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

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

doi:10.3389/fonc.2021.702644

Cited by 32 publications

(37 citation statements)

References 27 publications

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“…Correlation analysis showed that there was a certain correlation between the grade of CRS and the severity of cytopenia, which highlighted CRS as a common risk factor for early severe cytopenia. This conclusion is consistent with previously reported findings ( 13 , 14 ). In addition, in our study, inflammatory indicators such as CRP and ferritin were substantially related to early hepatotoxicity, and spikes in cytokines, especially IL-6, were also significantly associated with early severe trilineage cytopenia, the rates of which were significantly elevated in groups with severe CRS in previous reports ( 22 ).…”

Section: Discussionsupporting

confidence: 94%

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Cytopenia after chimeric antigen receptor T cell immunotherapy in relapsed or refractory lymphoma

et al. 2022

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BackgroundPatients with relapsed or refractory (R/R) lymphomas have benefited from chimeric antigen receptor (CAR)-T-cell therapy. However, this treatment is linked to a high frequency of adverse events (AEs), such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and hematologic toxicity. There has been increasing interest in hematological toxicity in recent years, as it can result in additional complications, such as infection or hemorrhage, which remain intractable.MethodsWe conducted a retrospective, single-institution study to evaluate the patterns and outcomes of cytopenia following CAR-T-cell infusion and potential associated factors.ResultsOverall, 133 patients with R/R lymphoma who received CAR-T-cell therapy from June, 2017 to April, 2022 were included in this analysis. Severe neutropenia, anemia and thrombocytopenia occurred frequently (71, 30 and 41%, respectively) after CAR-T-cell infusion. A total of 98% of severe neutropenia and all severe thrombocytopenia cases occurred in the early phase. Early severe cytopenia was associated with CRS incidence and severity, as well as peak inflammatory factor (IL-6, C-reactive protein (CRP), and ferritin) levels. In multivariate analysis, prior hematopoietic stem cell transplantation (HSCT), baseline hemoglobin (HB), and lymphodepleting chemotherapy were independent adverse factors associated with early severe cytopenia. In addition, 18% and 35% of patients had late neutrophil- and platelet (PLT)-related toxicity, respectively. In multivariate analysis, lower baseline PLT count was an independent factor associated with late thrombocytopenia. More severe cytopenia was associated with higher infection rates and poorer survival.ConclusionsThis research indicates that improved selection of patients and management of CRS may help to decrease the severity of cytopenias and associated AEs and improve survival following CAR-T-cell therapy.Clinical Trial Registrationhttps://www.clinicaltrials.gov/ct2/show/NCT03196830, identifier NCT03196830.

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Section: Discussionsupporting

confidence: 94%

“…Similarly, any-grade cytopenia occurred in 44% of patients in the JULIET study ( 11 ). Severe cytopenia may result in higher risks of infection ( 12 ) and hemorrhage, requiring more blood transfusion support ( 13 ). Transfusion-related responses, iron overload, and circulatory overload are relevant to continuous transfusion needs.…”

Section: Introductionmentioning

confidence: 99%

Cytopenia after chimeric antigen receptor T cell immunotherapy in relapsed or refractory lymphoma

et al. 2022

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“…Besides B cell and plasma cell depletion secondary to on-target off-tumor effects, cytopenia of other cell lineages is a well-documented CAR T-cell-related adverse event. Several studies have demonstrated high incidence of cytopenia after CAR T-cells [14,42,47,[59][60][61][62]. The mechanism of cytopenia is multifactorial and not yet well understood [63,64].…”

Section: Hematologic and Immune Recovery After Car T-cell Therapymentioning

confidence: 99%

Infectious complications, immune reconstitution, and infection prophylaxis after CD19 chimeric antigen receptor T-cell therapy

Wudhikarn

Perales

2022

Bone Marrow Transplant

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CD19-targeted chimeric antigen receptor (CAR) T-cell becomes a breakthrough therapy providing excellent remission rates and durable disease control for patients with relapsed/refractory (R/R) hematologic malignancies. However, CAR T-cells have several potential side effects including cytokine release syndrome, neurotoxicities, cytopenia, and hypogammaglobulinemia. Infection has been increasingly recognized as a complication of CAR T-cell therapy. Several factors predispose CAR T-cell recipients to infection. Fortunately, although studies show a high incidence of infection post-CAR T-cells, most infections are manageable. In contrast to patients who undergo hematopoietic stem cell transplant, less is known about post-CAR T-cell immune reconstitution. Therefore, evidence regarding antimicrobial prophylaxis and vaccination strategies in these patients is more limited. As CAR T-cell therapy becomes the standard treatment for R/R B lymphoid malignancies, we should expect a larger impact of infections in these patients and the need for increased clinical attention. Studies exploring infection and immune reconstitution after CAR T-cell therapy are clinically relevant and will provide us with a better understanding of the dynamics of immune function after CAR T-cell therapy including insights into appropriate strategies for prophylaxis and treatment of infections in these patients. In this review, we describe infections in recipients of CAR T-cells, and discuss risk factors and potential mitigation strategies.

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“…Hematological toxicity (HT) is another common AE with an incidence of higher than 90% and is associated with dismal outcomes (14-16). For instance, Sarah and Wang et al reported that prolonged HT (PHT) is associated with a shorter 1-year OS in patients with R/R diffuse large B-cell lymphoma and acute lymphoblastic leukemia (17,18). However, there are relatively few large-sample studies on post-CAR-T-cell therapy PHT among patients with R/R MM, and studies on the correlation between PHT and prognosis are lacking.…”

Section: Introductionmentioning

confidence: 99%

Prolonged hematological toxicity in patients receiving BCMA/CD19 CAR-T-cell therapy for relapsed or refractory multiple myeloma

Zhao

Sun

et al. 2022

Front. Immunol.

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Although chimeric antigen receptor T (CAR-T) cell therapy has been indicated to be effective in treating relapsed or refractory multiple myeloma (R/R MM), severe hematological toxicity (HT) remains an intractable issue. This study enrolled 54 patients with R/R MM following combined infusion of anti-CD19 and anti-BCMA CAR-T cells. The results showed that the rates of severe cytopenia were high, including severe neutropenia (28/54, 52%), severe anemia (15/54, 28%), and severe thrombocytopenia (18/54, 33%). Moreover, the incidence of prolonged HT (PHT) on Day 28 post-infusion was 52% (28/54), including 46% for severe neutropenia, 30% for severe anemia, and 31% for severe thrombocytopenia. Patients with PHT had a poorer median progression-free survival (PFS) and overall survival (OS) than patients without PHT (P=0.011; P=0.007). Furthermore, Cox regression analyses showed that PHT was an independent risk factor for PFS and OS. Univariate analyses showed that IFNγ (OR: 1.046; 95% CI: 1.002-1.093, P=0.042) and severe HT after lymphodepletion chemotherapy (OR: 0.082; 95% CI: 0.017-0.404; P=0.002) were independent risk factors for PHT. In conclusion, these results indicated that PHT was associated with poor outcomes following CAR-T-cell therapy in MM patients. Early detection and management of PHT would be beneficial for the prevention of life-threatening complications and improvement in the survival of patients after CAR-T-cell therapy.Clinical trial registrationThis trial was registered on 1 May 2017 at http://www.chictr.org.cn as ChiCTR-OIC-17011272.

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

Cited by 32 publications

References 27 publications

Cytopenia after chimeric antigen receptor T cell immunotherapy in relapsed or refractory lymphoma

Cytopenia after chimeric antigen receptor T cell immunotherapy in relapsed or refractory lymphoma

Infectious complications, immune reconstitution, and infection prophylaxis after CD19 chimeric antigen receptor T-cell therapy

Prolonged hematological toxicity in patients receiving BCMA/CD19 CAR-T-cell therapy for relapsed or refractory multiple myeloma

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