Eltrombopag combined with immunosuppressive therapy for pediatric severe aplastic anemia.

BACKGROUND: Severe aplastic anemia (SAA) is caused by immune-mediated destruction. Standard immunosuppressive therapy (IST) is effective but needs to be improved. METHODS: The data of patients with SAA and received IST were analyzed retrospectively to conducted this historical control study. RESULTS: A total of 115 SAA patients (60 males; median age of 5.77 years and median follow-up time of 45 months) were enrolled in this study. The complete response rates (CRR) of the eltrombopag group at 3 and 6 months were higher than the control group (30.3% vs.8.2% at 3 months; 50.0% vs. 10.2% at 6 months). The overall response rates (ORR) showed no differences. There were significant differences in the times from G-CSF, Red blood cell transfusion, and Platelet transfusion between the two groups. No difference in overall survival (OS), event-free survival (EFS), and relapse rate between two groups. There is no variable were associated with prognosis in both groups. CONCLUSION: Addition of eltrombopag to IST confers faster hematological response and higher early hematological response in pediatric SAA patients. IMPACT: Addition of eltrombopag to standard immunosuppressive therapy confers faster hematological response and higher early hematological response in pediatric severe aplastic anemia patients. Eltrombopag showed reliable safety but had no impact on long-term response and prognosis. This article is a historical controlled study consisting of 115 pediatric severe aplastic anemia patients and makes up for the lack of clinical data deficient on pediatric severe aplastic anemia with TPO-RA combined with IST.

Clinical characteristics of hepatitis-associated aplastic anemia in children.

To understand the current situation of hepatitis-related aplastic anemia (HAAA) in children, we analyzed the patients with HAAA admitted to our hospital in the past 5 years to understand the disease characteristics and prognosis. The clinical data of patients with HAAA admitted to our hospital from February 2017 to May 2022 were retrospectively analyzed. A total of 81 patients with HAAA, 56 males and 25 females. The median onset age was 5.9 years. The median time from hepatitis to occurrence of hemocytopenia was 30 days, and the median follow-up time was 2.77 years. There were 23 cases (28.5%) of severe aplastic anemia (SAA), 50 cases of very severe aplastic anemia (VSAA), and 8 cases of non-severe aplastic anemia (NSAA). At the beginning of the disease, cytotoxic T lymphocyte (CTL) was higher than normal in 60% of patients, and the median CD4/CD8 ratio was 0.2. As of follow-up, 72 children survived, 4 were lost, and 5 died. Thirty-four cases were treated with immunosuppressive therapy (IST), with a median follow-up time of 0.97 years. The total reaction rate was 73.5% (25/34), the complete reaction rate was 67.6% (23/34), and the nonreaction rate was 26.5% (9/34). Multivariate analysis suggested that co-infection was an independent risk factor affecting the efficacy of IST at 6 months, with an OR value of 16.76, 95% CI (1.23, 227.95), P=0.034. No independent influencing factors were found at the end of follow-up. The proportion of CTL cells in peripheral blood of children with HAAA is relatively increased, and IST is effective in 73.5% of children. Co-infection may prolongs the time to response to IST.

Cyclosporine Monotherapy in Pediatric Patients With Non-severe Aplastic Anemia: A Retrospective Analysis.

Objective: The management of children with non-severe aplastic anemia (NSAA) is undefined and the efficacies and benefits of immunosuppressive therapy remain inconsistent. The study aimed to investigate the efficacy of Cyclosporine (CsA) monotherapy for pediatric NSAA. Methods: Clinical data of children with NSAA who had been treated with CsA monotherapy at the outpatient department of Beijing Children's Hospital, Capital Medical University, National Children's Medical Center from January 2017 to March 2021 was collected retrospectively. Patients who had been treated <1 years until the end of follow-up were excluded. Transfusion-independent NSAA was further divided into moderate NSAA and mild NSAA according to the degree of cytopenia. Progression was defined as the development of transfusion-dependent AA or SAA and relapse was considered when treatment failed after initial response. Results: A total of 95 pediatric patients with NSAA were enrolled in this study with 49 (51.6%) patients confirmed as mild NSAA, 38 (40%) as moderate NSAA and 8 (8.4%) as transfusion-dependent NSAA. The median treatment time of CsA was 22 (12-44) months. The overall response rate (ORR) was 57.9%, with 30.5% CR and 27.4% PR. Unexpectedly, patients with mild NSAA acquired lowest ORR (46.9%), then patients with moderate NSAA (63.2%), while 8 patients who were transfusion-dependent all had an active response to CsA. The granulocyte and megakaryocyte response was 46.9 and 55.8% respectively, while the erythrocyte response rate was as low as 22.5%. Univariate analyses revealed that patients with lower platelet count and higher interleukin 10 level predict an active response to CsA while higher level of fetal hemoglobin (HbF) tended to be a negative factor. Data of Treg cells before and after 1 year's treatment was available in a total number of 40 patients. Paired comparison found that the percentage of Treg cells in CD4+ T cells was decreased after 1 year's treatment of CsA (6.78 ± 2.72 vs. 5.23 ± 2.06, P = 0.001),both in responders and non-responders. The degree of decline in Treg cells between two distinctive response groups had no significant difference (P>0.05). With a median follow-up time of 22 months, 10.9% of responders relapsed and maintained NSAA while 27.5% of non-responders progressed to SAA or became transfusion-dependent. The overall progression rate was 11.6%. Conclusion: CsA monotherapy had heterogeneous effects in the treatment of children NSAA Treatment approaches should be hierarchical and individual in clinical. Patients with lower platelet count and higher interleukin 10 level predicted an active response to CsA. While higher level of fetal hemoglobin (HbF) tended to be a negative factor. The percentage of Treg cells in CD4+ T cells was decreased broadly after treatment.

Living Preference Modifies the Associations of Living Arrangements With Loneliness Among Community-Dwelling Older Adults.

OBJECTIVES: Living arrangement has been reported to have a significant influence on feelings of loneliness in older adults, but their living preferences may confound the association. This study aimed to investigate whether the associations of living arrangements with loneliness differ in community-dwelling older adults according to different living preferences. METHODS: In the 2008/2009 (baseline) and 2011/2012 (follow-up) waves of the Chinese Longitudinal Healthy Longevity Survey, living arrangements [living with children mainly (LWC), living with spouse only (LWS), and living alone (LA)], living preferences [preferring living with children (PreLWC) and preferring living alone/only with spouse (PreLA)], and feelings of loneliness were assessed. The effect modifications of living preferences in the associations of living arrangements with loneliness were estimated using logistic regression models, and corresponding odds ratios (ORs) were calculated. RESULTS: Living preferences significantly modified the associations of living arrangements with loneliness at baseline (p for interaction = 0.009 for LWS and = 0.015 for LA). Compared with LWC, LWS was protective for loneliness only in the PreLA older adults at baseline (OR = 0.53, 95% CI = 0.45-0.64, p < 0.001), and LA was significantly associated with loneliness especially in the PreLWC older adults, compared with their PreLA counterparts (at baseline, ORs = 2.89 vs. 2.15; at follow-up, ORs = 1.68 vs. 1.51). CONCLUSION: Living preference modifies the associations of living arrangements with loneliness, and those who prefer living with children but live alone are more likely to feel lonely. It is recommended that living preferences should be considered when managing loneliness in community-dwelling older adults.

A Prospective Study on the Association Between Grip Strength and Cognitive Function Among Middle-Aged and Elderly Chinese Participants.

OBJECTIVE: To study the efficacy of grip strength (GS) as a predictor of cognitive function in a large, nationwide sample of Chinese participants aged 45 years and above. METHODS: We used data from three waves (W1, W2, and W3) fielded by the China Health and Retirement Longitudinal Study (CHARLS). Cognitive function was tested biennially and calculated using two categories: episodic memory and mental intactness. Demographics, health behaviors, and medical conditions were considered potential confounders. Using multivariate linear regression models (MLRMs), we examined the association between baseline GS (measure in W1) and cognitive function in W3. Using a generalized estimating equation (GEE), we examined baseline GS as a predictor of cognitive function change. RESULTS: Total 9,333 individuals (53.2% women), with a mean baseline episodic memory score of 6.5, mean baseline mental intactness score of 7.2, and aged over 45 years (mean age = 58.6), were selected. The mean follow-up time was 4.0 years (range: 3.3-5.0 years). Using MLRMs and comparing the lowest GS score with the highest baseline GS score, we observed a significant correlation with a higher global cognitive function in both women (ß = 1.061, p < 0.001) and men (ß = 1.233, p < 0.001). After adjusting baseline global cognition, the highest GS level was still statistically significant in both women (ß = 0.543, p < 0.05) and men (ß = 0.742, p < 0.001). GEE suggested that the participants in the highest GS quartile had better cognitive performance over time in both women (ß = 0.116, p = 0.030) and men (ß = 0.143, p = 0.008) than those in the lowest quartile. CONCLUSION: Higher baseline level of GS was significantly related to better cognitive function and slowed the rate of its decline. Thus, it is an independent predictor of better cognitive status in middle-aged and elderly Chinese.