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Introduction: Chimeric antigen receptor T (CAR-T) cell therapy, emerging as an efficient treatment option for patients with secondary central nervous system (CNS) lymphoma, is frequently complicated with immune effector cell-associated neurotoxicity syndrome (ICANS). Case Presentation: We report a case of a 64-year-old woman with transformed follicular lymphoma, developing high-grade ICANS with eosinophilic pleocytosis following third-line therapy with CAR-T cells (tisagenlecleucel). During bridging therapy, she declined neurologically and was diagnosed with secondary CNS lymphoma. She received methotrexate-cytarabine-thiotepa-rituximab regimen with clinical and radiological improvement. Post-CAR-T cell infusion she developed cytokine release syndrome grade II and ICANS grade III. Given the lack of response to steroids, anakinra was initiated with complete ICANS resolution. Cerebrospinal fluid (CSF) analysis, performed only on day +10 due to thrombocytopenia, revealed eosinophils, while infections were excluded. Conclusion: This report emphasizes the importance of CSF analysis in individuals with CAR-T-related neurotoxicity for elucidating the role of specific immune cells in such complications. [ABSTRACT FROM AUTHOR]

Background: Chronic lymphocytic leukemia (CLL) is a heterogeneous B-cell malignancy, affecting mainly older adults. Despite the recent introduction of multiple targeted agents, CLL remains an incurable disease. Cellular therapy is a promptly evolving area that has developed over the last decades from such standard of care as hematopoietic cell transplantation (HCT) to the novel treatment modalities employing genetically engineered immune cells. Summary: Tailoring the proper treatment for each patient is warranted and should take into account the disease biology, patient characteristics, and the available treatment modalities. Nowadays, the most broadly applied cellular therapies for CLL management are HCT and chimeric antigen receptor-T (CAR-T) cells. However, CAR-T cell therapy is currently not yet approved in CLL, and the appropriate sequencing for the administration of these agents remains to be clarified. Key Messages: The current review will discuss various available cellular treatment options, their advances and limitations, as well as the optimal timing for the employment of such therapies in CLL patients. [ABSTRACT FROM AUTHOR]

Objectives: Midostaurin, a multikinase and FLT3 inhibitor, is the first non‐chemotherapy agent approved and widely adopted for the treatment of FLT3‐ITD acute myeloid leukemia (AML). Yet, its role in improving survival of patients referred to allogeneic stem cell transplantation (allo‐SCT) in first complete remission (CR1) needs to be defined. Methods: This multicenter study retrospectively evaluated the outcome of 119 FLT3‐ITD AML patients [59 (49.6%) males and 60 females] intensively treated between 2015 and 2019 at five Israeli centers. In our cohort, allo‐SCT in CR1 was widely implemented (47%) and patient stratification was based on the current allelic ratio (AR) cutoff of 0.5. Results: Ninety‐eight patients (82.3%) achieved CR1/CR with incomplete count recovery (CRi). Death during induction was reported in 7 (5.9%) patients. In multivariate analysis, midostaurin use and allo‐SCT in CR1 were the most significant factors affecting overall survival (OS). Midostaurin incorporation in chemotherapy regimens significantly improved CR + CRi rates (P =.002), reduced relapse rates (P =.02), and was remarkably advantageous for high‐AR patients (2‐year OS 82%). In low‐AR patients, the midostaurin effect was much less prominent. Conclusions: Our results demonstrate benefits of midostaurin incorporation in intensive chemotherapy regimens, particularly for high‐AR AML patients to whom it should be offered along with allo‐SCT in CR1. [ABSTRACT FROM AUTHOR]

Introduction: Systemic sclerosis is a complex disease that affects various target organs, making it difficult to assess response and determine remission or relapse. A baseline Neutrophil-to-Lymphocyte Ratio (NLR) >2.95 is associated with severe progressive skin and lung disease and decreased 5-year survival in systemic sclerosis (SSc). However, it is unknown whether NLR changes in response to treatment., Objective: To retrospectively evaluate NLR changes as a biomarker for treatment response in SSc., Methods: Progressive diffuse SSc patients who were treated with autologous hematopoietic stem cell transplantation (AHSCT group), with combination therapy of rituximab and mycophenolate mofetil (combination group) or CAR-T cell therapy (CAR-T group) were recruited, along with healthy controls (HC group). NLR, modified Rodnan Skin Score (mRSS) and forced vital capacity (FVC)% predicted were repeatedly assessed over 2 years., Results: Fifteen patients were recruited in the AHSCT group, 15 in the combination group, and six patients in the CAR-T group. Baseline mean NLR was high (>2.95) in AHSCT, combination groups, and CAR-T compared with HC. All treatment arms showed a statistically significant decrease in mRSS values and an increase in FVC% at each time point up to 12 months. In a linear mixed model, NLR significantly decreased up to 24 months only in the AHSCT group. NLR correlated with mRSS and FVC exclusively in the AHSCT group. NLR increased above 3 in two patients who experienced a relapse after AHSCT., Conclusion: NLR is a simple biomarker that correlated with outcome measures in SSc following AHSCT, but not with conventional therapy or CAR-T therapy. It is suggested that a decrease in NLR following AHSCT may indicate remission, whereas an increase may be associated with exacerbation. Further research is needed to validate these novel findings., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Using immunotherapy to fight cancer, and specifically, the use of engineered T-cells expressing a chimeric receptor against an antigen found on malignant cells (chimeric antigen receptor, CAR-T cells) constitutes a significant breakthrough in the treatment of the disease. In recent years, several CAR-T therapies have been approved in Europe and the USA, and some are already approved and funded through the national health basket in Israel, for the indications of diffuse large B-cell lymphoma, mantle cell lymphoma and B-cell acute lymphoblastic leukemia, after the failure of at least two lines of treatment. The treatment with CAR-T cells achieves prolonged remissions and even long-term cure of patients who had a very poor prognosis. However, the treatment involves significant side effects, and requires specific expertise in the management of patients both during the period of preparation for cell transplantation, and following the treatment. During the immediate post-infusion period, the most common adverse reactions are cytokine release syndrome (CRS) which stems from the activation of the immune system, and neurological toxicity that can accompany CRS. These effects require close monitoring, grading their severity, and providing anti-cytokine therapy or steroid therapy until control of symptoms is achieved. Later effects can be persistent cytopenias, immune over-activation, and prolonged immune deficiency. Treatments for additional indications and new CAR-T constructs are being developed and will allow more effective and safer treatment. This article summarizes the principles for CAR-T administration that, as currently provided in Israel, include the short- and long-term follow-up of the patients.

Outcomes of allogeneic hematopoietic stem cell transplantation (allo- HSCT) have improved in the recent decade; however, infections and graft-versus-host disease remain two leading complications significantly contributing to early transplant-related mortality. In past years, the human intestinal microbial composition (microbiota) has been found to be associated with various disease states, including cancer, response to cancer immunotherapy and to modulate the gut innate and adaptive immune response. In the setting of allo-HSCT, the intestinal microbiota diversity and composition appear to have an impact on infection risk, mortality and overall survival. Microbial metabolites have been shown to contribute to the health and integrity of intestinal epithelial cells during inflammation, thus mitigating graft-versus-host disease in animal models. While the cause-andeffect relationship between the intestinal microbiota and transplant-associated complications has not yet been fully elucidated, the above findings have already resulted in the implementation of various interventions aiming to restore the intestinal microbiota diversity and composition. Among others, these interventions include the administration of fecal microbiota transplantation. The present review, based on published data, is intended to define the role of the latter approach in the setting of allo-HSCT.