Frontiers in Oncology (Jun 2021)
New-Onset Severe Cytopenia After CAR-T Cell Therapy: Analysis of 76 Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia
- Linqin Wang,
- Linqin Wang,
- Linqin Wang,
- Linqin Wang,
- Ruimin Hong,
- Ruimin Hong,
- Ruimin Hong,
- Ruimin Hong,
- Linghui Zhou,
- Linghui Zhou,
- Linghui Zhou,
- Linghui Zhou,
- Fang Ni,
- Fang Ni,
- Fang Ni,
- Fang Ni,
- Mingming Zhang,
- Mingming Zhang,
- Mingming Zhang,
- Mingming Zhang,
- Houli Zhao,
- Houli Zhao,
- Houli Zhao,
- Houli Zhao,
- Wenjun Wu,
- Wenjun Wu,
- Wenjun Wu,
- Wenjun Wu,
- Yiyun Wang,
- Yiyun Wang,
- Yiyun Wang,
- Yiyun Wang,
- Shuyi Ding,
- Alex H. Chang,
- Yongxian Hu,
- Yongxian Hu,
- Yongxian Hu,
- Yongxian Hu,
- He Huang,
- He Huang,
- He Huang,
- He Huang
Affiliations
- Linqin Wang
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Linqin Wang
- Institute of Hematology, Zhejiang University, Hangzhou, China
- Linqin Wang
- Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
- Linqin Wang
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China
- Ruimin Hong
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Ruimin Hong
- Institute of Hematology, Zhejiang University, Hangzhou, China
- Ruimin Hong
- Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
- Ruimin Hong
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China
- Linghui Zhou
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Linghui Zhou
- Institute of Hematology, Zhejiang University, Hangzhou, China
- Linghui Zhou
- Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
- Linghui Zhou
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China
- Fang Ni
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Fang Ni
- Institute of Hematology, Zhejiang University, Hangzhou, China
- Fang Ni
- Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
- Fang Ni
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China
- Mingming Zhang
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Mingming Zhang
- Institute of Hematology, Zhejiang University, Hangzhou, China
- Mingming Zhang
- Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
- Mingming Zhang
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China
- Houli Zhao
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Houli Zhao
- Institute of Hematology, Zhejiang University, Hangzhou, China
- Houli Zhao
- Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
- Houli Zhao
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China
- Wenjun Wu
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Wenjun Wu
- Institute of Hematology, Zhejiang University, Hangzhou, China
- Wenjun Wu
- Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
- Wenjun Wu
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China
- Yiyun Wang
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Yiyun Wang
- Institute of Hematology, Zhejiang University, Hangzhou, China
- Yiyun Wang
- Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
- Yiyun Wang
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China
- Shuyi Ding
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Alex H. Chang
- Clinical Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
- Yongxian Hu
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Yongxian Hu
- Institute of Hematology, Zhejiang University, Hangzhou, China
- Yongxian Hu
- Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
- Yongxian Hu
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China
- He Huang
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- He Huang
- Institute of Hematology, Zhejiang University, Hangzhou, China
- He Huang
- Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
- He Huang
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China
- DOI
- https://doi.org/10.3389/fonc.2021.702644
- Journal volume & issue
-
Vol. 11
Abstract
Although chimeric antigen receptor T (CAR-T) cell therapy has proven to be effective in treating relapsed or refractory B-cell hematological malignancies, severe hematological toxicities remain an intractable issue. This retrospective study assessed the characteristics and risk factors of new-onset severe cytopenia following CAR-T cell infusion in 76 patients with r/r acute lymphoblastic leukemia. The rates of new-onset severe cytopenia were high, including severe neutropenia (SN) (39/56, 70%), severe anemia (SA) (35/66, 53%), and severe thrombocytopenia (ST) (31/64, 48%). Comparatively, cohorts with higher cytokine release syndrome (CRS) grades had higher incidence of severe cytopenia with prolonged duration. Multivariable analyses showed that elevated maximum (max) lg D-dimer and delayed peak time of CRS are independent risk factors for SN recovery; increased max lg IL-10 and delayed CRS recovery are risk factors for SA; high max lg ferritin is a risk factor for ST; and longer period to CRS onset or CRS recovery and higher grade of CRS are risk factors for prolonged hematological toxicities. These observations led to the conclusion that profiles of CRS, including its duration, severity and serum markers are correlated to the incidence and recovery of new-onset severe cytopenia, prompting clinical intervention for post-CAR-T severe cytopenia.
Keywords
- acute lymphoblastic leukemia
- chimeric antigen receptor
- cytokine release syndrome
- severe cytopenia
- hematopoietic recovery
- prolonged hematological toxicity
