Characterization of HLH-like manifestations as a CRS variant in patients receiving CD22 CAR T cells.

Autor:	Lichtenstein DA; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD., Schischlik F; Cancer Data Science Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, MD., Shao L; Center for Cellular Engineering, Department of Transfusion Medicine, NIH Clinical Center, Bethesda, MD., Steinberg SM; Biostatistics and Data Management Section, Center for Cancer Research, Bethesda, MD., Yates B; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD., Wang HW; Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD., Wang Y; Applied Developmental Research Directorate, Leidos Biomedical Research, Inc, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD., Inglefield J; Applied Developmental Research Directorate, Leidos Biomedical Research, Inc, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD., Dulau-Florea A; Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD., Ceppi F; Department of Pediatrics, Seattle Children's Hospital, Seattle, WA.; Paediatric Haematology-Oncology Unit, Division of Paediatrics, Department Woman-Mother-Child, University Hospital of Lausanne, Lausanne, Switzerland., Hermida LC; Cancer Data Science Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, MD.; Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD., Stringaris K; Transplantation Immunology, National Heart, Lung and Blood Institute, Bethesda, MD., Dunham K; Applied Developmental Research Directorate, Leidos Biomedical Research, Inc, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD., Homan P; Center for Cancer Research Collaborative Bioinformatics Resource, National Cancer Institute, National Institutes of Health, Bethesda, MD.; Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Fredrick, MD., Jailwala P; Center for Cancer Research Collaborative Bioinformatics Resource, National Cancer Institute, National Institutes of Health, Bethesda, MD.; Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Fredrick, MD., Mirazee J; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD., Robinson W; Cancer Data Science Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, MD.; Paediatric Haematology-Oncology Unit, Division of Paediatrics, Department Woman-Mother-Child, University Hospital of Lausanne, Lausanne, Switzerland., Chisholm KM; Department of Laboratories, Seattle Children's Hospital, Seattle, WA., Yuan C; Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD., Stetler-Stevenson M; Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD., Ombrello AK; Inflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD; and., Jin J; Center for Cellular Engineering, Department of Transfusion Medicine, NIH Clinical Center, Bethesda, MD., Fry TJ; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.; University of Colorado Anschutz Medical Campus and Center for Cancer and Blood Disorders, Children's Hospital of Colorado, Aurora, CO., Taylor N; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD., Highfill SL; Center for Cellular Engineering, Department of Transfusion Medicine, NIH Clinical Center, Bethesda, MD., Jin P; Center for Cellular Engineering, Department of Transfusion Medicine, NIH Clinical Center, Bethesda, MD., Gardner RA; Applied Developmental Research Directorate, Leidos Biomedical Research, Inc, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD., Shalabi H; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD., Ruppin E; Cancer Data Science Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, MD., Stroncek DF; Center for Cellular Engineering, Department of Transfusion Medicine, NIH Clinical Center, Bethesda, MD., Shah NN; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2021 Dec 16; Vol. 138 (24), pp. 2469-2484.
DOI:	10.1182/blood.2021011898
Abstrakt:	Chimeric antigen receptor (CAR) T-cell toxicities resembling hemophagocytic lymphohistiocytosis (HLH) occur in a subset of patients with cytokine release syndrome (CRS). As a variant of conventional CRS, a comprehensive characterization of CAR T-cell-associated HLH (carHLH) and investigations into associated risk factors are lacking. In the context of 59 patients infused with CD22 CAR T cells where a substantial proportion developed carHLH, we comprehensively describe the manifestations and timing of carHLH as a CRS variant and explore factors associated with this clinical profile. Among 52 subjects with CRS, 21 (40.4%) developed carHLH. Clinical features of carHLH included hyperferritinemia, hypertriglyceridemia, hypofibrinogenemia, coagulopathy, hepatic transaminitis, hyperbilirubinemia, severe neutropenia, elevated lactate dehydrogenase, and occasionally hemophagocytosis. Development of carHLH was associated with preinfusion natural killer(NK) cell lymphopenia and higher bone marrow T-cell:NK cell ratio, which was further amplified with CAR T-cell expansion. Following CRS, more robust CAR T-cell and CD8 T-cell expansion in concert with pronounced NK cell lymphopenia amplified preinfusion differences in those with carHLH without evidence for defects in NK cell mediated cytotoxicity. CarHLH was further characterized by persistent elevation of HLH-associated inflammatory cytokines, which contrasted with declining levels in those without carHLH. In the setting of CAR T-cell mediated expansion, clinical manifestations and immunophenotypic profiling in those with carHLH overlap with features of secondary HLH, prompting consideration of an alternative framework for identification and management of this toxicity profile to optimize outcomes following CAR T-cell infusion. (© 2021 by The American Society of Hematology.)
Databáze:	MEDLINE
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