دورية أكاديمية
Prolonged cytopenias after immune effector cell therapy and lymphodepletion in patients with leukemia, lymphoma and solid tumors.
| العنوان: | Prolonged cytopenias after immune effector cell therapy and lymphodepletion in patients with leukemia, lymphoma and solid tumors. |
|---|---|
| المؤلفون: | Miller A; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX, USA., Daum R; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX, USA; Dell Medical School, University of Texas at Austin, Austin, TX, USA., Wang T; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX, USA; Dan L Duncan Comprehensive Cancer Center, Houston, TX, USA., Wu M; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX, USA; Dan L Duncan Comprehensive Cancer Center, Houston, TX, USA., Tat C; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX, USA; Department of Pediatrics, Texas Children's Hospital, Houston, TX, USA., Pfeiffer T; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX, USA; Department of Pediatrics, Texas Children's Hospital, Houston, TX, USA; Department of Pediatrics, Division of Hematology/Oncology, Washington University School of Medicine, St. Louis, MO, USA., Navai S; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX, USA; Department of Pediatrics, Texas Children's Hospital, Houston, TX, USA., Heczey A; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX, USA; Dan L Duncan Comprehensive Cancer Center, Houston, TX, USA; Department of Pediatrics, Texas Children's Hospital, Houston, TX, USA., Hegde M; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX, USA; Dan L Duncan Comprehensive Cancer Center, Houston, TX, USA; Department of Pediatrics, Texas Children's Hospital, Houston, TX, USA., Ahmed N; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX, USA; Dan L Duncan Comprehensive Cancer Center, Houston, TX, USA; Department of Pediatrics, Texas Children's Hospital, Houston, TX, USA; Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA., Whittle SB; Dan L Duncan Comprehensive Cancer Center, Houston, TX, USA; Department of Pediatrics, Texas Children's Hospital, Houston, TX, USA., Hill L; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX, USA; Dan L Duncan Comprehensive Cancer Center, Houston, TX, USA., Martinez C; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX, USA; Dan L Duncan Comprehensive Cancer Center, Houston, TX, USA; Department of Pediatrics, Texas Children's Hospital, Houston, TX, USA., Krance R; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX, USA; Dan L Duncan Comprehensive Cancer Center, Houston, TX, USA; Department of Pediatrics, Texas Children's Hospital, Houston, TX, USA., Ramos CA; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX, USA; Dan L Duncan Comprehensive Cancer Center, Houston, TX, USA; Department of Pediatrics, Texas Children's Hospital, Houston, TX, USA., Rouce RH; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX, USA; Dan L Duncan Comprehensive Cancer Center, Houston, TX, USA; Department of Pediatrics, Texas Children's Hospital, Houston, TX, USA., Lulla P; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX, USA; Dan L Duncan Comprehensive Cancer Center, Houston, TX, USA., Heslop HE; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX, USA; Dan L Duncan Comprehensive Cancer Center, Houston, TX, USA., Omer B; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX, USA; Dan L Duncan Comprehensive Cancer Center, Houston, TX, USA; Department of Pediatrics, Texas Children's Hospital, Houston, TX, USA., Shekar M; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX, USA; Department of Pediatrics, Texas Children's Hospital, Houston, TX, USA. Electronic address: Meghan.shekar@bcm.edu. |
| المصدر: | Cytotherapy [Cytotherapy] 2024 May 08. Date of Electronic Publication: 2024 May 08. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: England NLM ID: 100895309 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1477-2566 (Electronic) Linking ISSN: 14653249 NLM ISO Abbreviation: Cytotherapy Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2013- : London : Elsevier Original Publication: Oxford, England : ISIS Medical Media, c1999- |
| مستخلص: | Background Aims: The success of chimeric antigen receptor (CAR) T-cell therapy in treating B-cell malignancies has led to the evaluation of CAR T-cells targeting a variety of other malignancies. Although the efficacy of CAR T-cells is enhanced when administered post-lymphodepleting chemotherapy, this can trigger bone marrow suppression and sustained cytopenia after CD19.CAR T-cell therapy. Additionally, systemic inflammation associated with CAR T-cell activity may contribute to myelosuppression. Cytopenias, such as neutropenia and thrombocytopenia, elevate the risk of severe infections and bleeding, respectively. However, data on the incidence of prolonged cytopenias after immune effector therapy in the solid tumor context remain limited. Objective: We compared the incidence of prolonged cytopenias after immune effector therapy including genetically modified T-cells, virus-specific T-cells (VSTs) and NKT-cells, as well non-gene-modified VSTs for leukemia, lymphoma, and solid tumors (ST) to identify associated risk factors. Methods: A retrospective analysis was conducted of 112 pediatric and adult patients with relapsed and/or refractory cancers who received lymphodepleting chemotherapy followed by immune effector therapy. Patients treated with 13 distinct immune effector cell therapies through 11 single-center clinical trials and 2 commercial products over a 6-year period were categorized into 3 types of malignancies: leukemia, lymphoma and ST. We obtained baseline patient characteristics and adverse events data for each participant, and tracked neutrophil and platelet counts following lymphodepletion. Results: Of 112 patients, 104 (92.9%) experienced cytopenias and 88 (79%) experienced severe cytopenias. Patients with leukemia experienced significantly longer durations of severe neutropenia (median duration of 14 days) compared with patients with lymphoma (7 days) or ST (11 days) (P = 0.002). Patients with leukemia also had a higher incidence of severe thrombocytopenia (74.1%), compared with lymphoma (46%, P = 0.03) and ST (14.3%, P < 0.0001). Prolonged cytopenias were significantly associated with disease type (63% of patients with leukemia, 44% of patients with lymphoma, and 22.9% of patients with ST, P = 0.006), prior hematopoietic stem cell transplant (HSCT) (66.7% with prior HSCT versus 38.3% without prior HSCT, P = 0.039), and development of immune effector cell-associated neurotoxicity syndrome (ICANS) (75% with ICANS versus 38% without ICANS, P = 0.027). There was no significant association between prolonged cytopenias and cytokine release syndrome. Conclusions: Immune effector recipients often experience significant cytopenias due to marrow suppression following lymphodepletion regardless of disease, but prolonged severe cytopenias are significantly less common after treatment of patients with lymphoma and solid tumors. (Published by Elsevier Inc.) |
| فهرسة مساهمة: | Keywords: CAR T cells; cytopenia; hematologic toxicity; immune effector cells |
| تواريخ الأحداث: | Date Created: 20240531 Latest Revision: 20240531 |
| رمز التحديث: | 20240531 |
| DOI: | 10.1016/j.jcyt.2024.04.075 |
| PMID: | 38819365 |
| قاعدة البيانات: | MEDLINE |
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