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Revue Medicale Suisse Jun 2024Aplastic anemia is a rare disease with a large differential diagnosis, including neoplastic origin as well as congenital bone marrow failure syndromes. Investigations...
Aplastic anemia is a rare disease with a large differential diagnosis, including neoplastic origin as well as congenital bone marrow failure syndromes. Investigations must be quick and precise. Treatment depends on the patient's age and consists of immunosuppression treatment or allogeneic bone marrow transplantation. Because of the risk of progression to other hematological diseases, a close specialized follow-up is recommended.
Topics: Humans; Anemia, Aplastic; Diagnosis, Differential; Bone Marrow Transplantation; Immunosuppressive Agents
PubMed: 38938138
DOI: 10.53738/REVMED.2024.20.880.1271 -
Clinics and Research in Hepatology and... Jun 2024The majority of indeterminate pediatric acute liver failure (PALF) cases are secondary to immune dysregulation, labeled activated T-cell hepatitis (TC-Hep). We aimed to...
BACKGROUND AND AIMS
The majority of indeterminate pediatric acute liver failure (PALF) cases are secondary to immune dysregulation, labeled activated T-cell hepatitis (TC-Hep). We aimed to describe a cohort of children with acute severe hepatitis and PALF and define how clinical immune labs may help identify the TC-Hep group.
METHODS
Retrospective review of children with acute hepatitis and PALF between March 2020 and August 2022. Patients were classified as known diagnosis, indeterminate hepatitis (IND-Hep), or TC-Hep (defined by liver biopsy with predominant CD8 T-cell inflammation or development of aplastic anemia).
RESULTS
124 patients were identified: 83 with known diagnoses, 16 with TC-Hep, and 25 with IND-Hep. Patients with TC-Hep had significantly increased median total bilirubin levels (7.5 mg/dL (IQR 6.8-8.9) vs 1.5 mg/dL (IQR 1.0-3.6), p<0.0001), soluble interleukin-2 receptor levels (4512 IU/mL (IQR 4073-5771) vs 2997 IU/mL (IQR 1957-3237), p=0.02), and percent of CD8+ T-cells expressing perforin (14.5% (IQR 8.0-20.0) vs 1.0% (IQR 0.8-1.0), p=0.004) and granzyme (37.5% (IQR 15.8-54.8) vs 4.0% (IQR 2.5-5.5), p=0.004) compared to IND-Hep patients. Clinical flow cytometry showed that TC-Hep patients had significantly increased percent CD8+ T cells (29.0% (IQR 24.5-33.5) vs 23.6% (IQR 19.8-25.8), p=0.04) and HLA-DR+ (16.0% (IQR 14.5-24.5) vs 2.7 (1.8-5.3), p<0.001) compared to IND-Hep patients indicative of increase in CD8+ T cells that are activated.
CONCLUSIONS
Peripheral blood clinical immune studies demonstrate increased markers of CD8 T-cell activation, proliferation, and cytotoxic function for TC-Hep patients. These readily available immune function labs can be used to help distinguish patients with TC-Hep from those with other causes. This provides a non-invasive tool for early detection of potential TC-Hep before progression to liver failure.
PubMed: 38936769
DOI: 10.1016/j.clinre.2024.102407 -
Cureus May 2024Imatinib is a tyrosine kinase inhibitor (TKI) and is a commonly used medication for treatment of chronic myelogenous leukemia (CML). Aplastic anemia is a very uncommon...
Imatinib is a tyrosine kinase inhibitor (TKI) and is a commonly used medication for treatment of chronic myelogenous leukemia (CML). Aplastic anemia is a very uncommon complication of Gleevec, and only a few cases are reported in the literature. We present a case of a 63-year-old Asian female who was initiated on imatinib for treatment of CML with good response in cell counts. Four months after Gleevec initiation, the patient was admitted to the hospital with extreme fatigue and noted to have severe pancytopenia. Patient received multiple blood transfusions. Finally, the patient underwent bone marrow biopsy, which showed concern for aplastic anemia with marked hypocellular bone marrow. Gleevec was held, blood counts were monitored, and supportive care was given. Patient had slow recovery of her blood counts. There remains scarcity of data on this topic and no criteria exist to predict the myelosuppression with TKI therapy. Our case report aims to reemphasize the need for increased research on myelosuppression with TKI therapy.
PubMed: 38933639
DOI: 10.7759/cureus.61176 -
Journal of Medical Virology Jun 2024The most prevalent malignancy that complicates both adult and pediatric solid organ transplantation is post-transplant lymphoproliferative disorder (PTLD). This study...
The most prevalent malignancy that complicates both adult and pediatric solid organ transplantation is post-transplant lymphoproliferative disorder (PTLD). This study aimed to analyze the clinical and pathological characteristics, treatments, and outcomes of Epstein-Barr virus (EBV) DNAemia and PTLD in pediatric liver transplant recipients. A retrospective chart review was performed on 112 patients less than 18 years of age who underwent isolated orthotopic liver transplantation (OLT) between 2010 and 2022 at Ege University Children's Hospital. Data gathered for 1-year post-OLT included age at OLT, EBV, immunoglobulin (Ig)M/IgG status of the donor and recipient, indication for OLT, induction regimen, all immunosuppression levels, date and result of EBV polymerase chain reaction testing, rejection episodes documented by liver biopsy, and the development of PTLD. Forty-nine patients (43.75%) developed EBV DNAemia (median interval from surgery: 2 months, min-max: 2-36), of which 43 (87.8%) grafts came from living donors, and 6 (12.2%) came from deceased donors. Nine (18.4%) patients died during follow-up, and eight (16.3%) developed PTLD. Of these 8 patients; five patients developed EBV-related disease, one child developed hemophagocytic lymphohistiocytosis, one developed aplastic anemia, and one child developed B cell lymphoma. When PTLD patients and without-PTLD patients were compared, pediatric intensive care unit hospitalization, abnormal bone marrow biopsy findings, lymphadenopathy, age at diagnosis of EBV DNAemia, EBV viral load, tacrolimus (FK 506) pre-infection, were higher and tacrolimus 1-month levels were lower in patients with PTLD (p < 0.05). In logistic regression analysis, we showed that the age at diagnosis of EBV DNAemia was significantly higher in children with PTLD (p = 0.045; OR: 1.389; 95% CI: 1.007-1.914). PTLD is a rare but severe complication associated with EBV after OLT. This study demonstrated that PTLD is associated with older age, higher tacrolimus blood levels before EBV DNAemia, and higher peak EBV viral load at 1 month of EBV DNAemia.
Topics: Humans; Lymphoproliferative Disorders; Liver Transplantation; Retrospective Studies; Child; Child, Preschool; Male; Female; Epstein-Barr Virus Infections; DNA, Viral; Infant; Herpesvirus 4, Human; Adolescent
PubMed: 38932460
DOI: 10.1002/jmv.29767 -
Children (Basel, Switzerland) Jun 2024Shwachman Diamond Syndrome (SDS) is a multi-system disease characterized by exocrine pancreatic insufficiency with malabsorption, infantile neutropenia and aplastic... (Review)
Review
Lethal Complications and Complex Genotypes in Shwachman Diamond Syndrome: Report of a Family with Recurrent Neonatal Deaths and a Case-Based Brief Review of the Literature.
Shwachman Diamond Syndrome (SDS) is a multi-system disease characterized by exocrine pancreatic insufficiency with malabsorption, infantile neutropenia and aplastic anemia. Life-threatening complications include progression to acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), critical deep-tissue infections and asphyxiating thoracic dystrophy. In most patients, SDS results from biallelic pathogenic variants in the gene, different combinations of which contribute to heterogenous clinical presentations. Null variants are not well tolerated, supporting the theory that the loss of SBDS expression is likely lethal in both mice and humans. A novel complex genotype (SBDS:c.[242C>G;258+2T>C];[460-1G>A]/WFS1:c.[2327A>T];[1371G>T]) was detected in a family with recurrent neonatal deaths. A female neonate died three hours after birth with hemolytic anemia, and a male neonate with severe anemia, thrombocytopenia and neutropenia succumbed on day 40 after infection. A subsequent review of the literature focused on fatal complications, complex SBDS genotypes and/or unusual clinical presentations and disclosed rare cases, of which some had unexpected combinations of genetic and clinical findings. The impact of pathogenic variants and associated phenotypes is discussed in the context of data sharing towards expanding scientific expert networks, consolidating knowledge and advancing an understanding of novel underlying genotypes and complex phenotypes, facilitating informed clinical decisions and disease management.
PubMed: 38929284
DOI: 10.3390/children11060705 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024Studies have found that 1/3 patients with acquired aplastic anemia have shortened telomere length, and the shorter the telomere, the longer the disease course, the more... (Review)
Review
Studies have found that 1/3 patients with acquired aplastic anemia have shortened telomere length, and the shorter the telomere, the longer the disease course, the more prone to relapse, the lower the overall survival rate, and the higher the probability of clonal evolution. The regulation of telomere length is affected by many factors, including telomerase activity, telomerase-related genes, telomere regulatory proteins and other related factors. Telomere shortening can lead to genetic instability and increases the probability of clonal evolution in patients with acquired aplastic anemia. This article reviews the role of telomere in the clonal evolution of acquired aplastic anemia and factors affecting telomere length.
Topics: Anemia, Aplastic; Telomere Shortening; Clonal Evolution; Survival Rate; Recurrence; Telomere Homeostasis; Telomerase; Genomic Instability; Humans
PubMed: 38926996
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.048 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024To explore the efficacy and safety of haploidentical hematopoietic stem cell transplantation combined with umbilical cord blood infusion for the treatment of aplastic...
OBJECTIVE
To explore the efficacy and safety of haploidentical hematopoietic stem cell transplantation combined with umbilical cord blood infusion for the treatment of aplastic anaemia in children.
METHODS
Nine cases of children with aplastic anaemia treated with umbilical cord blood combined with haploidentical hematopoietic stem cell transplantation at the People's Hospital of Henan University of Chinese Medicine from January 1, 2021 to September 15, 2023 with a median age of 11(2-13) years and a median follow up of 18(7.5-21) months were included, and the clinical data were retrospectively analyzed. Hematopoiesis reconstitution, the incidence of graft-versus-host disease(GVHD), infections and survival of the patients were analyzed.
RESULTS
All 9 children were successfully implanted. The median time to neutrophil and platelet implantation was 11.11±1.27 d and 12.44±3.36 d, respectively. One case developed acute gastrointestinal GVHD of degree I, which was improved after treatment, and the patient developed superficial gastritis and chronic gastrointestinal GVHD at a later stage, which is currently under clinical follow-up. Acute GVHD of II-IV degree was 0%. Hemorrhagic cystitis in 3 cases, CMV infection in 5 cases and bacterial and fungal infections in 5 cases improved with symptomatic treatment.All 9 children demonstrated complete donor chimerism within 1 month after transplantation, at two years of follow-up, all nine children survived without recurrence or development of grade II-IV GVHD, and there were no children with transplant-related deaths.
CONCLUSION
Haploidentical hematopoietic stem cell transplantation combined with umbilical cord blood transfusion for aplastic anaemia in children has a low incidence and mild degree of GVHD, with significant efficacy, and can be used as a therapeutic option for children without an HLA full donor chimeric match.
Topics: Humans; Anemia, Aplastic; Child; Hematopoietic Stem Cell Transplantation; Child, Preschool; Graft vs Host Disease; Retrospective Studies; Adolescent; Cord Blood Stem Cell Transplantation; Fetal Blood; Transplantation, Haploidentical; Male; Female
PubMed: 38926985
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.037 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024To analyze the efficacy and influencing factors of cyclosporine (CsA) alone in the treatment of children with acquired aplastic anemia (AA).
OBJECTIVE
To analyze the efficacy and influencing factors of cyclosporine (CsA) alone in the treatment of children with acquired aplastic anemia (AA).
METHODS
The clinical data of children diagnosed with AA and treated with CsA alone from January 1, 2016 to December 31, 2020 in the Children's Hospital of Chongqing Medical University were collected, and the efficacy and influencing factors of CsA treatment were evaluated.
RESULTS
Among the 119 patients, there were 62 male and 57 female, with a median age of 7 years and 1 month. There were 45 cases of very severe AA (VSAA), 47 cases of severe AA (SAA), and 27 cases of non-severe AA (NSAA). At 6 months after treatment, the efficacy of VSAA was lower than that of SAA and NSAA, and there was a statistical difference ( < 0.01). 6 cases died early, 16 cases relapsed, 2 cases progressed to AML and ALL. The results of univariate analysis showed that the high proportion of lymphocyte in the bone marrow at 6 months was an adverse factor for the efficacy of CsA, while high PLT count was a protective factor ( =0.008, =0.002). The ROC curve showed that the cut-off values of PLT count and the proportion of bone marrow lymphocyte at 6 months were 16.5×10 /L, 68.5%, respectively. Multivariate analysis showed that the high proportion of lymphocyte in bone marrow at 6 months was an independent adverse factor for IST ( =0.020, =0.062), and high PLT count was a protective factor ( =0.044, =1.038). At 3 months of treatment, CsA response and NSAA were the risk factor for recurrence ( =0.001, 0.031).
CONCLUSION
The efficacy of NSAA was higher than that of SAA and VSAA after 6 months of treatment with CsA alone. A high PLT count at the initial diagnosis was a good factor for the effectiveness of CsA, and a high proportion of bone marrow lymphocyte was an unfavorable factor. CsA response at 3 months and NSAA were risk factors for recurrence.
Topics: Humans; Anemia, Aplastic; Cyclosporine; Female; Male; Child; Treatment Outcome; Platelet Count; Immunosuppressive Agents; Child, Preschool; Adolescent; Bone Marrow
PubMed: 38926977
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.029 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024To investigate the expression level and clinical correlation of gene cluster () in different types of anemia.
OBJECTIVE
To investigate the expression level and clinical correlation of gene cluster () in different types of anemia.
METHODS
The peripheral blood of patients with aplastic anemia (AA), myelodysplastic syndrome (MDS) and diffuse large B-cell lymphoma (DLBCL) who had been diagnosed with anemia for the first time and after chemotherapy were collected. The expression levels of and were measured by RT-qPCR, and the correlation between the expression levels of and and routine laboratory indexes was analyzed by Spearman correlation analysis.
RESULTS
The expression levels of and in the peripheral blood of AA and MDS patients were significantly lower than those in normal controls (all < 0.01). No statistical differences were observed in the expression level of in three subgroups of DLBCL patients ( >0.05), while the expression level of in peripheral blood of three subgroups of DLBCL patients were significantly higher than those in normal controls (all < 0.05). Correlation analysis showed that the expression levels of and in AA patients were positively correlated with red blood cell distribution width-coefficient of variation (RDW-CV) ( =0.629, 0.574). There were no significant correlations between the expression levels of and and laboratory parameters in MDS and DLBCL patients.
CONCLUSION
Different types of anemia disorders have varying levels of and expression, which is anticipated to develop into a secondary diagnostic and differential diagnostic indicator for clinical anemia diseases.
Topics: Humans; MicroRNAs; Myelodysplastic Syndromes; Lymphoma, Large B-Cell, Diffuse; Anemia, Aplastic; Anemia; Multigene Family
PubMed: 38926974
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.026 -
Hamostaseologie Jun 2024This review summarizes the rationale and current data on the use of thrombopoietin receptor agonists (TPO-RAs) for treating severe thrombocytopenia in infants, children,...
This review summarizes the rationale and current data on the use of thrombopoietin receptor agonists (TPO-RAs) for treating severe thrombocytopenia in infants, children, and adolescents. It focuses on substances that have been approved by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) for pediatric patients. Romiplostim and eltrombopag are already established as second-line treatment for persistent or chronic immune thrombocytopenia (ITP). As in adults, TPO-RAs are currently also evaluated in severe aplastic anemia (SAA), chemotherapy-induced thrombocytopenia (CIT), myelodysplastic syndromes (MDS), and poor engraftment after hematopoietic stem cell transplantation in pediatric and adolescent patients. Moreover, studies on the implication of TPO-RA in treating rare inherited thrombocytopenias, such as Wiskott-Aldrich syndrome (WAS), congenital amegakaryocytic thrombocytopenia (CAMT), or -associated thrombocytopenia, deserve future attention. Current developments include testing of avatrombopag and lusutrombopag that are approved for the treatment of thrombocytopenia associated with chronic liver disease (CLD) in adult patients. In pediatric and adolescent medicine, we expect in the near future a broader use of TPO-RAs as first-line treatment in primary ITP, thereby considering immunomodulatory effects that increase the rate of sustained remission off-treatment, and a selective use in rare inherited thrombocytopenias based on current clinical trials.
PubMed: 38925157
DOI: 10.1055/a-2247-4209