The Simplified Comorbidity Index: a new tool for prediction of nonrelapse mortality in allo-HCT.
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ABSTRACT:
SUBMITTER: Shouval R
PROVIDER: S-EPMC8905694 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Allogeneic antibodies against minor histocompatibility antigens encoded on the Y chromosome (HY-Abs) develop after hematopoietic cell transplant (HCT) of male recipients with female donors (F→M). However, the temporal association between HY-Ab development and chronic graft-versus-host disease (cGVHD) has yet to be elucidated. We studied 136 adult F→M HCT patients, with plasma prospectively collected through 3 years posttransplant, and measured immunoglobulin G against 6 H-Y antigens. Multiple HY-Abs were frequently detected beginning at 3 months posttransplant: 78 (57%) of F→M patients were seropositive for at least 1 of the 6 HY-Abs, and 3-month seropositivity for each HY-Ab was associated with a persistent seropositive response throughout the posttransplant follow-up period (P < .001 in each). There were no associations between pretransplant features and 3-month overall HY-Ab development. Detection of multiple HY-Abs at 3 months (represented by HY score) was significantly associated with an increased risk of cGVHD (P < .0001) and nonrelapse mortality (P < .01). Compared to clinical factors alone, the addition of HY score to clinical factors improved the predictive potential of cGVHD (P < .01). Monitoring HY-Ab development thus stratifies cGVHD risk in F→M HCT patients and may support preemptive prophylaxis therapy for cGVHD beginning at 3 months posttransplant.
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Project description:Allogeneic hematopoietic cell transplantation (HCT) can cure many nonmalignant conditions, but concern for morbidity and mortality remains. To help physicians estimate patient-specific transplant mortality risk, the HCT comorbidity index (HCT-CI) is used. However, pediatric physicians use the HCT-CI less frequently than adult counterparts. We used the Center for International Blood and Marrow Transplant Research database to expand the HCT-CI comorbidity definitions to be more inclusive of children and adolescent and young adult (AYA) patients, adding history of mechanical ventilation, history of invasive fungal infection, assessment of chronic kidney disease (CKD) by estimated glomerular filtration rate, expanding the definition of obesity, and adding an underweight category. A total of 2815 children and AYAs (<40 years old) who received first allogeneic HCT for nonmalignant diseases from 2008 to 2017 were included to create an expanded youth nonmalignant HCT-CI (expanded ynHCT-CI) and a simplified non-malignant (simplified ynHCT-CI) HCT-CI. The expanded comorbidities occurred frequently-history of mechanical ventilation (9.6%), history of invasive fungal infection (5.9%), mild CKD (12.2%), moderate/severe CKD (2.1%), obesity (10.9%), and underweight (14.5%). Thirty-nine percent of patients had an increase in their comorbidity score using the expanded ynHCT-CI, leading to a redistribution of scores: ynHCT-CI score 0 (35%), 1-2 (36.4%), and ≥3 (28.6%). Patients with an increase in their comorbidity score had an increased hazard of mortality compared to those whose score remained the same (hazard ratio = 1.41; 95% confidence interval, 1.01-1.98). Modifications to the HCT-CI can benefit children and AYA patients with nonmalignant diseases, creating a risk assessment tool that is clinically relevant and better captures comorbidity in this younger population.
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Project description:Respiratory viral infections are frequent in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT) and can potentially progress to lower respiratory tract infection (LRTI). The intestinal microbiota contributes to resistance against viral and bacterial pathogens in the lung. However, whether intestinal microbiota composition and associated changes in microbe-derived metabolites contribute to the risk of LRTI following upper respiratory tract viral infection remains unexplored in the setting of allo-HCT. Fecal samples from 360 allo-HCT patients were collected at the time of stem cell engraftment and subjected to deep, 16S ribosomal RNA gene sequencing to determine microbiota composition, and short-chain fatty acid levels were determined in a nested subset of fecal samples. The development of respiratory viral infections and LRTI was determined for 180 days following allo-HCT. Clinical and microbiota risk factors for LRTI were subsequently evaluated using survival analysis. Respiratory viral infection occurred in 149 (41.4%) patients. Of those, 47 (31.5%) developed LRTI. Patients with higher abundances of butyrate-producing bacteria were fivefold less likely to develop viral LRTI, independent of other factors (adjusted hazard ratio = 0.22, 95% confidence interval 0.04-0.69). Higher representation of butyrate-producing bacteria in the fecal microbiota is associated with increased resistance against respiratory viral infection with LRTI in allo-HCT patients.
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Project description:BACKGROUND:Predicting risk of premature death is one of the most basic tasks in medicine and public health, but has proven to be difficult over the long term even with the best prognostic models. One popular strategy has been to improve prognostic models with candidate genes and other novel biomarkers. However, the gains in predictive power have been modest and the costs have been high, leading to a demand for cost-effective alternatives. We conducted a proof-of-principle investigation to examine whether simple, cheap, and noninvasive paper-and-pencil measures of social class and personality phenotype could improve the performance of one of the most widely used prediction models for all-cause mortality, the Charlson Comorbidity Index (CCI). METHODS:We used data from baseline and 25-year mortality follow-up of the UK Health and Lifestyle Study cohort. In a subset of the cohort, we first identified 5 psychosocial factors highly predictive of mortality: income, education, type A personality, communalism (preference for the company of others), and "lie" scale (a measure of denial, putatively associated with ill health). We then examined the predictive performance of the CCI with and without these measures in a validation subsample. RESULTS:Across 5-, 10-, 15-, 20-, and 25-year time horizons, the psychosocially augmented CCI showed substantially better discrimination [area under the receiver-operating curves (95% confidence interval) from 0.83 (0.81-0.85) to 0.84 (0.83-0.86)] than the CCI [area under the receiver-operating curves from 0.74 (0.71-0.76) to 0.77 (0.76-0.79)]. These translated into net reclassification improvements from 27% (23%-31%) to 35% (32%-38%) of survivors and from 23% (17%-30%) to 34% (17%-30%) of decedents; and 23%-42% reductions in the Number Needed to Screen. Calibration improved at all time horizons except 25 years, where it was decreased. CONCLUSION:Widespread attempts to improve prognostic models might consider not only novel biomarkers, but also psychosocial questionnaire measures.
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