New-Onset Severe Cytopenia After CAR-T Cell Therapy: Analysis of 76 Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia

Linqin Wang; Ruimin Hong; Linghui Zhou; Fang Ni; Mingming Zhang; Houli Zhao; Wenjun Wu; Yiyun Wang; Shuyi Ding; Alex H Chang; Yongxian Hu; He Huang

doi:10.3389/fonc.2021.702644

New-Onset Severe Cytopenia After CAR-T Cell Therapy: Analysis of 76 Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia

Front Oncol. 2021 Jun 30:11:702644. doi: 10.3389/fonc.2021.702644. eCollection 2021.

Authors

Linqin Wang^{1

2

3

4}, Ruimin Hong^{1

2

3

4}, Linghui Zhou^{1

2

3

4}, Fang Ni^{1

2

3

4}, Mingming Zhang^{1

2

3

4}, Houli Zhao^{1

2

3

4}, Wenjun Wu^{1

2

3

4}, Yiyun Wang^{1

2

3

4}, Shuyi Ding¹, Alex H Chang⁵, Yongxian Hu^{1

2

3

4}, He Huang^{1

2

3

4}

Affiliations

¹ Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
² Institute of Hematology, Zhejiang University, Hangzhou, China.
³ Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China.
⁴ Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China.
⁵ Clinical Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

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; hematopoietic recovery; prolonged hematological toxicity; severe cytopenia.