Publications by authors named "Luana Schiattone"

11 Publications

  • Page 1 of 1

Pre-existing and treatment-emergent autoimmune cytopenias in patients with CLL treated with targeted drugs.

Blood 2021 Mar 2. Epub 2021 Mar 2.

University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.

Autoimmune cytopenias (AIC) affect 5-9% of patients with chronic lymphocytic leukemia (CLL). Targeted drugs - ibrutinib, idelalisib and venetoclax - have a prominent role in the treatment of CLL, but their impact on CLL-associated AIC is largely unknown. In this study, we evaluated the characteristics and outcome of pre-existing AIC, and described the incidence, quality and management of treatment-emergent AIC during therapy with targeted drugs in patients with CLL. We collected data from 572 patients treated with ibrutinib (9% in combination with an anti-CD20 monoclonal antibody), 143 treated with idelalisib-rituximab and 100 treated with venetoclax (12% in combination with an anti-CD20 monoclonal antibody). A history of pre-existing AIC was reported in 104/815 patients (13%). Interestingly, 80% of patients whose AIC was not resolved at the time of targeted drug start experienced an improvement or a resolution during therapy. Treatment-emergent AIC occurred in 1% of patients during ibrutinib therapy, in 0.9% during idelalisib and in 7% during venetoclax, with an estimated incidence rate of 5, 6 and 69 episodes per 1000 patients per year of exposure in the three treatment groups, respectively. The vast majority of patients who developed treatment-emergent AIC carried unfavorable biological features such as an unmutated IGHV, and a del(17p) and/or TP53 mutation. Notably, despite AIC, 83% of patients were able to continue the targeted drug, in some cases in combination with additional immunosuppressive agents. Overall, treatment with ibrutinib, idelalisib and venetoclax appears to have a beneficial impact on CLL-associated AIC, inducing an improvement or even a resolution of pre-existing AIC in most cases and eliciting treatment-emergent AIC in a negligible portion of patients.
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http://dx.doi.org/10.1182/blood.2020008201DOI Listing
March 2021

Prognostic impact of tumor-associated macrophages, lymphocyte-to-monocyte and neutrophil-to-lymphocyte ratio in diffuse large B-cell lymphoma.

Am J Blood Res 2020 25;10(4):97-108. Epub 2020 Aug 25.

Unit of Pathology, Department of Medical Biotechnologies, University of Siena Siena, Italy.

Introduction: Microenvironment has a prognostic influence in diffuse large B-cell lymphoma (DLBCL); among its components, tumor-associated macrophages (TAM) play a leading role. TAM can be classified into M1 (anti-tumor) and M2 (pro-tumor). Another prognostic factor could be represented by lymphocyte-to-monocyte and neutrophil-to-lymphocyte ratio (LMR and NLR).

Objective: The aim of the study is to evaluate the prognostic impact of M1 and M2 TAM subtypes, LMR and NLR in DLBCL.

Methods: We analyzed 37 consecutive patients between 2009 and 2013. Out of 37 patients, 28/37 (75.6%) received R-CHOP/CHOP-like regimens, 9/37 (24.4%) less intensive therapies. Immunohistochemistry was performed with antibodies against CD68 and CD163. We divided our cohort into 2 categories according to the Steidl score. TAM who coexpressed CD68 and CD163 were considered as M2. For LMR and NLR we used previously published cut-offs of 2.71 and 2.81.

Results: CR rate was 70.3%; we did not record a significant correlation between CD68+ TAM, CD163+ TAM, CD68+/CD163+ TAM, LMR, NLR and CR. We observed a reduced PFS in patients with IPI ≥ 2 and high M2 TAM expression and a trend between higher expression of CD68+ TAM and improved PFS.

Conclusion: M2 TAM could have a prognostic role for IPI ≥ 2 DLBCL patients receiving R-CHOP, which thus warrants further investigation.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486489PMC
August 2020

The evolving treatment landscape of chronic lymphocytic leukemia.

Curr Opin Oncol 2019 11;31(6):568-573

Strategic Research Program on CLL, IRCCS Ospedale San Raffaele.

Purpose Of Review: This review provides guidance in the rapidly changing scenario of chronic lymphocytic leukemia (CLL) treatment. New studies as well as updates of other seminal ones have been recently presented and are likely to change the management of patients with CLL in everyday clinical practice.

Recent Findings: Kinase inhibitors (e.g. ibrutinib and idelalisib) have transformed the treatment paradigm in CLL in both front-line and relapsed/refractory patients. Longer follow-up data are now available supporting the safety of ibrutinib and the continuous administration required per current label. Novel studies show the superiority of the drug alone or in combination with monoclonal antibodies compared with standard chemoimmunotherapy. The combination of venetoclax and obinutuzumab (treatment-naïve, only in United States) or rituximab (relapsed/refractory) has granted approval from the regulatory authorities in United States and Europe, based on phase 3 randomized studies. These novel chemo-free combinations allow for fixed-duration treatment and undetectable minimal residual disease. Novel targeted strategies including second and third generation BTK and PI3K inhibitors are currently under investigation and promise to further improve the CLL treatment armamentarium. The chimeric-antigen receptor (CAR) T cells are coming to the stage with promising efficacy and new challenges.

Summary: A bright chemo-free era for CLL patients is just around the corner. A deep knowledge of currently available evidences is key to tailor treatment choice and optimize long-term tolerability and disease control. Fixed-duration combinations are investigated to allow treatment holidays and avoid the emergence of resistant clones under the selective pressure of continuous treatment.
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http://dx.doi.org/10.1097/CCO.0000000000000585DOI Listing
November 2019

Efficacy and safety of rituximab plus bendamustine for gastric marginal zone lymphoma.

Leuk Lymphoma 2019 03 20;60(3):833-835. Epub 2018 Sep 20.

a Unit of Hematology , Azienda Ospedaliera Universitaria Senese , Siena , Italy.

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http://dx.doi.org/10.1080/10428194.2018.1504938DOI Listing
March 2019

Primary CNS lymphoma: latest updates and a 10-year monocenter experience.

Blood Res 2018 Jun 25;53(2):174-177. Epub 2018 Jun 25.

Unit of Hematology, Azienda Ospedaliera Universitaria Senese and University of Siena, Siena, Italy.

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http://dx.doi.org/10.5045/br.2018.53.2.174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021563PMC
June 2018

Durable response after VNCOP-B and rituximab in an elderly patient with high-grade B-cell lymphoma.

Acta Clin Belg 2018 Dec 6;73(6):408-412. Epub 2017 Dec 6.

a Unit of Hematology , Azienda Ospedaliera Universitaria Senese , Siena , Italy.

Objectives And Methods:  High-grade B-cell lymphoma, NOS (HGBL) have an aggressive clinical behavior and poor outcome using regimens currently employed for diffuse large B-cell lymphoma (DLBCL) such as rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Promising results have been reported with more intensive regimens but this strategy is not suitable for elderly or unfit patients. Rituximab in association with cyclophosphamide, mitoxantrone, vincristine, etoposide, bleomycin, and prednisone (R-VNCOP-B) demonstrated high efficacy and manageable toxicity as first-line treatment for elderly aggressive non-Hodgkin lymphoma patients.

Results And Conclusion: In this case study, we report the rapid improvement, long-lasting complete remission, and mild toxicity of R-VNCOP-B regimen in an elderly, triple-expressor HGBL patient, with aggressive disease and poor-risk profile.
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http://dx.doi.org/10.1080/17843286.2017.1412888DOI Listing
December 2018

Therapeutic Use of Brentuximab Vedotin in CD30+ Hematologic Malignancies.

Anticancer Agents Med Chem 2017 ;17(7):886-895

Division of Hematology, University of Siena, Siena, Italy.

The CD30 antigen is strongly expressed on neoplastic cells in classical Hodgkin lymphoma (HL), anaplastic large cell lymphoma (ALCL) and other hematologic malignancies (such as DLBCL and cutaneous TCL), while is almost undetectable on healthy tissues, representing an ideal immunotherapeutic target. Since unconjugated anti-CD30 antibody (SGN-30) demonstrated limited clinical activity, researchers' effort aimed to create an antibody-drug conjugate (ADC), leading to discovery of SGN-35 (brentuximab vedotin), in which an anti-CD30 antibody is linked to the antimitotic agent monomethyl auristatin E (MMAE). In the first phase I study in CD30+ hematologic malignancies (the majority of patients with HL), the maximum tolerated dose was fixed respectively at 1.8mg/Kg every 3 weeks, overall response rate (ORR) and complete response (CR) rate were 38% and 24%. In 2 subsequent phase II studies, amazing results were reported, that permitted accelerated FDA approval for relapsed/refractory patients and led to the development of many clinical trials including BV as first-line HL and ALCL treatment. Moreover, as CD30 antigen may be expressed by other malignancies, the potential therapeutic application is increasing, including at least diffuse large B-cell lymphoma, T-cell lymphomas other than ALCL and cutaneous lymphoproliferative disorders. BV is administrated as outpatient regimen and is usually well tolerated; sensorial peripheral neuropathy represents the most common toxic effect, although it is dose-dependent and at least partially reversible in most cases, after dose reduction and/or treatment ending.
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http://dx.doi.org/10.2174/1871520616666160902100506DOI Listing
August 2017

Radiotherapy with rituximab as first-line treatment for early-stage follicular lymphoma.

Leuk Lymphoma 2015 23;56(10):2997-8. Epub 2015 Mar 23.

a Unit of Hematology, University Hospital of Siena , Siena , Italy.

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http://dx.doi.org/10.3109/10428194.2015.1022768DOI Listing
April 2016

Low-dose chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab in follicular lymphoma.

Eur J Haematol 2015 Mar 13;94(3):277-8. Epub 2014 Sep 13.

Division of Haematology, University Hospital of Siena, Siena, Italy.

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http://dx.doi.org/10.1111/ejh.12428DOI Listing
March 2015

Chemoimmunotherapy with oral low-dose fludarabine, cyclophosphamide and rituximab (old-FCR) as treatment for elderly patients with chronic lymphocytic leukaemia.

Leuk Res 2014 Aug 2;38(8):891-5. Epub 2014 Jun 2.

Hematology, Azienda Ospedaliera Universitaria, Siena, Italy.

Median age at diagnosis for chronic lymphocytic leukaemia (CLL) patients is now 72 years, thus a consistent number of patients may not tolerate standard doses i.v. of fludarabine, cyclophosphamide and rituximab (FCR), the best available therapy, due to unacceptable myelotoxicity and risk of severe infections. We studied safety and efficacy of the addition of rituximab to the oral low-dose FC regimen (old-FCR) in a selected population of 30 elderly (median age 75, 15 untreated, 15 treated with 1 prior therapy) CLL patients. Complete remission (CR) rate was 80% in the untreated patients (overall response rate, ORR 93%), and 30% in pretreated patients (ORR 74%). Progression free survivals (PFS) were 45 months and 30 months in the untreated and treated patients, respectively. In patients achieving CR, old-FCR led to PFS of 67 months. Moreover, haematological toxicity was mild (grade 3-4: 15%) and patients were treated mostly in outpatient clinic. Old-FCR could be a good therapy option for elderly CLL patients outside clinical trials, larger studies are needed to confirm our findings.
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http://dx.doi.org/10.1016/j.leukres.2014.05.016DOI Listing
August 2014