The Clinical Frailty Scale can indicate prognosis and care requirements on discharge in oncology and haemato-oncology inpatients: A cohort study.

OBJECTIVES: Routinely used performance status scales, assessing patients' suitability for cancer treatment, have limited ability to account for multimorbidity, frailty and cognition. The Clinical Frailty Scale (CFS) is a suggested alternative, but research detailing its use in oncology is limited. This study aims to evaluate if CFS is associated with prognosis and care needs on discharge in oncology inpatients. METHODS: We evaluated a large, single-centre cohort study in this research. CFS was recorded for adult inpatients at a Regional Cancer Centre. The associations between CFS, age, tumour type, discharge destination and care requirements and survival were evaluated. RESULTS AND CONCLUSIONS: A total of 676 patients were included in the study. Levels of frailty were high (Median CFS 6, 81.8% scored ≥5) and CFS correlated with performance status (R = 0.13: P = 0.047). Patients who were frail (CFS ≥ 5) were less likely to be discharged home (62.9%) compared with those who were not classed as frail (86.1%) (OR 3.6 [95%CI 2.1 to 6.3]: P < 0.001). Higher CFS was significantly associated with poorer prognosis in all ages. Solid organ malignancy (hazard ratio [HR] 2.60 [95%CI 2.05-3.32]) and CFS (HR 1.43 [95%CI 1.29-1.59]; P < 0.001) were independently associated with poorer survival. This study demonstrated that CFS may help predict prognosis in adult oncology inpatients of any age. This may aid informed shared decision-making in this setting. Future work should establish if routine CFS measurement can aid the appropriate prescription of systemic therapy and enable early conversations about discharge planning.

Donor monocyte-derived macrophages promote human acute graft-versus-host disease.

Myelopoiesis is invariably present and contributes to pathology in animal models of graft-versus-host disease (GVHD). In humans, a rich inflammatory infiltrate bearing macrophage markers has also been described in histological studies. In order to determine the origin, functional properties, and role in pathogenesis of these cells, we isolated single-cell suspensions from acute cutaneous GVHD and subjected them to genotype, transcriptome, and in vitro functional analysis. A donor-derived population of CD11c+CD14+ cells was the dominant population of all leukocytes in GVHD. Surface phenotype and NanoString gene expression profiling indicated the closest steady-state counterpart of these cells to be monocyte-derived macrophages. In GVHD, however, there was upregulation of monocyte antigens SIRPα and S100A8/9 transcripts associated with leukocyte trafficking, pattern recognition, antigen presentation, and costimulation. Isolated GVHD macrophages stimulated greater proliferation and activation of allogeneic T cells and secreted higher levels of inflammatory cytokines than their steady-state counterparts. In HLA-matched mixed leukocyte reactions, we also observed differentiation of activated macrophages with a similar phenotype. These exhibited cytopathicity to a keratinocyte cell line and mediated pathological damage to skin explants independently of T cells. Together, these results define the origin, functional properties, and potential pathogenic roles of human GVHD macrophages.