The Treatment of Burkitt Lymphoma With the Berlin-Frankfurt-Münster Protocol With Rituximab and Consolidative Autologous Transplantation.

INTRODUCTION: Intensive treatment approaches are required for adult patients with Burkitt lymphoma (BL), although an univocal standard of care still does not exist. The use of frontline autologous stem cells transplantation (ASCT) is debated. PATIENTS AND METHODS: Between 2004 and 2020, 50 patients with BL were treated with the Berlin-Frankfurt-Münster (BFM). Treatment plan consisted of 3 blocks, A (ifosfamide, vincristine, methotrexate, etoposide, and cytarabine), B (vincristine, cyclophosphamide, methotrexate, and doxorubicin), and C (vindesine, methotrexate, etoposide, and cytarabine), each repeated twice, every 28 days. Rituximab was given at day 1 each block. Intrathecal prophylaxis was given once per each block. ASCT was scheduled at the end of the 6 blocks after conditioning. RESULTS: Median age at onset was 38 years (range 16-72); stages III-IV disease was observed in 82% of cases; bulky disease occurred in 44% of the patients, with B-symptoms in 38%. Stem cell harvest was performed in 72% of patients, who all received a subsequent ASCT. The full 6 blocks treatment was completed in 70% of the patients. The overall response rate was 74%, with a complete response rate of 60%. Ten-year overall survival and progression-free survival were 83.7% and 76.0%, respectively, without reaching the median. Ten-year disease-free survival was 80.3%. Grades 3-4 neutropenia, thrombocytopenia, anemia, and mucositis were seen in 96%, 60%, 32%, and 24% of patients. Infections occurred in 60% of patients. CONCLUSION: Intensive treatment according to BFM protocol, with rituximab and ASCT, appears feasible, safe, and highly effective in adult patients with BL, as confirmed by long-term survival rates reflecting response maintenance.

Diffuse large B cell lymphoma characteristics and outcomes during the COVID-19 pandemic in two tertiary centers - an Israeli/ Italian study.

The COVID-19 pandemic posed a major challenge in cancer care worldwide which might have an impact on the management of diffuse large B-cell lymphoma (DLBCL). We conducted a retrospective study comparing characteristics, management, and outcomes of DLBCL patients diagnosed during the first year of the COVID-19 pandemic (1/3/2020-28/2/2021) to those diagnosed in the previous year (1/3/2019-28/2/2020) in two tertiary centers in Italy and Israel. 182 patients were diagnosed with DLBCL during the study period. More patients were diagnosed during the pandemic compared to the year before: 60 vs. 29 and 54 vs. 39 in Italy and in Israel, respectively. Trends towards older age and higher transformation rates were shown during the pandemic. The interval between the initiation of symptoms and diagnosis was longer during the pandemic. Five and four patients were diagnosed with COVID-19 during treatment in Italy and in Israel, respectively. there was no difference in dose density and intensity of treatment, before and during the pandemic. The median follow-up during and before the pandemic was 15.2 and 25.5 months, respectively. Progression-free survival (PFS) was slightly shorter during the pandemic compared to the year before (64.9% vs. 70.6%; p = 0.0499). In multivariate analysis, older age and transformed disease were independently related to PFS, while diagnosis of DLBCL during the pandemic was not. Despite the challenges caused by COVID-19 pandemic, the management of DLBCL patients remained unchanged including dose density and intensity. Nevertheless, a shorter PFS during the outbreak might be attributed to differences in patients' characteristics.

Economic evaluation of anti-CD19 CAR T-cell pathway for large B-cell lymphomas in the real-life setting: the experience of an Italian hub center in the first three years of activity.

Poor literature report actual and detailed costs of chimeric antigen receptor (CAR) T-cell pathway in a real-life setting. We retrospectively collect data for all patients with relapsed/refractory aggressive large B-cell lymphoma who underwent leukapheresis between August 2019 and August 2022. All costs and medical resource consumption accountability were calculated on an intention-to-treat (ITT) basis, starting from leukapheresis to the time when the patient (infused or not) exited the CAR T-cell pathway for any reason. Eighty patients were addressed to leukapheresis and 59 were finally infused. After excluding CAR-T product cost, the main driver of higher costs were hospitalizations followed by the examinations/procedures and other drugs, respectively 43.9%, 26.3% and 25.4% of the total. Regarding costs of drugs and medications other than CAR T products, the most expensive items are those referred to AEs, both infective and extra-infective within 30 days from infusion, that account for 63% of the total. Density plot of cost analyses did not show any statistically significant difference with respect to the years of leukapheresis or infusion. To achieve finally 59/80 infused patients the per capita patients without CAR-T products results 74,000 euros. This analysis covers a growing concern on health systems, the burden of expenses related to CAR T-cell therapy, which appears to provide significant clinical benefit despite its high cost, thus making economic evaluations highly relevant. The relevance of this study should be also viewed in light of continuously evolving indications for this therapy.

Efficacy and Safety of Frontline Single-Agent Rituximab in Extranodal Marginal Zone Lymphoma.

First-line therapy for patients with extranodal marginal zone lymphoma (EMZL) is not well established, except for eradication therapy for Helicobacter pylori in early gastric MZL. Various regimens, for example, locoregional treatment and systemic chemo-immunotherapy, can be used depending on the site and stage of disease. Single-agent rituximab is a useful approach in the setting of localized, low-intermediate risk EMZL. The aim our research was to analyze the effectiveness and safety of single-agent rituximab (375 mg/m2 once weekly for 4 weeks) in naïve EMZL in a real-life setting. The primary endpoint was the overall response rate (ORR), secondary endpoints were progression-free (PFS), overall (OS) and disease-free survivals (DFS), and drug tolerability. Fifty-nine patients were analyzed. Median time between diagnosis and rituximab was 3.6 months. The ORR was 89.9%, with 67.8% complete response (CR). Median DFS and PFS were reached at 6.3 and 5.3 years, respectively. After a median follow-up of 5 years, median OS was not reached. The most common adverse event was infusion reaction, reported in 28 cases, mainly during the first infusion and easily manageable. Single-agent rituximab may represent a valid therapeutic option in the first-line treatment of EMZL, at least for localized disease, with a favorable toxicity profile.

Endobronchial Presentation of Hodgkin Lymphoma Responding to Pembrolizumab: A Case Report.

An endobronchial localization of Hodgkin lymphoma is rare, and few experiences since the 1900s have been reported in the literature. Here we report the first case of a relapsed/refractory Hodgkin lymphoma with a critical vegetative mass at the level of the trachea successfully treated with pembrolizumab.

Elderly Non-GCB Diffuse Large B-Cell Lymphoma Patient Responding to Lenalidomide after Epicardial Relapse: A Case Report.

There is an unmet clinical need for elderly or unfit diffuse large B-cell lymphoma (DLBCL) patients ineligible for autologous stem cell transplantation. Lenalidomide is an immunomodulatory agent with antitumor activity in non-Hodgkin lymphoma, with an acceptable toxicity profile and manageable side effects. A 79-year-old Caucasian male with non-germinal center B-cell-like DLBCL achieved complete remission (CR) after first-line treatment with seven out of eight scheduled cycles of a polychemotherapy containing anthracycline, which had to be discontinued early due to the onset of atrial fibrillation. After 5 months, the patient had an early epicardial relapse. He underwent lenalidomide considering age, cardiological comorbidities, and chronic renal failure. After the third cycle, he achieved CR, confirmed at restaging after the sixth cycle of treatment. Lenalidomide was safe and well tolerated in a patient with atrial fibrillation developed after an anthracycline-based regimen and a relapse of the DLBCL. Moreover, this regimen was effective in a case with a rare extranodal involvement of the epicardium.

Global outcomes and prognosis for relapsed/refractory mature T-cell and NK-cell lymphomas: Results from PETAL consortium.

Variances in global access to drugs and treatment practices make it challenging to understand the benefit of contemporary therapies in patients with relapsed and refractory (R/R) mature T-cell and NK-cell lymphomas (MTCL and MNKCL). We conducted an international retrospective cohort study of 925 patients with R/R MTCL and MNKCL. In PTCL-NOS and ALK- ALCL, patients with relapsed lymphoma demonstrated a superior median overall survival (OS) relative to refractory from the time of second-line treatment. We identified several independent predictors of OS for R/R lymphoma including age >60, primary refractory disease, histological subtype other than AITL, extranodal sites >1, Ki67 ≥40%, and absolute lymphocyte count

Prolonged responses to brentuximab vedotin as last therapy in Hodgkin lymphoma failing autologous transplantation: A case series.

The follow-up of the pivotal trial and large case series reports of a proportion of patients, between 5% and 9%, with relapsed or refractory Hodgkin lymphoma failing autologous stem cell transplantation and treated with brentuximab vedotin, achieving and maintaining long lasting complete responses with no further treatment. Very long-term data on the outcomes of such patients are indeed underreported. Our institutional experience with patients meeting these characteristics and in continuous complete response for more than 5 years after brentuximab vedotin was reviewed. Five patients achieved a median duration of complete response of 7.4 (range 5.1-8.1) years, and none of them encountered disease relapse or received any subsequent consolidation, including allogeneic transplantation. A proportion of patients failing autologous transplantation and receiving subsequent brentuximab vedotin may reach a long-lasting complete response with no need of further treatment. These patients are therefore considered cured. The role of allogeneic transplantation in such patients is matter of debate.

Escherichia coli J5: imunização de fêmeas bovinas leiteiras contra mastites causadas por Escherichia coli / Escherichia coli J5: immunization of dairy cows against Escherichia coli mastitis

Neste trabalho, revisamos os principais aspectos ligados à mastite causada por coliformes, mais especificamente a Escherichia coli, com enfoque principal nos fatores de risco associados ao animal, bem como na utilização da vacina Escherichia coli J5 na imunização de fêmeas bovinas leiteiras. Os coliformes estão amplamente distribuídos no ambiente, assumindo especial importância em sistemas de criação em que a busca pela qualidade do leite mantém a contagem de células somáticas (CCS) em níveis inferiores a 150000 células ml-1. Nesse contexto, o período seco representa um momento de extrema importância na definição da ausência ou não de um quadro de mastite, decorrente da ação de patógenos ambientais no pós-parto imediato. A terapia para vacas secas frente a infecções por germes ambientais perde eficácia, sendo necessária a associação a outros métodos, como, por exemplo, a vacinação com Escherichia coli J5. A cepa J5, por possuir um antígeno nuclear relativamente exposto, é capaz de estimular a produção de imunoglobulinas que apresentam reação cruzada com antígenos nucleares de outras bactérias, resultando em uma imunidade contra uma variedade de gêneros e cepas bacterianas. Estudos demonstram que a vacinação com Escherichia coli J5 é capaz de reduzir a ocorrência, intensidade e duração de casos clínicos de mastite por Escherichia coli, sendo também observada uma maior produção de leite nos animais vacinados. Entretanto, ainda é controverso seu papel na redução da CCS.

This paper aims to review the main aspects of coliform mastitis, specifically Escherichia coli, emphasizing the immunization of dairy cows with Escherichia coli J5 vaccine, as well as the animal risk factors. Coliforms are widespread in the environment and are of particular importance in farming systems in which the search for a greater milk quality guarantee low somatic cell counts (<150,000 cells ml-1). The dry period is an extremely important moment that plays crucial role in the occurrence of mastitis caused by environmental pathogens during the immediate postpartum. The dry cow therapy against environmental infections has lost effectiveness leading to the need for the combination with other methods such as immunization with Escherichia coli J5 vaccine. Due to a relatively exposed nuclear antigen, the Escherichia coli strain J5 can stimulate the production of immunoglobulins that cross-react with nuclear antigens from other bacteria. It results in immunity against a variety of bacterial genres and strains. It has been shown that the use of Escherichia coli J5 vaccine can reduce the occurrence, intensity and duration of clinical cases of Escherichia coli mastitis, besides increase the production of dairy cows. However, its role in reducing milk SCC is still controversial.