Primary immune thrombocytopenia in children according to contemporary definitions

BackgroundPrimary immune thrombocytopenia (ITP) is one of the most common hematologic disorders in pediatric population. In 2009 the new unified terminology regarding: definition, clinical classification of the disease and response to treatment was proposed. The main study objective was the comparative analysis of clinical aspects of primary ITP in children regarding the contemporary definitions and historical criteria.MethodsData were collected through medical chart review of subjects identified from hospitalization records (Pediatrics, Hematology and Oncology Department) from the period of 2002–2011.ResultsData of 209 subjects were analyzed. According to recent definitions 206/209 patients (98.6%) could be defined. Using the historical criteria 86.12% were classified as acute and 13.88% as chronic ITP. Newly diagnosed primary immune thrombocytopenia was confirmed in 166/206 cases, persistent ITP in 20/206, and chronic ITP in 20/206 of subjects. Depending on applied criteria we noticed significant differences in acute ITP patient number. Regardless of adjusted definitions, the response rates were higher among treated patients (

Transborder program of allogeneic hematopoietic cell transplantations from unrelated donors for Ukrainian children between 2015–2020 in Bydgoszcz

Introduction: The aim of this study was the analysis of the organizational aspects, treatments and outcomes of the program of allogeneic hematopoietic stem cell transplantations (HCT) from unrelated donors for children from Ukraine in the Transplant Center in Bydgoszcz, Poland over the period 2015–2020. Material and methods: Patients from Ukraine were referred via email by parents or by the Tabletochki Charity Foundation based in Kyiv directly to transplant physicians or to the Medical Office of Jurasz University Hospital 1 in Bydgoszcz. Results: Overall, 28 allo-matched unrelated donor-HCTs in 22 patients were performed. Children were diagnosed for malignant (n = 19) or non-malignant (n = 3) diseases. Most of the children were in advanced stages of the disease. The cumulative probabilities of hematological engraftment measured by neutrophil and platelet recovery were 90.6% and 77.3%, respectively. The cumulative incidence of acute graft-versus-host disease ≥2° and extensive chronic graft-versus-host disease were 40.9% and 27.7%, respectively. Overall, 11/19 patients with malignant diseases and 1/3 with non-malignant diseases were alive at the end of a median follow-up of 1.5 (range 0.1–6.5) years. Overall survival (OS) for all patients was 0.51 ± 0.11. Patients with malignancies at transplant standard risk had OS = 0.83 ± 0.15, while those with transplant high-risk had OS = 0.34 ± 0.15 (p = 0.025). A total of 10/22 children died. The treatment-related mortality rate was 6/22 (27.3%). The overall relapse rate among children with malignancies was 4/19 (21%). Conclusions: The program of transborder transplants for children from Ukraine was an important factor in international co-operation contributing to the establishment of a program of transplants from unrelated donors for children in Ukraine. The outcome was positive for more than half of the children referred to the program

Letermovir use in children after hematopoietic cell transplantation: summary of reported data

Introduction: Letermovir (LMV) is approved for primary prophylaxis of cytomegalovirus infection (CMVi) in CMV-seropositive adult patients undergoing allogeneic hematopoietic stem cell transplantation. However, it is not registered for CMVi preemptive treatment, CMVi secondary prophylaxis, or the treatment of CMV disease. There is very limited data regarding LMV’s use in pediatric patients, as it has not been approved so far as any kind of treatment in children, with its use remaining off label. The aim of this study was to summarize reported data on the efficacy and safety of LMV in pediatric patients. Material and methods: Studies and case reports regarding LMV’s use in pediatric patients were searched in PubMed. Results: Overall, nine reports that fulfilled the search criteria, published between 2019 and 2022, were found and analyzed. The total number of cases involved in research was 46 with patient age ranging from 2–19 years; one child was counted twice due to another transplant. The most common serostatus of donor/recipient was D+/R+ (47%), followed by D–/R+ (42%), then D+/R– (2%), and then unknown (9%). Most patients had received the transplant from a matched unrelated donor (40%). There were 47 incidents of LMV administration as CMV management strategy. The analyzed patients received LMV as primary prophylaxis (74%), secondary prophylaxis (15%), pre-emptive therapy (6%), or treatment of CMV disease (4%). One patient received LMV as a treatment and then as a secondary prophylaxis. In 44/46 (95.6%) cases, no symptomatic CMVi occurred during LMV administration, with only transient CMV DNA-emia present on rare occasions. Conclusion: The use of LMV is safe in pediatric patients

Gene expression analysis in the pathogenesis of chronic immune thrombocytopenia in children

BackgroundA complex multifactorial dysregulation of immune system, including cytokines and autoantibodies production, and also proteins modification underlay the primary mechanism of immune thrombocytopenia (ITP). Specific genetic profile of ITP patients is presumed, especially those with a long and complex natural history of the disease.Aim of the studyGene expression analysis of VNN1 and PPARγ in children with immune thrombocytopenia.Materials and methodsCandidate genes were identified with microarray cDNA procedure. For the validation of VNN1 and PPARγ expression changes we used qRT-PCR performed comparatively in samples of newly diagnosed ITP (ndITP, n=16), chronic ITP (cITP, n=8) and patients without thrombocytopenia (n=5).ResultsWe analyzed the data of patients, followed for at least 12 months after ITP diagnosis. No significant differences of VNN1 expression profile were found in between groups (p>0.05). Lower signatures of mean PPARγ normalized expression values were noticed in chronic ITP patients in contrast to newly diagnosed ITP subjects (p=0.009). Differences between VNN1/PPARγ ratio values found in ndITP group comparing to subjects with progression to cITP were close to statistical significance (p=0.054).ConclusionsAnalysis of the VNN1 and PPARγ expression profiles utility in children diagnosed with ITP requires further investigation

Coagulopathy and thromboembolism in children with COVID-19 – pathophysiology, thrombotic risk, clinical manifestations and management

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the beginning of the pandemic, it has been generally accepted that children infected with SARS-CoV-2 either stay asymptomatic or present benign symptoms. Yet SARS-CoV-2 is widely known to cause serious consequences in children and adolescents. Complications may develop during infection, several weeks afterwards, or in the course of multisystem inflammatory syndrome in children (MIS-C). MIS-C manifests with fever, gastrointestinal, cardiovascular and/or neurological symptoms. Moreover, thromboembolism is a relatively common complication of COVID-19 and MIS-C. The purpose of this work was to review current reports on thromboembolic complications among children who underwent SARS-CoV-2 infection. Among the published cases of MIS-C, thromboembolic incidents ranged from 1.4% to 6.5%, taking the form of a brain infarct, deep vein thrombosis, pulmonary embolism, or splenic infarct. Several mechanisms leading to thrombosis in COVID-19 in children are considered. The development of acute infection in the lungs results in local clot formation in the pulmonary microcirculation, leading to perfusion disturbances. ADAMTS13 activity is also mildly reduced in patients infected with SARS-CoV-2, increasing the risk of microthrombosis. COVID-19-associated coagulopathy is characterized by elevated D-dimers and fibrinogen levels. Significantly increased D-dimers probably represent activation of coagulation caused by viremia and cytokine storm, as well as possible organ dysfunction. The treatment of thromboembolism in children includes low and high molecular weight heparins and acetylsalicylic acid. Pediatricians should be aware of the possible multiple complications associated with COVID-19 in children, including thromboembolic incidents

Sclerodermatous manifestation of chronic graft versus host disease: therapy challenges

Chronic graft versus host disease (cGHVD) is one of the most serious complications after allogeneic hematopoietic cell transplantation (allo-HCT). It varies in between patients, often leading to systemic and functional limitations. It can be challenging considering the heterogeneity of patients. The objective of this paper is to present clinical aspects of sclerodermatous manifestation of cGVHD as a complication of allo-HCT in pediatric patients. We diagnosed three patients with different sclerodermatous skin involvement and cGVHD features. The treatment applied varied among patients and was based on current available standards of care. We analyzed effectiveness of systemic steroid therapy, extracorporeal photopheresis and ruxolitinib. In conclusion, all patients achieved improvement in skin leasions and quality of life, based on the individualized treatment approach

Eltrombopag use in chronic immune thrombocytopenia of childhood: results from nationwide therapeutic program

BackgroundThrombopoietin receptor agonists have been repeatedly confirmed to be safe, efficient, and well tolerated in pediatric patients with chronic immune thrombocytopenia (cITP). Material and methodsIn this report, we present data summarizing the Polish experience of the use of eltrombopag in cITP patients, refractory to standard first-line care. Our analysis was based on clinical and epidemiological data from the Nationwide Therapeutic Program 2018–2020. Quality of the response to the eltrombopag treatment was defined according to the International Consensus Guidelines as follows: complete response (CR) defined as platelet count (PLT) ≥100 × 10/L and absence of bleeding; response (R) defined as PLT ≥30 × 10/L and at least two-fold increase in the baseline count and absence of bleeding. ResultsWe evaluated 60 patients (33 boys and 27 girls) with chronic and refractory ITP. Median age at beginning of treatment was 9.5 years. Median PLT at the first eltrombopag administration was 30 × 10/L. The median follow-up was 7 months (range, 3–22 months). After 1 week of treatment, response (R) was noted in 53.3% (95% confidence interval [CI]: 40.7%–66.0%) patients, and complete response (CR) was seen in 21.6% (95% CI: 11.2%–32.1%). We evaluated the long-term duration of the response and found that it was obtained in 84.4% (95% CI: 71.8%–97.0%) and 88.9% (95% CI: 77.0%–100%) of patients after 6 and 12 months, respectively, of eltrombopag therapy, while CR was reached, respectively, in 46.9% (95% CI: 29.6%–64.2%) and 29.6% (95% CI: 12.4%–46.9%) patients. No serious adverse events were reported. ConclusionOur data support the safety and efficacy of eltrombopag use in cITP pediatric patients