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The adaptive T cell immune response requires cellular plasticity to generate distinct subsets with diverse functional and migratory capacities. Studies of CAR T cells have primarily focused on a limited number of phenotypic markers in blood, representing an incomplete view of CAR T cell complexity. Here, we adapted mass cytometry to simultaneously analyze trafficking and functional proteins expression in CD19 CAR T cells across patients' tissues, including leukapheresis T cells, CAR product, CAR T cells in peripheral blood, bone marrow, and cerebrospinal fluid post infusion and correlate them with phenotypes. This approach revealed spatiotemporal plasticity of CAR T cells. Patients' CAR product revealed upregulation in many trafficking and activation molecules compared to leukapheresis T cells as baseline. Including statistically significant upregulation in CD4 and CD8 integrin-β7, CD4 granzyme B, and CD11a as well as CD8 CD25 and CD95. Moreover, patients' tissues showed spatiotemporal alteration in trafficking, activation, maturation, and exhaustion features, with a distinct signature in the central nervous system niche. Compared to peripheral blood samples, cerebrospinal fluid samples were statistically significant enriched in CD4 and CD8 trafficking and memory phenotype proteins integrin β7, CCR7, CXCR4, and CD8 CD69. Our data provide a potential framework to remodel CAR T cells and enhance immunotherapy efficacy. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic cell transplantation (alloHCT) is a curative option for the treatment of eligible patients with hematological malignancies. This modality confers a risk for life-threatening complications, including the rare and underdiagnosed complication of donor-derived leukemia (DDL). DDL differs from relapse of the original malignancy in that DDL originates from the donor stem cells and is unrelated to the original diagnosis. Because DDL may be the same lineage as the original diagnosis, it is difficult to identify these cases and many remain unrecognized. There is no consensus of how to approach the treatment of patients with DDL, and their prognosis is poor considering that patients with DDL have already been treated for their original leukemia and have undergone alloHCT. DDL occurs following transplants using any donor stem cell source (bone marrow, peripheral blood and cord blood) and any donor type (matched/unmatched, related/unrelated and haploidentical). Both donor and recipient factors contribute to the development of DDL, and a better understanding of these factors is crucial to reduce the risk for the development of DDL. In this review, we provide an overview of DDL, including the incidence, diagnosis, etiology, prognosis, and treatment. [ABSTRACT FROM AUTHOR]

AbstractReactive pleocytosis in the CSF has been observed with blinatumomab but has not been well-described. We performed a retrospective study of 88 patients who received intrathecal chemotherapy (IT) while on blinatumomab with CSF analyzed to determine if pleocytosis had an impact efficacy and safety. Blinatumomab was used for relapsed/refractory 62.5%, MRD-positive 31.8%, and consolidation in MRD-negative 5.7%. The incidence of pleocytosis in CSF was 51% and was more frequent after day 15 (55.8% vs. 18.2%, p = 0.025). Pleocytosis did not impact CR, clearance of MRD positivity, PFS and OS rates. Lower incidence of non-CNS extramedullary relapse was seen (3.7% vs. 30.8%, p = 0.011) with pleocytosis in CSF. Analysis of CSF by flow cytometry showed median CD4:CD8 ratio of 1.34. In conclusion, CSF pleocytosis is prevalent with blinatumomab but only demonstrated lower rates of non-CNS extramedullary relapse but no impact on CNS relapse or neurotoxicity. [ABSTRACT FROM AUTHOR]