Assessment and predictive ability of the absolute neutrophil count in peripheral blood for in vivo CAR T cells expansion and CRS.

BACKGROUND: Chimeric antigen receptor (CAR) T cell therapy is an advanced and effective immunotherapy for relapsed or refractory B-cell malignancies. High expansion of CAR T cells in vivo and durable antitumor activity indicate a persistent therapeutic response. However, this treatment is linked to a high frequency of adverse events, such as cytokine release syndrome (CRS), which affects its efficacy and can even be life-threatening. At present, a variety of markers associated with clinical response and treatment toxicity after CAR T cells infusion have been reported. Although these biomarkers can act as effective indicators reflecting CAR T cells expansion as well as CRS, they fail to predict the expansion rate of CAR T cells. Hence, further investigation is urgent to find a new biomarker to fill this void. METHODS: We analyzed the association between the absolute neutrophil count (ANC) and CAR expansion and CRS in 45 patients with B-cell malignancies from two clinical trials. We proposed that ANC could be a practical biomarker for CAR T cells expansion and CRS, and conducted a feasibility analysis on its predictive ability. RESULTS: In this study, 17 B-cell hematological malignancy patients with anti-B-cell maturation antigen CAR-treated and 28 with CAR19/22 T-cell-treated were enrolled and divided into an ANC-absence group and an ANC-presence group. The results showed that ANC absence correlated positively with CAR expansion and the expansion rate. The ANC can be used as a predictive marker for CAR T cells expansion. Moreover, the patients with ANC absence experienced a more severe CRS, and ANC performed a predictive ability for CRS. In addition, the peak serum concentration of several cytokines involved in CRS was higher in patients with ANC absence. CONCLUSION: Thus, we suggest ANC as an evaluative and predictive biomarker for CAR expansion and CRS during CAR T cell therapy, which can help to maximize clinical efficacy, reduce treatment-related toxicity and prolong survival.

Effectiveness of comprehensive geriatric assessment intervention on quality of life, caregiver burden and length of hospital stay: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Comprehensive geriatric assessment (CGA) interventions can improve functional ability and reduce mortality in older adults, but the effectiveness of CGA intervention on the quality of life, caregiver burden, and length of hospital stay remains unclear. The study aimed to determine the effectiveness of CGA intervention on the quality of life, length of hospital stay, and caregiver burden in older adults by conducting meta-analyses of randomised controlled trials (RCTs). METHODS: A literature search in PubMed, Embase, and Cochrane Library was conducted for papers published before February 29, 2020, based on inclusion criteria. Standardised mean difference (SMD) or mean difference (MD) with 95% confidence intervals (CIs) was calculated using the random-effects model. Subgroup analyses, sensitivity analyses, and publication bias analyses were also conducted. RESULTS: A total of 28 RCTs were included. Overall, the intervention components common in different CGA intervention models were interdisciplinary assessments and team meetings. Meta-analyses showed that CGA interventions improved the quality of life of older people (SMD = 0.12; 95% CI = 0.03 to 0.21; P = 0.009) compared to usual care, and subgroup analyses showed that CGA interventions improved the quality of life only in participants' age > 80 years and at follow-up ≤3 months. The change value of quality of life in the CGA intervention group was better than that in the usual care group on six dimensions of the 36-Item Short-Form Health Survey questionnaire (SF-36). Also, compared to usual care, the CGA intervention reduced the caregiver burden (SMD = - 0.56; 95% CI = - 0.97 to - 0.15, P = 0.007), but had no significant effect on the length of hospital stay. CONCLUSIONS: CGA intervention was effective in improving the quality of life and reducing caregiver burden, but did not affect the length of hospital stay. It is recommended that future studies apply the SF-36 to evaluate the impact of CGA interventions on the quality of life and provide supportive strategies for caregivers as an essential part of the CGA intervention, to find additional benefits of CGA interventions.