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Article ; Online: A narrative review of consolidation strategies for young and fit patients with newly-diagnosed primary central nervous system lymphoma.

Steffanoni, Sara / Calimeri, Teresa / Anzalone, Nicoletta / Mastaglio, Sara / Bernardi, Massimo / Ferreri, Andrés Jm

2022 Volume 15, Issue 1, Page(s) 33–43

Abstract: Introduction: The modern treatment of patients with primary central nervous system lymphoma (PCNSL) consists of two phases: induction, currently represented by a high-dose-methotrexate-based polychemotherapy, and consolidation. The optimal consolidation ...

Abstract	Introduction: The modern treatment of patients with primary central nervous system lymphoma (PCNSL) consists of two phases: induction, currently represented by a high-dose-methotrexate-based polychemotherapy, and consolidation. The optimal consolidation therapy has not been defined yet, but several strategies, such as whole-brain radiotherapy (WBRT), high-dose chemotherapy supported by autologous stem cell transplantation (HDC/ASCT) or nonmyeloablative chemotherapy, have been addressed in important randomized trials. Areas covered: This review provides an overview of the current role of consolidation strategies in young and fit patients with newly diagnosed PCNSL. Publications in English language, peer-reviewed, from high-quality international journals, edited from 2003 to 2021 were identified on PubMed. Expert opinion: Consolidation treatment significantly improved outcomes of PCNSL. Radiotherapy had represented for years the only choice in the consolidation therapy, but large randomized trials have demonstrated that HDC/ASCT is equally effective and associated with lower neurotoxicity risk in patients younger than 65-70 years. Encouraging results have been obtained using reduced-dose WBRT, while a recent randomized trial failed to demonstrate that consolidation with nonmyeloablative chemotherapy is more effective than HDC/ASCT in PCNSL patients. A personalized consolidation treatment, driven also by a response prediction model based on radiological and molecular details, may improve the management of PCNSL patients.
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Central Nervous System/pathology ; Central Nervous System Neoplasms/diagnosis ; Central Nervous System Neoplasms/therapy ; Combined Modality Therapy ; Hematopoietic Stem Cell Transplantation/methods ; Humans ; Lymphoma/drug therapy ; Lymphoma/therapy ; Methotrexate/therapeutic use ; Transplantation, Autologous
Chemical Substances	Methotrexate (YL5FZ2Y5U1)
Language	English
Publishing date	2022-01-12
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2516804-6
ISSN	1747-4094 ; 1747-4086
ISSN (online)	1747-4094
ISSN	1747-4086
DOI	10.1080/17474086.2022.2018297
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Article: High-Risk Neutropenic Fever and Invasive Fungal Diseases in Patients with Hematological Malignancies.

Microorganisms

2024 Volume 12, Issue 1

Abstract: Invasive fungal diseases (IFDs) still represent a relevant cause of mortality in patients affected by hematological malignancies, especially acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) undergoing remission induction chemotherapy, and ...

Abstract	Invasive fungal diseases (IFDs) still represent a relevant cause of mortality in patients affected by hematological malignancies, especially acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) undergoing remission induction chemotherapy, and in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Mold-active antifungal prophylaxis (MAP) has been established as a standard of care. However, breakthrough IFDs (b-IFDs) have emerged as a significant issue, particularly invasive aspergillosis and non-
Language	English
Publishing date	2024-01-06
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms12010117
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Article ; Online: Imaging biomarkers of leukaemic choroidopathy.

Menean, Matteo / Apuzzo, Aurelio / Mastaglio, Sara / Bernardi, Massimo / Ciceri, Fabio / Modorati, Giulio / Miserocchi, Elisabetta / Bandello, Francesco / Cicinelli, Maria Vittoria

Acta ophthalmologica

2023 Volume 101, Issue 5, Page(s) 553–559

Abstract: Purpose: To longitudinally investigate choroidal and choriocapillaris perfusion metrics and the number of choroidal hyperreflective foci (HRF) in patients with acute leukaemia (AL) before and after disease remission and to correlate these metrics with ... ...

Abstract	Purpose: To longitudinally investigate choroidal and choriocapillaris perfusion metrics and the number of choroidal hyperreflective foci (HRF) in patients with acute leukaemia (AL) before and after disease remission and to correlate these metrics with systemic parameters during active disease. Methods: Prospective, longitudinal study of 26 eyes of 14 AL patients. All patients underwent optical coherence tomography (OCT) and OCT-angiography (OCTA) in the acute phase. Subfoveal choroidal thickness (CT), total, luminal and stromal choroidal area (TCA, LCA, SCA), choroidal vascularity index (CVI), choriocapillaris flow deficits (cFD) density, and choroidal HRF number were computed. In a subset, the measurements were repeated after AL remission. Age- and gender-matched 26 healthy controls were recruited for cross-sectional comparisons. Results: Patient's mean age was 59 ± 12 years. The TCA, LCA, SCA and choroidal HRF number were significantly higher in patients than controls (p = 0.028, p = 0.044, p = 0.024 and p = 0.001, respectively). Lower haemoglobin levels were associated with lower CT (r = 0.58, p = 0.008). Higher D-dimer values were associated with lower TCA (r = -0.52, p = 0.008), lower LCA (r = -0.50, p = 0.006), higher cFD density (r = 0.41, p = 0.044) and higher choroidal HRF number (r = 0.47, p = 0.008). The CT, TCA, SCA and choroidal HRF number significantly reduced after AL remission (p = 0.001, p = 0.047, p = 0.007 and p = 0.002 respectively). The CVI increased significantly compared to the active phase (p = 0.013). Conclusion: The study demonstrates a subclinical choroidal involvement in patients with AL, with relative stromal thickening in the acute phase, and normalization after disease remission. Choroidal HRF were identified as a biomarker of leukaemic choroidopathy. Choriocapillaris and choroidal vascularity were inversely correlated with a systemic pro-coagulant state.
MeSH term(s)	Humans ; Middle Aged ; Aged ; Prospective Studies ; Cross-Sectional Studies ; Longitudinal Studies ; Choroid ; Angiography ; Tomography, Optical Coherence/methods ; Acute Disease
Language	English
Publishing date	2023-01-26
Publishing country	England
Document type	Journal Article
ZDB-ID	2408333-1
ISSN	1755-3768 ; 1755-375X
ISSN (online)	1755-3768
ISSN	1755-375X
DOI	10.1111/aos.15637
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Article ; Online: Neutralizing monoclonal antibodies for early treatment of hospital-acquired SARS-CoV-2 infection in hematologic patients.

Bussini, Linda / Testi, Diletta / Tazza, Beatrice / Oltolini, Chiara / Mastaglio, Sara / Sepulcri, Chiara / Campoli, Caterina / Trapani, Filippo / Pasquini, Zeno / Zappulo, Emanuela / Bassetti, Matteo / Viale, Pierluigi / Mikulska, Malgorzata / Bartoletti, Michele

EJHaem

2022

Abstract: Efficacy of early treatment with anti-SARS-CoV-2 spike protein monoclonal antibodies (mAbs ... for nosocomial SARS-CoV-2 infection in hematologic patients is unknown. Retrospective, cohort study conducted ... acquired SARS-CoV-2 infection diagnosed between November 2020 and December 2021. The principal exposure ...

Abstract	Efficacy of early treatment with anti-SARS-CoV-2 spike protein monoclonal antibodies (mAbs) for nosocomial SARS-CoV-2 infection in hematologic patients is unknown. Retrospective, cohort study conducted in four Italian teaching hospitals. We included adult patients with hematologic malignancies and hospital-acquired SARS-CoV-2 infection diagnosed between November 2020 and December 2021. The principal exposure variable was administration of mAbs. The primary endpoint was clinical failure dea composite outcome of mortality and/or invasive and noninvasive ventilation within 90 days from infection onset. We included 52 patients with hospital-acquired SARS-CoV-2 infection. Males were 29 (60%), median age was 62 (interquartile range [IQR] 48-70). Forty-five (86%) patients were on chemotherapy or had received chemotherapy within 30 days. MAbs were administered in 19/52 (36%) patients. Clinical failure occurred in 22 (42%) patients; 21% (4/19) in mAbs group versus 54% (18/33) in non-mAbs group (
Language	English
Publishing date	2022-09-02
Publishing country	United States
Document type	Journal Article
ISSN	2688-6146
ISSN (online)	2688-6146
DOI	10.1002/jha2.554
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Article: Case report: Intravitreal methotrexate in intraocular acute lymphoblastic leukemia.

Pederzolli, Matteo / Giglio, Fabio / Cicinelli, Maria Vittoria / Marchese, Alessandro / Modorati, Giulio / Mastaglio, Sara / Ciceri, Fabio / Bandello, Francesco / Miserocchi, Elisabetta

Frontiers in oncology

2022 Volume 12, Page(s) 951362

Abstract: Direct leukemic infiltration of the eye is most frequently associated with acute lymphoblastic leukemia (ALL), probably due to its well-known central nervous system (CNS) tropism. Systemic treatment alone may not be sufficient for intraocular leukemia. ... ...

Abstract	Direct leukemic infiltration of the eye is most frequently associated with acute lymphoblastic leukemia (ALL), probably due to its well-known central nervous system (CNS) tropism. Systemic treatment alone may not be sufficient for intraocular leukemia. Data on local treatment are scarce. Here, we present two cases of intraocular ALL treated with intravitreal methotrexate (MTX). Initially, anatomical improvement and visual stability were observed. The first patient experienced anatomical and visual worsening after a year of treatment. Treatment was withheld after 2 months for the second patient due to poor systemic conditions. Corneal toxicity and intraocular pressure elevation were observed in the first case. In both cases, eye involvement was associated with CNS or systemic relapse. This highlights the importance of incorporating ocular disease management in a comprehensive approach to therapy. Our experience corroborates previous findings on MTX injections as an effective and safe therapeutic option for intraocular leukemia. Further evidence is needed to consolidate the use of intravitreal MTX to treat such a debilitating localization of leukemia.
Language	English
Publishing date	2022-08-29
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.951362
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Article ; Online: RETINAL MICROVASCULAR CHANGES IN PATIENTS WITH ACUTE LEUKEMIA.

Cicinelli, Maria V / Mastaglio, Sara / Menean, Matteo / Marchese, Alessandro / Miserocchi, Elisabetta / Modorati, Giulio / Bernardi, Massimo / Ciceri, Fabio / Bandello, Francesco

Retina (Philadelphia, Pa.)

2022 Volume 42, Issue 9, Page(s) 1762–1771

Abstract: Purpose: To evaluate the retinal circulation in patients with active acute leukemia, to correlate the perfusion metrics with systemic laboratory values, and to assess the vascular perfusion after leukemia remission.: Methods: Longitudinal study of 22 ...

Abstract	Purpose: To evaluate the retinal circulation in patients with active acute leukemia, to correlate the perfusion metrics with systemic laboratory values, and to assess the vascular perfusion after leukemia remission. Methods: Longitudinal study of 22 eyes from 12 patients with acute leukemia; healthy eyes were recruited as control subjects. All patients underwent optical coherence tomography angiography at baseline. Optical coherence tomography angiography was repeated in case of morphologic leukemia remission. Results: Patients' age ranged from 37 to 74 years. All participants had a 20/20 vision. In all leukemic eyes, optical coherence tomography angiography detected vascular alterations in the macula and the peripapillary region. Vessel density values in the superficial capillary plexus were lower in patients with leukemia than control subjects (46.8 ± 3.6 vs. 49.2 ± 2%, P = 0.08), irrespective of the presence of leukemic retinopathy (7 eyes, 32%). Lower vessel density was associated with lower white blood cells ( P = 0.09) and lower platelets ( P = 0.001). Reappearance of small capillaries, increase in vessel density, reduction in vessel diameter, and increase in fractal dimension were seen after remission. Conclusion: Subclinical, reversible reduction in vessel density and complexity on optical coherence tomography angiography occurs in patients with active acute leukemia and is presumably associated with bone marrow function failure. Further studies are warranted to explore its functional and prognostic significance.
MeSH term(s)	Adult ; Aged ; Capillaries ; Fluorescein Angiography/methods ; Humans ; Leukemia ; Longitudinal Studies ; Macula Lutea/blood supply ; Middle Aged ; Retinal Vessels ; Tomography, Optical Coherence/methods
Language	English
Publishing date	2022-04-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	603192-4
ISSN	1539-2864 ; 0275-004X
ISSN (online)	1539-2864
ISSN	0275-004X
DOI	10.1097/IAE.0000000000003504
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Article: MRD in Venetoclax-Based Treatment for AML: Does it Really Matter?

Bernardi, Massimo / Ferrara, Felicetto / Carrabba, Matteo Giovanni / Mastaglio, Sara / Lorentino, Francesca / Vago, Luca / Ciceri, Fabio

Frontiers in oncology

2022 Volume 12, Page(s) 890871

Abstract: The prognosis of newly diagnosed patients with acute myeloid leukemia is still unfavorable in the majority of cases within the intermediate and mainly adverse genetic risk group but also in a considerable fraction of favorable-risk patients, mainly due ... ...

Abstract	The prognosis of newly diagnosed patients with acute myeloid leukemia is still unfavorable in the majority of cases within the intermediate and mainly adverse genetic risk group but also in a considerable fraction of favorable-risk patients, mainly due to recurrence of disease after complete remission achievement or, less frequently, primary refractoriness. Besides genetic classification at diagnosis, post-treatment prognostic factors include measurable residual disease evaluation in patients in complete remission and in most cases measurable residual disease (MRD) positivity predicts hematologic relapse potentially allowing early therapeutic intervention. Currently, the most commonly used methods for detection of minimal residual disease are multiparameter flow cytometry and quantitative PCR, applicable to around 90% and 50% of patients, respectively. In addition, in > 90% of acute myeloid leukemia (AML) patients, molecular aberrations can be identified by next-generation sequencing, a technology that is widely used in clinical practice for the initial mutational screening at the time of diagnosis but more often, for MRD detection because its flexibility allows almost every mutated gene to be used as an MRD marker. Threshold levels of residual disease and correlation with outcome have been thoroughly studied and established in younger patients treated with intensive induction and consolidation chemotherapy as well as after allogeneic transplantation. Yet, experience on MRD monitoring and interpretation in patients treated with low-intensity regimens, including new agents, is still limited. The updated armamentarium of anti-leukemic agents includes the BCL-2 inhibitor venetoclax, which demonstrated good tolerability, high response rates, and prolonged overall survival when combined with hypomethylating agents or low dose cytarabine in patients considered elderly/"unfit" to tolerate intensive regimens. Although remissions with negative minimal residual disease clearly translated into improved outcomes after intensive treatments, data supporting the same evidence in patients receiving low-intensity venetoclax-based treatments are not still consolidated. We here review and discuss more recent data on the minimal residual disease interpretation and role in AML patients treated with venetoclax-based combinations.
Language	English
Publishing date	2022-07-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.890871
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Article: Defibrotide Prophylaxis of Sinusoidal Obstruction Syndrome in Adults Treated With Inotuzumab Ozogamicin Prior to Hematopoietic Stem Cell Transplantation.

Giglio, Fabio / Xue, Elisabetta / Greco, Raffaella / Lazzari, Lorenzo / Clerici, Daniela Teresa / Lorentino, Francesca / Mastaglio, Sara / Marktel, Sarah / Lupo-Stanghellini, Maria Teresa / Marcatti, Magda / Corti, Consuelo / Bernardi, Massimo / Piemontese, Simona / Ciceri, Fabio / Peccatori, Jacopo

Frontiers in oncology

2022 Volume 12, Page(s) 933317

Abstract: Sinusoidal Obstruction Syndrome (SOS) is a life threatening HSCT complication and it can rapidly evolve in Multiple Organ Dysfunction Syndrome, with a mortality exceeding 80%. Early treatment with defibrotide is the leading factor for efficacy. Its ... ...

Abstract	Sinusoidal Obstruction Syndrome (SOS) is a life threatening HSCT complication and it can rapidly evolve in Multiple Organ Dysfunction Syndrome, with a mortality exceeding 80%. Early treatment with defibrotide is the leading factor for efficacy. Its prophylactic use is recommended in the pediatric setting, but its value isn't validated for adults, although factors for individual risk assessment are debated. We here present a real-world experience of Defibrotide prophylaxis in adults at very high risk of SOS. We treated with prophylactic Defibrotide and Ursodeoxycholic Acid seven patients receiving allogeneic HSCT for high risk B-ALL, previously treated with single agent Inotuzomab-Ozogamicin. They all had other high risk factors for SOS such as previous hepatotoxicity, previous allo-HSCT, double alkylating conditioning. All patients received Treosulfan-Fludarabine conditioning, Thiotepa was added in 4 patients and 4GyTBI in 2 patients. GvHD prophylaxis included post-transplant cyclophosphamide, rapamycin and mycophenolate. Donor source was PBSC. Five patients received family MMRD transplant, 1 patient a MRD transplant and 1 patient a MUD transplant. Non-severe gastrointestinal bleeding occurred in two patients requiring defibrotide temporarily discontinuation. SOS occurred in 3/7 cases within 21 days after HSCT and no late-onset SOS were diagnosed. SOS caused death in all cases. All three patients were characterized by a common pattern of very high risk factors by prior HSCT, they all received a myeloablative conditioning with Treosulfan-Thiotepa and a MMRD transplant. Defibrotide prophylaxis apparently failed to protect against the development of SOS in those patients treated with a double alkylator-based conditioning regimen, while a possible efficacy for the other high-risk patients is debatable.
Language	English
Publishing date	2022-06-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.933317
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Article ; Online: Minnesota acute graft-

Ardizzoia, Federica / Lorentino, Francesca / Bruno, Alessandro / Marktel, Sarah / Giglio, Fabio / Clerici, Daniela / Farina, Francesca / Mastaglio, Sara / Piemontese, Simona / Assanelli, Andrea A / Carrabba, Matteo G / Bernardi, Massimo / Corti, Consuelo / Peccatori, Jacopo / Ciceri, Fabio / Greco, Raffaella / Lupo-Stanghellini, Maria Teresa

Haematologica

2022 Volume 107, Issue 11, Page(s) 2748–2751

MeSH term(s)	Humans ; Graft vs Host Disease/prevention & control ; Minnesota ; Cyclophosphamide/therapeutic use ; Hematopoietic Stem Cell Transplantation ; Risk Factors
Chemical Substances	Cyclophosphamide (8N3DW7272P)
Language	English
Publishing date	2022-11-01
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.2022.281269
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Article ; Online: Second Solid Cancers After Hematopoietic Stem Cell Transplantation: Active Surveillance During Long-term Follow-up.

Lupo-Stanghellini, Maria Teresa / Piemontese, Simona / Assanelli, Andrea / Serpenti, Fabio / Mastaglio, Sara / Clerici, Daniela / Giglio, Fabio / Greco, Raffaella / Lorentino, Francesca / Pavesi, Francesca / Farina, Francesca / Marktel, Sarah / Corti, Consuelo / Peccatori, Jacopo / Ciceri, Fabio

HemaSphere

2021 Volume 5, Issue 11, Page(s) e654

Language	English
Publishing date	2021-10-28
Publishing country	United States
Document type	Journal Article
ISSN	2572-9241
ISSN (online)	2572-9241
DOI	10.1097/HS9.0000000000000654
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