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.

Novelty in total body irradiation (TBI) as part of pre-transplant conditioning regimens lacked until recently, despite the developments in the field of allogeneic stem cell transplants. Long-term toxicities have been one of the major concerns associated with TBI in this setting, although the impact of TBI is not so easy to discriminate from that of chemotherapy, especially in the adult population. More recently, lower-intensity TBI and different approaches to irradiation (namely, total marrow irradiation, TMI, and total marrow and lymphoid irradiation, TMLI) were implemented to keep the benefits of irradiation and limit potential harm. TMI/TMLI is an alternative to TBI that delivers more selective irradiation, with healthy tissues being better spared and the control of the radiation dose delivery. In this review, we discussed the potential radiation-associated long-term toxicities and their management, summarized the evidence regarding the current indications of traditional TBI, and focused on the technological advances in radiotherapy that have resulted in the development of TMLI. Finally, considering the most recent published trials, we postulate how the role of radiotherapy in the setting of allografting might change in the future.

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.

Background/Objectives. Recent evidence underscores the prognostic and classificatory relevance of somatic mutations in myelodysplastic neoplasms (MDSs) and acute myeloid leukemia (AML). Methods. This prospective study assessed gene mutation dynamics via next-generation sequencing (NGS) in 84 MDS/AML patients treated with intensive chemotherapy or hypomethylating agents plus venetoclax. Results. At diagnosis, 95% had somatic mutations detected by NGS, while only 29% had a measurable residual disease (MRD) marker with qPCRs. NGS at complete remission (CR) was performed in 56/71 patients who achieved CR; 59% had persisting mutations, mostly in DNMT3A, TET2, and ASXL1 (DTA mutations). Mutations’ persistence in CR was linked to a shorter relapse-free survival (RFS; median 8 months vs. not reached, HR 4.41, 95% CI 1.69–11.49; p = 0.002) and overall survival (OS; 2-year OS: 51.5% vs. 88%, HR 4.02, 95% CI 1.39–11.65; p = 0.001). Combining NGS and multiparameter flow cytometry (MFC) for MRD detection, we divided patients into three groups with distinct RFS (NGS−/MFC−, NGS−/MFC+, or NGS+/MFC− and NGS+/MFC+), with double-negative patients displaying the best RFS (p < 0.001). In the multivariate analysis, NGS and MFC MRD+ were independent predictors of RFS. Conclusions. This real-world study confirms the added prognostic role of NGS in MRD detection on RFS, particularly when combined with MFC. This approach may improve risk stratification and guide treatment decisions.

Background: Despite the adoption of pediatric-like chemotherapy protocols, the introduction of new immunotherapies and a better understanding of the oncogenic landscape, the outcome for adult patients with acute lymphoblastic leukemia (ALL) remain substantially dismal. The aim of the present study was to evaluate the outcome in terms of survival in a cohort of adult patients with ALL who received allogeneic hematopoietic stem cell transplantation (alloSCT) between 2013 and 2023. Methods: This was a single-center observational retrospective study including all consecutive adult patients with ALL who received an alloSCT between April 2013 and April 2023 at the Stem Cell Transplant Center AOU Città della Salute e della Scienza of Torino. The primary endpoints were overall survival (OS), graft-versus-host disease (GVHD) Relapse-Free Survival (GRFS), Leukemia-Free Survival (LFS) and cumulative incidence (CI) of Non-Relapse Mortality (NRM). Results: The 4-year OS and LFS were 63.4% and 48.1%, respectively, and the 1-year GRFS was 42.9%. The 1-year CI of bloodstream infections (BSI), invasive fungal infections and NRM were 38%, 7% and 18.4%, respectively. Multivariate analysis showed that the use of total body irradiation (TBI), a time interval from diagnosis to alloSCT less than 7 months and female gender were factors significantly associated with better OS. Relapse of the underlying malignancy and BSI were the main causes of death. Conclusion: Our study suggests that alloSCT from a matched sibling donor (MSD) and alternative donors may be considered an effective tool for patients with ALL achieving a CR.