonte Orientale “Amedeo Avogadro”

105

Davide Rossi

Institute of Oncology Research

Valeria Spina

Ente Ospedaliero Cantonale

Silvia Rasi

Università degli Studi del Piemonte Orientale “Amedeo Avogadro”

Valter Gattei

Centro di Riferimento Oncologico

Lorenzo De Paoli

Azienda Ospedaliera Sant'Andrea

Michaela Cerri

Università degli Studi del Piemonte Orientale “Amedeo Avogadro”

Francesco Forconi

University of Southampton

Daniela Capello

Università degli Studi del Piemonte Orientale “Amedeo Avogadro”

Alessio Bruscaggin

Institute of Oncology Research

Cooperative Institutions

Università degli Studi del Piemonte Orientale “Amedeo Avogadro”

145

Istituti di Ricovero e Cura a Carattere Scientifico

116

Ospedale Maggiore

Azienda Ospedaliero Universitaria Maggiore della Carita

University of Turin

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Institute of Oncology Research

University of Bologna

Centro di Riferimento Oncologico

Università della Svizzera italiana

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A randomized clinical study on the impact of Comprehensive Geriatric Assessment (CGA) based interventions on the quality of life of elderly, frail, onco-hematologic patients candidate to anticancer therapy: protocol of the ONCO-Aging study

BMC Geriatrics (2021)

Abdurraouf Mokhtar Mahmoud Federica Biello Paola Maggiora Riccardo Bruna Giovanni Burrafato

Abstract Background Age is considered as one of the most important risk-factor for many types of solid and hematological cancers, as their incidence increases with age in parallel to the ever-growing elderly population. Moreover, cancer incidence is constantly increasing as a consequence of the increase in life expectancy that favors the process of cellular senescence. Geriatric assessment has been increasingly recognized as predictive and prognostic instrument to detect frailty in older adults with cancer. In particular, the G8 score is a simple and reproducible instrument to identify elderly patients who should undergo full geriatric evaluation. Due to their frailty, elderly patients may be often under-treated and a therapeutic choice based also on a comprehensive geriatric assessment (CGA) is recommended. With these premises, we aim to test the impact of the CGA based interventions on the quality of life (QoL) of frail elderly onco-hematological patients, identified by the G8 screening, candidate for innovative target directed drugs or treatments including the combination of radiotherapy and chemotherapy (RT + CT). Methods Patients aged > 65 years, candidate to target directed agents or to RT + CT treatments are screened for frailty by the G8 test; those patients classified as frail (G8 ≤ 14) are randomized to receive a CGA at baseline or to conventional care. The primary endpoint is QoL, assessed by EORTC QLQ-C30C. As collateral biological study, the potential prognostic/predictive role of T-cell senescence and myeloid derived suppressor cells (MDSC) are evaluated on plasma samples. Discussion This trial will contribute to define the impact of CGA on the management of frail elderly onco-hematologic patients candidate to innovative biological drugs or to integrated schedules with the association of RT + CT. Furthermore, the use of plasma samples to assess the potential prognostic value of imbalance of immune-competent cells is expected to contribute to the individualized care of elderly patients, resulting into a fine tuning of the therapeutic strategies. Trial registration ClinicalTrials.gov ID: NCT04478916 . registered July 21, 2020 – retrospectively registered.

Clinical endpoint

10.1186/s12877-021-02237-3

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Citations (7)

Genome Wide-DNA Profiling of Richter’s Syndrome-Diffuse Large B-Cell Lymphoma (RS-DLBCL): Differences with De Novo DLBCL and Possible Mechanisms of Transformation from Chronic Lymphocytic Leukemia (CLL).

Blood (2008)

Francesco Bertoni Marta Scandurra Michaela Cerri Clara Deambrogi Paola M. V. Rancoita

SNP array

10.1182/blood.v112.11.2067.2067

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Citations (1)

Digital PCR improves the quantitation of DMR and the selection of CML candidates to TKIs discontinuation

Cancer Medicine (2019)

Simona Bernardi Michele Malagola Camilla Zanaglio Nicola Polverelli Elif Dereli Eke

Abstract Treatment‐free remission (TFR) by tyrosine kinase inhibitors (TKI) discontinuation in patients with deep molecular response (DMR) is a paramount goal in the current chronic myeloid leukemia (CML) therapeutic strategy. The best DMR level by real‐time quantitative PCR (RT‐qPCR) for TKI discontinuation is still a matter of debate. To compare the accuracy of digital PCR (dPCR) and RT‐qPCR for BCR‐ABL1 transcript levels detection, 142 CML patients were monitored for a median time of 24 months. Digital PCR detected BCR‐ABL1 transcripts in the RT‐qPCR undetectable cases. The dPCR analysis of the samples, grouped by the MR classes, revealed a significant difference between MR 4.0 and MR 4.5 ( P = 0.0104) or MR 5.0 ( P = 0.0032). The clinical and hematological characteristics of the patients grouped according to DMR classes (MR 4.0 vs MR 4.5‐5.0 ) were superimposable. Conversely, patients with dPCR values <0.468 BCR‐ABL1 copies/µL (as we previously described) showed a longer DMR duration ( P = 0.0220) and mainly belonged to MR 4.5‐5.0 ( P = 0.0442) classes compared to patients with higher dPCR values. Among the 142 patients, 111 (78%) discontinued the TKI treatment; among the 111 patients, 24 (22%) lost the MR 3.0 or MR 4.0 . RT‐qPCR was not able to discriminate patients with higher risk of MR loss after discontinuation ( P = 0.8100). On the contrary, according to dPCR, 12/25 (48%) patients with BCR‐ABL1 values ≥0.468 and 12/86 (14%) patients with BCR‐ABL1 values <0.468 lost DMR in this cohort, respectively ( P = 0.0003). Treatment‐free remission of patients who discontinued TKI with a dPCR <0.468 was significantly higher compared to patients with dPCR ≥ 0.468 (TFR at 2 years 83% vs 52% P = 0.0017, respectively). In conclusion, dPCR resulted in an improved recognition of stable DMR and of candidates to TKI discontinuation.

Discontinuation

10.1002/cam4.2087

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Aberrant somatic hypermutation in primary mediastinal large B-cell lymphoma

Leukemia (2005)

Davide Rossi M Cerri Daniela Capello Clara Deambrogi Eva Berra

10.1038/sj.leu.2403982

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Human herpesvirus type 8-associated primary lymphomatous effusion in an elderly HIV-negative patient: clinical and molecular characterization.

PubMed (2002)

Daniela Buonaiuto Davide Rossi Francesca Guidetti Daniela Vivenza Eva Berra

Primary lymphomatous effusions are defined as lymphomas presenting in the serous body cavities in the absence of clinically identifiable tumor masses. Recently, a peculiar type of primary lymphomatous effusion associated with tumor clone infection by human herpesvirus type 8 (HHV-8) and preferentially arising in HIV-positive patients has been described and termed as primary effusion lymphoma (PEL). This report describes a case of PEL which has developed in a HIV-negative, 92-year-old man with longstanding Mediterranean Kaposi's sarcoma, a disease also associated with HHV-8 infection. The patient presented with pleural and ascitic effusions in the absence of solid masses within the lungs, mediastinum, thoracic wall or abdominal cavity. The effusions consisted of malignant lymphocytes with morphologic features bridging immunoblastic and anaplastic cells. Immunophenotypic studies revealed that the lymphoma population expressed an antigenic profile consistent with PEL, i.e. the absence of common B- and T-cell markers (non-B, non-T phenotype) coupled to CD138 positivity. Molecular analysis demonstrated infection of the tumor clone by HHV-8 as well as monoclonally rearranged immunoglobulin genes, consistent with a B-cell histogenesis of the lymphoma. In addition, this PEL case harbored PAX-5 gene mutations, which have been recently demonstrated as a key feature of the proto-oncogene hypermutation process involved in the pathogenesis of some lymphoma types. Following two courses of etoposide and prednisone, a partial remission was achieved. The patient died of liver failure 3 months after the diagnosis of PEL. Overall, this case report illustrates the need for an integrated diagnostic approach based on clinical features, morphology, immunophenotype, and molecular genetics to primary lymphomatous effusions.

Primary effusion lymphoma

clone (Java method)

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Circulating tumor DNA reveals genetics, clonal evolution, and residual disease in classical Hodgkin lymphoma

Blood (2018)

Valeria Spina Alessio Bruscaggin Annarosa Cuccaro Maurizio Martini Martina Di Trani

Minimal Residual Disease

Circulating tumor DNA

10.1182/blood-2017-11-812073

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Citations (280)

Data from Stereotyped B-Cell Receptor Is an Independent Risk Factor of Chronic Lymphocytic Leukemia Transformation to Richter Syndrome

Davide Rossi Valeria Spina Michaela Cerri Silvia Rasi Clara Deambrogi

<div>AbstractPurpose: Few biological prognosticators are useful for prediction of Richter syndrome (RS), representing the transformation of chronic lymphocytic leukemia (CLL) to aggressive lymphoma. Stereotyped B-cell receptors (BCR) may have prognostic effect in CLL progression. We tested the prognostic effect of stereotyped BCR for predicting RS transformation.Experimental Design: The prevalence of stereotyped BCR was compared in RS (n = 69) versus nontransformed CLL (n = 714) by a case-control analysis. Subsequently, the effect of stereotyped BCR at CLL diagnosis on risk of RS transformation was actuarially assessed in a consecutive CLL series (n = 753).Results: RS (n = 69) displayed a higher prevalence of stereotyped BCR (P < 0.001) compared with nontransformed CLL. The actuarial risk of RS transformation was significantly higher in CLL carrying stereotyped BCR (P < 0.001). Among BCR subsets most represented in CLL, subset 8 using IGHV4-39/IGHD6-13/IGHJ5 carried the highest risk of RS transformation [hazard ratio (HR), 24.50; P < 0.001]. Multivariate analysis selected stereotyped BCR (HR, 3.33; P = 0.001) and IGHV4-39 usage (HR, 4.03; P = 0.004) as independent predictors of RS transformation. The combination of IGHV4-39 usage and stereotyped BCR in the same patient identified CLL with a very high risk of RS transformation (5-year risk, 68.7%). The risk carried by stereotyped BCR and IGHV4-39 usage was specific for RS transformation and had no effect on CLL progression without transformation.Conclusions: Analysis of BCR features may help identify CLL patients at risk of RS. A close monitoring and a careful biopsy policy may help early recognition of RS in CLL patients using stereotyped BCR, particularly if combined with IGHV4-39.</div>

breakpoint cluster region

10.1158/1078-0432.c.6517491

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Data from The Prognostic Value of TP53 Mutations in Chronic Lymphocytic Leukemia Is Independent of Del17p13: Implications for Overall Survival and Chemorefractoriness

Davide Rossi Michaela Cerri Clara Deambrogi Elisa Sozzi Stefania Cresta

<div>AbstractPurpose: Del17p13 predicts poor outcome and chemorefractoriness in chronic lymphocytic leukemia (CLL). Conversely, it is unknown whether TP53 mutations carry any prognostic value independent of del17p13. We tested the independent prognostic value of TP53 mutations in CLL.Experimental Design: The study was based on a consecutive series of 308 CLL. DNA sequencing of TP53 exons 2 to 10 and del17p13 interphase fluorescence in situ hybridization were done at CLL diagnosis. Study end points were survival and chemorefractoriness.Results: At diagnosis, TP53 mutations (n = 32) occurred in 31 of 308 (10.0%) patients. Of all CLL showing TP53 disruption by either mutation and/or deletion (n = 44), 10 cases (22.7%) showed TP53 mutations in the absence of del17p13. Multivariate analysis selected TP53 mutations (hazard ratio, 3.20; P = 0.002) as an independent predictor of overall survival after adjustment for del17p13. Also, multivariate analysis selected TP53 mutations (hazard ratio, 3.97; P < 0.001) as an independent predictor of chemorefractoriness after adjustment for del17p13. Compared with cases without TP53 alterations, CLL harboring any type of TP53 disruption (mutation only, del17p13 only, or both mutation and del17p13) uniformly displayed a high prevalence of unfavorable prognosticators and poor outcome. Analysis of sequential CLL samples showed the acquisition of new or additional TP53 alterations at the time of chemorefractoriness.Conclusions: These data show that (a) TP53 mutations are an independent predictor of short survival and chemorefractoriness, and (b) that CLL presenting with TP53 mutations without del17p13 fare as poorly as CLL carrying del17p13. Because CLL harboring TP53 mutations without del17p13 are currently not recognized by conventional diagnostic strategies, these results may be relevant for a comprehensive prognostic characterization of CLL.</div>

10.1158/1078-0432.c.6517548.v1

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Molecular Clustering on Ctdna May Improve Prognostic Stratification of DLBCL Patients

Blood (2022)

Riccardo Moia Chiara Favini Donatella Talotta Riccardo Dondolin Mohammad Almasry

Liquid biopsy

Daunorubicin

10.1182/blood-2022-162416

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Telomere Length Is An Independent Predictor of Survival, Treatment Requirement and Richter’s Syndrome Transformation in Chronic Lymphocytic Leukemia.

Blood (2008)

Davide Rossi Chiara Lobetti Bodoni Elisa Genuardi Luigia Monitillo Daniela Drandi

10.1182/blood.v112.11.1052.1052

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Citations (1)