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Trials Jun 2024Although hematopoietic stem cell transplantation provides the chances of survival for aplastic anemia patients, it is also related to many treatment-related physical and...
BACKGROUND
Although hematopoietic stem cell transplantation provides the chances of survival for aplastic anemia patients, it is also related to many treatment-related physical and psychological side effects that severely influence the quality of life. Exercise interventions have shown positive results in mixed hematology populations. The study aims to determine the effectiveness of exercise rehabilitation in improving the quality of life, fatigue, and physical function in these patients.
METHODS
The study will enroll a total of 82 aplastic anemia patients receiving hematopoietic stem cell transplantation. They will be randomly divided into two groups in a 1:1 ratio. The intervention group will participate in structured exercise rehabilitation (plus usual care), while control group participants will receive usual care. The exercise rehabilitation program will be performed from neutrophil and platelet engraftment until 100 days after transplantation. All outcomes will be measured at the following time points: the neutrophil and platelet engraftment (± 1day, T0), discharge from the transplantation module (± 1 day, T1), hospital discharge (± 1 day, T2), and 100 days post-transplantation (± 5 days, T3).
DISCUSSION
This study aims to assess the effectiveness of exercise rehabilitation for aplastic anemia patients receiving hematopoietic stem cell transplantation in a Chinese single center. It is particularly vital to conduct the studies in this population. Moreover, the evidence obtained from the study will provide evidence for future research and clinical practice to exercise in aplastic anemia patients.
TRIAL REGISTRATION
ChiCTR2200060762. Registered on May 2022, www.trialregister.nl/trial/7702.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Anemia, Aplastic; Quality of Life; Exercise Therapy; Randomized Controlled Trials as Topic; Treatment Outcome; Adult; Male; Adolescent; Female; Young Adult; Fatigue; Middle Aged; Time Factors; China; Recovery of Function
PubMed: 38840199
DOI: 10.1186/s13063-024-08197-4 -
AMIA Joint Summits on Translational... 2024The goal of this study was to analyze diagnostic discrepancies between emergency department (ED) and hospital discharge diagnoses in patients with congestive heart...
The goal of this study was to analyze diagnostic discrepancies between emergency department (ED) and hospital discharge diagnoses in patients with congestive heart failure admitted to the ED. Using a synthetic dataset from the Department of Veterans Affairs, the patients' primary diagnoses were compared at two levels: diagnostic category and body system. With 12,621 patients and 24,235 admission cases, the study found a 58% mismatch rate at the category level, which was reduced to 30% at the body system level. Diagnostic categories associated with higher levels of mismatch included aplastic anemia, pneumonia, and bacterial infections. In contrast, diagnostic categories associated with lower levels of mismatch included alcohol-related disorders, COVID-19, cardiac dysrhythmias, and gastrointestinal hemorrhage. Further investigation revealed that diagnostic mismatches are associated with longer hospital stays and higher mortality rates. These findings highlight the importance of reducing diagnostic uncertainty, particularly in specific diagnostic categories and body systems, to improve patient care following ED admission.
PubMed: 38827093
DOI: No ID Found -
SAGE Open Medicine 2024To observe the efficacy of haploidentcial peripheral blood stem cell transplantation combined with a single unrelated cord blood unit for severe aplastic anemia patients...
OBJECTIVE
To observe the efficacy of haploidentcial peripheral blood stem cell transplantation combined with a single unrelated cord blood unit for severe aplastic anemia patients with donor-recipient ABO incompatibility.
METHODS
This was a retrospective cohort study and data of 57 severe aplastic anemia patients underwent haploidentical stem cell transplantation from August 1, 2018 to February 28, 2022 in the First Affiliated Hospital of Xi'an Jiaotong University was retrospectively analyzed. All patients were divided into two groups, the donor-recipient ABO matched group (bone marrow+peripheral blood group) using haploidentical bone marrow and peripheral blood stem cells as grafts, and donor-recipient ABO mismatched group (cord blood+peripheral blood group), using unrelated cord blood and haploidentical peripheral blood stem cells as grafts. The differences of hematopoietic reconstitution, acute and chronic graft-versus-host disease, Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infection, and overall survival between the two groups were compared.
RESULTS
There were 30 cases in cord blood+peripheral blood group and 27 cases in bone marrow+peripheral blood group. One patient in bone marrow+peripheral blood group had primary graft failure, while other patients were successfully implanted. There were no significant differences of neutrophil and platelet recovery rates between two groups. The erythrocyte recovery time of cord blood+peripheral blood group was slower than that of bone marrow+peripheral blood group ( < 0.05). There was no significant difference of the incidence of graft-versus-host disease, CMV, EB virus infection and post-transplant lymphoproliferative disorders between two groups ( > 0.05). The incidence of grade III-IV acute graft-versus-host disease in cord blood+peripheral blood group was higher than that of bone marrow+peripheral blood group ( < 0.05). The incidence of intestinal graft-versus-host disease was higher in minor ABO-mismatched transplantation than that in major ABO-mismatched transplantation ( < 0.05). There was no significant difference of overall survival between two groups ( > 0.05).
CONCLUSION
These findings suggest that haploidentical peripheral blood stem cell transplantation combined with a single cord blood unit may be an alternative option for severe aplastic anemia patients with donor-recipient ABO incompatibility.
PubMed: 38826828
DOI: 10.1177/20503121241255807 -
Pediatric Research May 2024Severe aplastic anemia (SAA) is caused by immune-mediated destruction. Standard immunosuppressive therapy (IST) is effective but needs to be improved.
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.
PubMed: 38822136
DOI: 10.1038/s41390-024-03253-w -
World Journal of Stem Cells May 2024Aplastic anemia (AA) presents a significant clinical challenge as a life-threatening condition due to failure to produce essential blood cells, with the current...
BACKGROUND
Aplastic anemia (AA) presents a significant clinical challenge as a life-threatening condition due to failure to produce essential blood cells, with the current therapeutic options being notably limited.
AIM
To assess the therapeutic potential of ginsenoside Rg1 on AA, specifically its protective effects, while elucidating the mechanism at play.
METHODS
We employed a model of myelosuppression induced by cyclophosphamide (CTX) in C57 mice, followed by administration of ginsenoside Rg1 over 13 d. The investigation included examining the bone marrow, thymus and spleen for pathological changes hematoxylin-eosin staining. Moreover, orbital blood of mice was collected for blood routine examinations. Flow cytometry was employed to identify the impact of ginsenoside Rg1 on cell apoptosis and cycle in the bone marrow of AA mice. Additionally, the study further evaluated cytokine levels with enzyme-linked immunosorbent assay and analyzed the expression of key proteins in the MAPK signaling pathway western blot.
RESULTS
Administration of CTX led to significant damage to the bone marrow's structural integrity and a reduction in hematopoietic cells, establishing a model of AA. Ginsenoside Rg1 successfully reversed hematopoietic dysfunction in AA mice. In comparison to the AA group, ginsenoside Rg1 provided relief by reducing the induction of cell apoptosis and inflammation factors caused by CTX. Furthermore, it helped alleviate the blockade in the cell cycle. Treatment with ginsenoside Rg1 significantly alleviated myelosuppression in mice by inhibiting the MAPK signaling pathway.
CONCLUSION
This study suggested that ginsenoside Rg1 addresses AA by alleviating myelosuppression, primarily through modulating the MAPK signaling pathway, which paves the way for a novel therapeutic strategy in treating AA, highlighting the potential of ginsenoside Rg1 as a beneficial intervention.
PubMed: 38817329
DOI: 10.4252/wjsc.v16.i5.591 -
Blood Cells, Molecules & Diseases Jul 2024Immune dysregulation is crucial in the pathogenesis of acquired aplastic anaemia (aAA). There is paucity of data regarding correlation of baseline cytokine profile with...
BACKGROUND
Immune dysregulation is crucial in the pathogenesis of acquired aplastic anaemia (aAA). There is paucity of data regarding correlation of baseline cytokine profile with treatment response in aAA.
OBJECTIVE
Present prospective case-control study aimed to correlate the baseline cytokines in patients with aAA with the treatment response.
METHODS
Fifty-one patients with newly-diagnosed aAA > 13 years of either sex were enrolled over 1.5 years. Twenty age-and sex-matched healthy controls (HC) were also included. The cytokine profile (IL-2, 4, 6, 8, 10, 17, IFN-γ and TNF-α) in the peripheral blood plasma of aAA patients was performed at the baseline using cytometric bead analysis. The cytokine levels were compared with HC and correlated with response to immunosuppressive therapy (IST) at 3-months.
RESULTS
The median age of cases was 29 years (range,13-74). The cases had higher mean levels of IL2 (p = 0.326), IL4 (p = 0.038), IL6 (p = 0.000), IL10 (p = 0.002), TNF-α (p = 0.302), IFN-γ (p = 0.569) and IL-17 (p = 0.284) than the HC. The baseline levels of all the cytokines were higher (statistically non-significant) among responders (n = 13) than the non-responders (n = 14) to IST.
CONCLUSIONS
Baseline cytokine profile in patients with aAA might predict response to the IST. Larger studies are needed to validate our results.
Topics: Humans; Anemia, Aplastic; Male; Female; Adult; Cytokines; Middle Aged; Adolescent; Case-Control Studies; Young Adult; Aged; Prospective Studies; Severity of Illness Index; Immunosuppressive Agents; Treatment Outcome
PubMed: 38815307
DOI: 10.1016/j.bcmd.2024.102857 -
Pediatric Blood & Cancer Aug 2024
Topics: Humans; Fanconi Anemia; Leukemia, Erythroblastic, Acute; Abnormal Karyotype; Male; Cell Transformation, Neoplastic; Child; Child, Preschool
PubMed: 38814256
DOI: 10.1002/pbc.31098 -
British Journal of Haematology May 2024This study examines spermatogonial numbers in testicular samples from 43 prepubertal patients undergoing haematopoietic stem cell transplantation (HSCT). High-dose...
This study examines spermatogonial numbers in testicular samples from 43 prepubertal patients undergoing haematopoietic stem cell transplantation (HSCT). High-dose chemotherapy and/or radiation during HSCT can impact spermatogenesis requiring fertility preservation. Results show that 49% of patients have decreased and 19% severely depleted spermatogonial pool prior to HSCT. Patients with Fanconi anaemia exhibit significantly reduced spermatogonial numbers. Patients with immunodeficiency or aplastic anaemia generally present within the normal range, while results in patients with myelodysplastic syndrome or myeloproliferative neoplasm vary. The study emphasizes the importance of assessing spermatogonial numbers in patients with severe haematological diseases for informed fertility preservation decisions.
PubMed: 38810989
DOI: 10.1111/bjh.19572 -
Transplantation and Cellular Therapy May 2024Germline genetic testing for patients with severe aplastic anemia (SAA) is recommended to guide treatment, including the use of immunosuppressive therapy and/or...
Germline genetic testing for patients with severe aplastic anemia (SAA) is recommended to guide treatment, including the use of immunosuppressive therapy and/or adjustment of hematopoietic cell transplantation (HCT) modalities. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory condition often associated with cytopenias with autosomal recessive (AR) or X-linked recessive (XLR) inheritance. HLH is part of the SAA differential diagnosis, and genetic testing may identify variants in HLH genes in patients with SAA. The impact of pathogenic/likely pathogenic (P/LP) variants in HLH genes on HCT outcomes in SAA is unclear. In this study, we aimed to determine the frequency of HLH gene variants in a large cohort of patients with acquired SAA and to evaluate their association(s) with HCT outcomes. The Transplant Outcomes in Aplastic Anemia project, a collaboration between the National Cancer Institute and the Center for International Blood and Marrow Transplant Research, collected genomic and clinical data from 824 patients who underwent HCT for SAA between 1989 and 2015. We excluded 140 patients with inherited bone marrow failure syndromes and used exome sequencing data from the remaining 684 patients with acquired SAA to identify P/LP variants in 14 HLH-associated genes (11 AR, 3 XLR) curated using American College of Medical Genetics and Genomics/Association of Molecular Pathology (ACMG/AMP) criteria. Deleterious variants of uncertain significance (del-VUS) were defined as those not meeting the ACMG/AMP P/LP criteria but with damaging predictions in ≥3 of 5 meta-predictors (BayesDel, REVEL, CADD, MetaSVM, and/or EIGEN). The Kaplan-Meier estimator was used to calculate the probability of overall survival (OS) after HCT, and the cumulative incidence calculator was used for other HCT outcomes, accounting for relevant competing risks. There were 46 HLH variants in 49 of the 684 patients (7.2%). Seventeen variants in 19 patients (2.8%) were P/LP; 8 of these were loss-of-function variants. Among the 19 patients with P/LP HLH variants, 16 (84%) had monoallelic variants in genes with AR inheritance, and 3 had variants in XLR genes. PRF1 was the most frequently affected gene (in 8 of the 19 patients). We found no statistically significant differences in transplantation-related factors between patients with and those without P/LP HLH variants. The 5-year survival probability was 89% (95% confidence interval [CI], 72% to 99%) in patients with P/LP HLH variants and 70% (95% CI, 53% to 85%) in those with del-VUS HLH variants, compared to 66% (95% CI, 62% to 70%) in those without variants (P = .16, log-rank test). The median time to neutrophil engraftment was 16 days for patients with P/LP HLH variants and 18 days in those with del-VUS HLH variants or without variants combined (P = .01, Gray's test). No statistically significant associations between P/LP HLH variants and the risk of acute or chronic graft-versus-host disease were noted. In this large cohort of patients with acquired SAA, we found that 2.8% of patients harbored a P/LP variant in an HLH gene. No negative effects of HLH gene variants on post-HCT survival were noted. The small number of patients with P/LP HLH variants limits the study's ability to provide conclusive evidence; nonetheless, our data suggest that there is no need for special transplantation considerations for patients with SAA carrying P/LP variants.
PubMed: 38810947
DOI: 10.1016/j.jtct.2024.05.017 -
The American Journal of Tropical... May 2024Human strongyloidiasis is a potentially life-threatening parasitic disease among immunocompromised hosts. We aim to determine the factors and mortality associated with...
Human strongyloidiasis is a potentially life-threatening parasitic disease among immunocompromised hosts. We aim to determine the factors and mortality associated with disseminated strongyloidiasis. We conducted a U.S.-based multicenter retrospective cohort study to determine 90-day clinical outcomes for people diagnosed with Strongyloides infection in the TriNetX patient database. We identified adult patients with the International Classification of Diseases (10th revision, clinical modification) code for Strongyloides infection (B78) or a positive Strongyloides IgG antibody test and captured outcomes at 90 days. We identified 5,434 patients with strongyloidiasis, of whom 48 had disseminated strongyloidiasis for 0.9% prevalence of disseminated disease. Systemic connective tissue disorders, pulmonary eosinophilia, liver cirrhosis, blood disorders (monoclonal gammopathy, aplastic anemia, and lymphoid malignancy), malnutrition, alcohol use disorder, and transplantation status were frequent in patients with disseminated disease. Mortality was significantly higher in people with disseminated disease at 30 days (21%). The 90-day risk of hospitalization, bacteremia, and acute respiratory distress syndrome (ARDS) was higher in those with disseminated infection. People with disseminated strongyloidiasis had a heightened risk of hospitalization, bacteremia, acute respiratory distress syndrome, and mortality. The population at risk for severe strongyloidiasis infection is evolving, reflecting conditions in which glucocorticoids or additional immunosuppressive medications are commonly used for treatment.
PubMed: 38806043
DOI: 10.4269/ajtmh.23-0863