Background—Allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients are subject to major risks for bacterial bloodstream infections (BSIs), including emergent multidrug-resistant (MDR) organisms, which still represent the main cause of morbidity and mortality in transplanted patients. Methods: We performed an observational, retrospective, single-center study on patients undergoing allo-HSCT between 2004 and 2020 at the Stem Cell Transplant Unit in Turin to assess the incidence, etiology, and outcomes of BSIs and to explore any risk factors for bacteriaemia. Results: We observed a total of 178 bacterial BSIs in our cohort of 563 patients, resulting in a cumulative incidence of 19.4%, 23.8%, and 28.7% at 30, 100, and 365 days, respectively. Among isolated bacteria, 50.6% were Gram positive (GPB), 41.6% were Gram negative (GNB), and 7.9% were polymicrobial infections. Moreover, BSI occurrence significantly influenced 1-year overall survival. High and very high Disease Risk Index (DRI), an haploidentical donor, and antibacterial prophylaxis were found as results as independent risk factors for bacterial BSI occurrence in multivariate analysis. Conclusions: In our experience, GNB have overwhelmed GPB, and fluoroquinolone prophylaxis has contributed to the emergence of MDR pathogens. Local resistance patterns and patients’ characteristics should therefore be considered for better management of bacteremia in patients receiving an allogeneic HSCT.

Acute myeloid leukemia (AML) in older patients is characterized by unfavorable prognosis due to adverse disease features and a high rate of treatment-related complications. Classical therapeutic options range from intensive chemotherapy in fit patients, potentially followed by allogeneic hematopoietic cell transplantation (allo-HCT), to hypomethylating agents or palliative care alone for unfit/frail ones. In the era of precision medicine, the treatment paradigm of AML is rapidly changing. On the one hand, a plethora of new targeted drugs with good tolerability profiles are becoming available, offering the possibility to achieve a prolonged remission to many patients not otherwise eligible for more intensive therapies. On the other hand, better tools to assess patients’ fitness and improvements in the selection and management of those undergoing allo-HCT will hopefully reduce treatment-related mortality and complications. Importantly, a detailed genetic characterization of AML has become of paramount importance to choose the best therapeutic option in both intensively treated and unfit patients. Finally, improving supportive care and quality of life is of major importance in this age group, especially for the minority of patients that are still candidates for palliative care because of very poor clinical conditions or unwillingness to receive active treatments. In the present review, we discuss the evolving approaches in the treatment of older AML patients, which is becoming increasingly challenging following the advent of new effective drugs for a very heterogeneous and complex population.

In the last decade, anti-CD19 CAR-T cell therapy has led to a treatment paradigm shift for B-cell non-Hodgkin lymphomas, first with the approval for relapsed/refractory (R/R) large B-cell lymphomas and subsequently for R/R mantle cell and follicular lymphoma. Many efforts are continuously being made to extend the therapeutic setting in the lymphoma field. Several reports are supporting the safety and efficacy of CAR-T cells in patients with central nervous system disease involvement. Anti-CD30 CAR-T cells for the treatment of Hodgkin lymphoma are in development and early studies looking for the optimal target for T-cell malignancies are ongoing. Anti-CD19/CD20 and CD19/CD22 dual targeting CAR-T cells are under investigation in order to increase anti-lymphoma activity and overcome tumor immune escape. Allogeneic CAR product engineering is on the way, representing a rapidly accessible ‘off-the-shelf’ and potentially more fit product. In the present manuscript, we will focus on recent advances in CAR-T cell therapy for lymphomas, including new settings and future perspectives in the field, reviewing data reported in literature in the last decade up to October 2023.

Background: Accurate assessment of elderly acute myeloid leukemia (AML) patients is essential before intensive induction chemotherapy and subsequent allogeneic hematopoietic stem cell transplantation. In this context, we investigated the capacity of three scores for frailty prediction. Methods: At diagnosis, 197 patients were clinically evaluated for appropriate treatment intensity. In parallel and independently, the G8-score, the Hematopoietic Stem Cell Index (HCT-CI) and the AML-score for CR were determined for each patient and analyzed with respect to overall survival (OS). Results: The G8-score and the HCT-CI were able to significantly separate “fit” from “unfit” patients, <0.001 and p = 0.008. In univariate Cox models, the predictive role for OS was confirmed: for the G8-score (HR: 2.35, 95% CI 1.53–3.60, p < 0.001), the HCT-CI (HR: 1.91, 95% CI 1.17–3.11, p = 0.009) and the AML-score (HR: 5.59, 95% CI 2.04–15.31, p = 0.001), the latter was subsequently used to verify the cohort. In the multivariate Cox model, the results were confirmed for the G8- (HR: 2.03, p < 0.001) and AML-score (HR: 3.27, p = 0.001). Of interest, when combining the scores, their prediction capacity was significantly enhanced, p < 0.001. Conclusions: The G8-, the HCTCI and the AML-score represent valid tools in the frailty assessment of elderly AML patients at diagnosis.

In the last few decades, chimeric antigen receptor (CAR) T-cell therapy has led to a paradigm shift in the treatment of hematological malignancies, including various subtypes of B-cell non-Hodgkin’s lymphoma, B-cell acute lymphoblastic leukemia, and multiple myeloma. However, most patients experience refractoriness to CAR T-cells or relapse after treatment. Many efforts are underway to understand the mechanisms behind CAR T-cell failure, which are mainly related to CAR T-cell dysfunction, tumor-intrinsic resistance, an immunosuppressive tumor microenvironment, manufacturing issues, or patient-related factors. Several strategies are being developed to overcome these resistance mechanisms, including the engineering of more functional allogeneic CAR T-cell products, the targeting of alternative tumor antigens, and combination therapies with other drugs such as checkpoint inhibitors or small molecules to enhance CAR T-cell efficacy. In this review, we will provide an updated overview of the mechanisms of CAR T-cell failure and the therapeutic advances currently under development to address them.