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Article ; Online: Measurable residual disease in chronic lymphocytic leukemia. Where do we stand?

Del Giudice, Ilaria / Foà, Robin

2023 Volume 37, Issue 12, Page(s) 2339–2342

MeSH term(s)	Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; Antineoplastic Combined Chemotherapy Protocols ; Neoplasm, Residual/drug therapy
Language	English
Publishing date	2023-10-14
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	807030-1
ISSN	1476-5551 ; 0887-6924
ISSN (online)	1476-5551
ISSN	0887-6924
DOI	10.1038/s41375-023-02066-w
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Article: Research Topic: Measurable Residual Disease in Hematologic Malignancies. Can digital droplet PCR improve measurable residual disease monitoring in chronic lymphoid malignancies?

Assanto, Giovanni Manfredi / Del Giudice, Ilaria / Della Starza, Irene / Soscia, Roberta / Cavalli, Marzia / Cola, Mattia / Bellomarino, Vittorio / Di Trani, Mariangela / Guarini, Anna / Foà, Robin

Frontiers in oncology

2023 Volume 13, Page(s) 1152467

Abstract: Minimal/measurable residual disease (MRD) monitoring is progressively changing the management of hematologic malignancies. The possibility of detecting the persistence/reappearance of disease in patients in apparent clinical remission offers a refined ... ...

Abstract	Minimal/measurable residual disease (MRD) monitoring is progressively changing the management of hematologic malignancies. The possibility of detecting the persistence/reappearance of disease in patients in apparent clinical remission offers a refined risk stratification and a treatment decision making tool. Several molecular techniques are employed to monitor MRD, from conventional real-time quantitative polymerase chain reaction (RQ-PCR) to next generation sequencing and digital droplet PCR (ddPCR), in different tissues or compartments through the detection of fusion genes, immunoglobulin and T-cell receptor gene rearrangements or disease-specific mutations. RQ-PCR is still the gold standard for MRD analysis despite some limitations. ddPCR, considered the third-generation PCR, yields a direct, absolute, and accurate detection and quantification of low-abundance nucleic acids. In the setting of MRD monitoring it carries the major advantage of not requiring a reference standard curve built with the diagnostic sample dilution and of allowing to reduce the number of samples below the quantitative range. At present, the broad use of ddPCR to monitor MRD in the clinical practice is limited by the lack of international guidelines. Its application within clinical trials is nonetheless progressively growing both in acute lymphoblastic leukemia as well as in chronic lymphocytic leukemia and non-Hodgkin lymphomas. The aim of this review is to summarize the accumulating data on the use of ddPCR for MRD monitoring in chronic lymphoid malignancies and to highlight how this new technique is likely to enter into the clinical practice.
Language	English
Publishing date	2023-03-14
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2023.1152467
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Article: Impact of Sars-CoV-2 Prophylaxis with Tixagevimab-Cilgavimab in High-Risk Patients with B-Cell Malignancies: A Single-Center Retrospective Study.

Assanto, Giovanni Manfredi / Totaro, Matteo / Poggiali, Rebecca / Delli Paoli, Adele / Annechini, Giorgia / D'Elia, Gianna Maria / Aji, Francesco / Petrucci, Luigi / Fazio, Francesca / Del Giudice, Ilaria / Martelli, Maurizio / Micozzi, Alessandra / Gentile, Giuseppe

Mediterranean journal of hematology and infectious diseases

2023 Volume 15, Issue 1, Page(s) e2023061

Language	English
Publishing date	2023-11-01
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2674750-9
ISSN	2035-3006
ISSN	2035-3006
DOI	10.4084/MJHID.2023.061
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Article ; Online: Sialylation regulates migration in chronic lymphocytic leukemia.

Natoni, Alessandro / Cerreto, Marina / De Propris, Maria Stefania / Del Giudice, Ilaria / Soscia, Roberta / Peragine, Nadia / Intoppa, Stefania / Milani, Maria Laura / Guarini, Anna / Foà, Robin

Haematologica

2023 Volume 108, Issue 7, Page(s) 1851–1860

Abstract: Sialylation is the terminal addition of sialic acid to underlying glycans. It plays a prominent role in cell adhesion and immune regulation. Sialylated structures found on adhesion molecules, such as CD49d, mediate the interactions between cancer cells ... ...

Abstract	Sialylation is the terminal addition of sialic acid to underlying glycans. It plays a prominent role in cell adhesion and immune regulation. Sialylated structures found on adhesion molecules, such as CD49d, mediate the interactions between cancer cells and the microenvironment, facilitating metastatic seeding in target organs. Chronic lymphocytic leukemia (CLL) is a clonal B-cell malignancy characterized by the accumulation of CD5-positive B cells in the peripheral blood, bone marrow and lymph nodes. CLL cells proliferate mainly in the lymph node "proliferation centers", where the microenvironment provides pro-survival signals. Thus, migration and homing into these protective niches play a crucial role in CLL biology. In recent years, therapeutic strategies aimed at inducing the egress of CLL cells from the lymph nodes and bone marrow into the circulation have been highly successful. In this study, the sialylation status of 79 untreated and 24 ibrutinib-treated CLL patients was characterized by flow cytometry. Moreover, the effect of sialic acid removal on migration was tested by a transwell assay. Finally, we examined the sialylation status of CD49d by Western blot analysis. We found that CLL cells are highly sialylated, particularly those characterized by an "activated" immune phenotype. Notably, sialylation regulates CLL migration through the post-translational modification of CD49d. Finally, we showed that therapeutic agents that induce CLL mobilization from their protective niches, such as ibrutinib, modulate sialic acid levels. We propose that sialylation is an important regulator of CLL trafficking and may represent a novel target to further improve CLL therapy.
MeSH term(s)	Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; N-Acetylneuraminic Acid/metabolism ; Bone Marrow/pathology ; B-Lymphocytes/metabolism ; Integrin alpha4/metabolism ; Tumor Microenvironment
Chemical Substances	N-Acetylneuraminic Acid (GZP2782OP0) ; Integrin alpha4 (143198-26-9)
Language	English
Publishing date	2023-07-01
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2022.281999
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Article ; Online: Additional lesions identified by genomic microarrays are associated with an inferior outcome in low-risk chronic lymphocytic leukaemia patients.

Rigolin, Gian Matteo / Traversa, Alice / Caputo, Viviana / Del Giudice, Ilaria / Bardi, Antonella / Saccenti, Elena / Raponi, Sara / Ilari, Caterina / Cafforio, Luciana / Giovannetti, Agnese / Pizzuti, Antonio / Guarini, Anna / Foà, Robin / Cuneo, Antonio

British journal of haematology

2023 Volume 202, Issue 5, Page(s) 953–959

Abstract: We explored the relevance of genomic microarrays (GM) in the refinement of prognosis in newly diagnosed low-risk chronic lymphocytic leukaemia (CLL) patients as defined by isolated del(13q) or no lesions by a standard 4 probe fluorescence in situ ... ...

Abstract	We explored the relevance of genomic microarrays (GM) in the refinement of prognosis in newly diagnosed low-risk chronic lymphocytic leukaemia (CLL) patients as defined by isolated del(13q) or no lesions by a standard 4 probe fluorescence in situ hybridization (FISH) analysis. Compared to FISH, additional lesions were detected by GM in 27 of the 119 patients (22.7%). The concordance rate between FISH and GM was 87.4%. Discordant results between cytogenetic banding analysis (CBA) and GM were observed in 45/119 cases (37.8%) and were mainly due to the intrinsic characteristics of each technique. The presence of additional lesions by GM was associated with age > 65 years (p = 0.047), advanced Binet stage (p = 0.001), CLL-IPI score (p < 0.001), a complex karyotype (p = 0.004) and a worse time-to-first treatment in multivariate analysis (p = 0.009). Additional lesions by GM were also significantly associated with a worse time-to-first treatment in the subset of patients with wild-type TP53 and mutated IGHV (p = 0.025). In CLL patients with low-risk features, the presence of additional lesions identified by GM helps to identify a subset of patients with a worse outcome that could be proposed for a risk-adapted follow-up and for early treatment including targeted agents within clinical trials.
MeSH term(s)	Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/pathology ; In Situ Hybridization, Fluorescence ; Prognosis ; Risk Factors ; Genomics
Language	English
Publishing date	2023-06-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.18946
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Article ; Online: Impact of anti-SARS-CoV-2 monoclonal antibodies in the management of patients with lymphoma and COVID19: A retrospective study.

Assanto, Giovanni Manfredi / Di Rocco, Alice / Malfona, Francesco / Capriata, Marcello / Del Giudice, Ilaria / Petrucci, Luigi / Girardi, Paola / D'Elia, Gianna Maria / Martelli, Maurizio / Gentile, Giuseppe / Micozzi, Alessandra / Pulsoni, Alessandro

Hematological oncology

2022 Volume 41, Issue 3, Page(s) 343–353

Abstract: COVID19 in patients affected by lymphoma represents an important challenge because of the higher mortality rate. Anti-SARS-CoV-2 monoclonal antibodies (anti-S MoAbs) appear promising in this setting. We report a monocentric retrospective study including ... ...

Abstract	COVID19 in patients affected by lymphoma represents an important challenge because of the higher mortality rate. Anti-SARS-CoV-2 monoclonal antibodies (anti-S MoAbs) appear promising in this setting. We report a monocentric retrospective study including 176 patients affected by lymphoma which developed SARS-CoV-2 infection since the start of COVID19 pandemic. Overall, mortality was 13.1%, with a decreasing trend between first waves to the last wave of pandemic (18.5% vs. 9.4%, p 0.076). Patients receiving anti-S MoAbs (41.3%) showed inferior mortality rate (overall survival, OS 93.2% vs. 82.7%, p 0.025) with no serious toxicity, reduced documented pneumonia (26% vs. 33%, p 0.005), and reduced need of oxygen support (14.5% vs. 35.7%, p 0.003). Among patients who received 3 doses of vaccine, the employment of anti-COVID MoAbs showed a trend of superior survival versus those who did not receive Anti-S MoAbs (OS rates 97.3% vs. 84.2%, p 0.064). On multivariate analysis, active haematological disease (OS 72% (HR 2.49 CI 1.00-6.41), bendamustine exposure (OS 60% HR 4.2 CI 1.69-10.45) and at least one comorbidity (HR 6.53 CI 1.88-22.60) were independent prognostic factors for death. Our study confirms the adverse prognostic role of COVID-19 in lymphoma patients in presence of active disease, comorbidities and previous exposure to bendamustine. In our experience, anti-S MoAbs represented a therapeutic option in vaccinated patients.
MeSH term(s)	Humans ; COVID-19 ; Retrospective Studies ; Bendamustine Hydrochloride ; SARS-CoV-2 ; Lymphoma/drug therapy ; Antibodies, Monoclonal/therapeutic use
Chemical Substances	Bendamustine Hydrochloride (981Y8SX18M) ; Antibodies, Monoclonal
Language	English
Publishing date	2022-12-30
Publishing country	England
Document type	Journal Article
ZDB-ID	604884-5
ISSN	1099-1069 ; 0278-0232
ISSN (online)	1099-1069
ISSN	0278-0232
DOI	10.1002/hon.3113
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Article ; Online: Early CD49d downmodulation in chronic lymphocytic leukemia patients treated front-line with ibrutinib plus rituximab predicts long-term response.

Peragine, Nadia / De Propris, Maria Stefania / Intoppa, Stefania / Milani, Maria Laura / Mauro, Francesca Romana / Cuneo, Antonio / Rigolin, Gian Matteo / Del Giudice, Ilaria / Foà, Robin / Guarini, Anna

Leukemia & lymphoma

2022 Volume 63, Issue 12, Page(s) 2982–2986

MeSH term(s)	Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; Rituximab/therapeutic use ; Piperidines/therapeutic use ; Adenine ; Antineoplastic Combined Chemotherapy Protocols/adverse effects
Chemical Substances	ibrutinib (1X70OSD4VX) ; Rituximab (4F4X42SYQ6) ; Piperidines ; Adenine (JAC85A2161)
Language	English
Publishing date	2022-08-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	1042374-6
ISSN	1029-2403 ; 1042-8194
ISSN (online)	1029-2403
ISSN	1042-8194
DOI	10.1080/10428194.2022.2105324
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Article: High Basal Maximal Standardized Uptake Value (SUV

Assanto, Giovanni Manfredi / Ciotti, Giulia / Brescini, Mattia / De Luca, Maria Lucia / Annechini, Giorgia / D'Elia, Gianna Maria / Agrippino, Roberta / Del Giudice, Ilaria / Martelli, Maurizio / Chiaravalloti, Agostino / Pulsoni, Alessandro

Cancers

2021 Volume 13, Issue 12

Abstract: Background: Despite that the unfavorable prognostic role of a high Total Metabolic Tumor Volume (TMTV) in Follicular Lymphoma has been demonstrated, the role of SUV: Patients and methods: We performed a retrospective observational monocentric cohort ... ...

Abstract	Background: Despite that the unfavorable prognostic role of a high Total Metabolic Tumor Volume (TMTV) in Follicular Lymphoma has been demonstrated, the role of SUV Patients and methods: We performed a retrospective observational monocentric cohort study. All patients affected by FL who underwent a basal PET/CT were included. Two subgroups were identified and compared in terms of PFS and OS: (A) Basal SUV Results: Ninety-four patients were included, 34 in group A (36.2%) and 60 in group B (63.8%). The PFS at two years was comparable in the two groups (97%). The five-year PFS was 73.5% for group A and 95% for group B ( Conclusion: A high FDG uptake favorably correlated with PFS. A low basal SUV
Language	English
Publishing date	2021-06-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13122876
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Article ; Online: Treatment with ibrutinib does not induce a

Cafforio, Luciana / Raponi, Sara / Cappelli, Luca Vincenzo / Ilari, Caterina / Soscia, Roberta / De Propris, Maria Stefania / Mariglia, Paola / Rigolin, Gian Matteo / Bardi, Antonella / Peragine, Nadia / Piciocchi, Alfonso / Arena, Valentina / Mauro, Francesca Romana / Cuneo, Antonio / Guarini, Anna / Foa, Robin / Del Giudice, Ilaria

Haematologica

2022 Volume 107, Issue 1, Page(s) 334–337

MeSH term(s)	Adenine/analogs & derivatives ; Clonal Evolution/genetics ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; Piperidines ; Tumor Suppressor Protein p53/genetics
Chemical Substances	Piperidines ; TP53 protein, human ; Tumor Suppressor Protein p53 ; ibrutinib (1X70OSD4VX) ; Adenine (JAC85A2161)
Language	English
Publishing date	2022-01-01
Publishing country	Italy
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2020.263715
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Article ; Online: Blast morphology in the diagnostic work-up of Ph-like acute lymphoblastic leukemia.

Fazio, Francesca / Cunsolo, Gabriella / Mancini, Francesca / De Propris, Maria Stefania / Piciocchi, Alfonso / Arena, Valentina / Messina, Monica / Ansuinelli, Michela / Taherinasab, Akram Taherinasab / Apicella, Valerio / Vitale, Antonella / Chiaretti, Sabina / Guarini, Anna / Del Giudice, Ilaria / Foà, Robin

Leukemia & lymphoma

2022 Volume 63, Issue 6, Page(s) 1512–1514

MeSH term(s)	Blast Crisis/diagnosis ; Humans ; Philadelphia Chromosome ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis
Language	English
Publishing date	2022-02-08
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	1042374-6
ISSN	1029-2403 ; 1042-8194
ISSN (online)	1029-2403
ISSN	1042-8194
DOI	10.1080/10428194.2022.2032035
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