Pediatric Hematology/Oncology and Immunopathology最新文献

{"title":"A successful second allogeneic hematopoietic stem cell transplantation from an alternative donor in a patient with loss of HLA heterozygosity relapse of juvenile myelomonocytic leukemia: case series analysis","authors":"L. A. Tsvetkova, A. A. Osipova, A. V. Evdokimov, P. V. Kozhokar, Zh. Z. Rakhmanova, I. M. Barkhatov, O. V. Paina, O. S. Epifanovskaya, E. V. Babenko, N. E. Ivanova, D. V. Kozlov, T. L. Gindina, T. А. Bykova, E. V. Semenova, L. S. Zubarovskaya","doi":"10.24287/1726-1708-2023-22-3-36-42","DOIUrl":"https://doi.org/10.24287/1726-1708-2023-22-3-36-42","url":null,"abstract":"The development of inhibitory antibodies against FVIII is the most serious complication associated with the use of FVIII concentrates in hemophilia A patients. There is a need for more research on measures that could reduce the risk of inhibitor formation in previously untreated patients (PUPs) with severe hemophilia A. The purpose of this study was to determine the effectiveness of the prevention of clotting inhibitor development in PUPs (or minimally treated patients) with severe hemophilia A by administering plasma-derived factor VIII concentrate (pdFVIII) at a dose of 25 IU/kg once a week for a year. The study was approved by the Independent Ethics Committee and the Scientific Council of the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology (the Republic of Belarus). Between 2010 and 2022, 56 boys were newly diagnosed with severe hemophilia A. Twenty-one of them received pdFVIII as on-demand treatment to stop bleeding (Group 1). Thirty-five boys received pdFVIII at a dose of 25 IU/kg body weight once a week during the first 50 weeks of treatment for the prevention of inhibitor development (Group 2). The administration of pdFVIII at a dose of 25 IU/kg once a week in the PUPs (or minimally treated patients) contributed to a decrease in the cumulative incidence of inhibitors to 15.9 ± 7.7% (4 out of the 35 patients who had been treated prophylactically) compared with 43.7 ± 11.8% (8 out of the 21 patients who had received hemostatic therapy to stop bleeding) (log-rank test, p = 0.041). Thus, the administration of pdFVIII concentrate at a dose of 25 IU/kg once a week for the first 50 weeks of treatment lead to a decrease (p = 0.009) in the cumulative incidence of inhibitors against the administered coagulation factor VIII to 15.9 ± 7.7%.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"64 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134935717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The efficacy of the TRK inhibitor entrectinib in patients with extracranial <i>NTRK</i> fusion-positive tumors","authors":"T. V. Stradomskaya, A. M. Suleymanova, D. M. Konovalov, A. E. Druy, A. V. Panfyorova, E. V. Preobrazhenskaya, N. A. Andreeva, G. B. Sagoyan, M. V. Teleshova, L. A. Smirnova, O. S. Zacarinnaya, T. V. Shamanskaya, N. S. Grachev, M. V. Rubanskaya, K. I. Kirgizov, E. N. Imyanitov, S. R. Varfolomeeva, D. Yu. Kachanov","doi":"10.24287/1726-1708-2023-22-3-104-120","DOIUrl":"https://doi.org/10.24287/1726-1708-2023-22-3-104-120","url":null,"abstract":"Somatic translocations involving the NTRK genes occur in 0.34–2.2% of all malignant neoplasms in children. TRK inhibitors whose efficacy has been demonstrated in prospective clinical studies expand treatment options for patients with solid tumors harboring NTRK gene rearrangements. The aim of our study was to summarize the first Russian experience with the use of the TRK inhibitor entrectinib in patients with extracranial NTRK fusion-positive solid tumors included in the compassionate use program. This study was approved by the Independent Ethics Committee and the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The study included 8 patients who had been treated at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology and the N.N. Blokhin National Medical Research Center of Oncology. The main criteria for inclusion in the compassionate use program were a confirmed rearrangement of either NTRK1/2/3 genes in a solid tumor in patients with unresectable disease for whom no effective standard systemic therapy was available, progressive or recurrent disease during therapy prescribed according to the established diagnosis, risk group and risk stratification criteria, and the infeasibility of non-mutilating radical surgery. The median age at diagnosis was 4.3 months (range 1.2–83.6). The male to female ratio was 1:1. The primary site distribution was as follows: head and neck (n = 6; 75%), chest wall (n = 1; 12.5%), pelvis (n = 1; 12.5%). None of the patients had regional lymph node involvement or distant metastases at diagnosis. The distribution by histology (according to histopathology reports) was as follows: infantile fibrosarcoma (n = 4; 50%), undifferentiated round cell sarcoma, low-grade (n = 1; 12.5%), undifferentiated spindle cell sarcoma, high-grade (n = 1; 12.5%), NTRK-rearranged spindle cell sarcoma, low-grade (n = 1; 12.5%), spindle cell tumor associated with an NTRK rearrangement (n = 1; 12.5%). Immunohistochemistry (IHC) with a pan-Trk monoclonal antibody was performed in 7/8 (87.5%) patients. Pan-Trk IHC was positive in 4/7 (57%) patients. Rearrangements in the NTRK1 and NTRK3 genes were confirmed in all the patients. The final methods used for the detection of fusion transcripts were as follows: reverse transcription polymerase chain reaction (n = 4; 50%) and RNA-based next-generation sequencing (n = 4; 50%). NTRK1 and NTRK3 gene translocations were detected in 3/8 (37.5%) and 5/8 (62.5%) patients, respectively. The following fusion transcripts were identified: ETV6::NTRK3 (n = 4), DIP2C::NTRK3 (n = 1), TPR::NTRK1 (n = 1), TPM3::NTRK1 (n = 1), MYH10::NTRK1 (n = 1). One (12.5%) patient received entrectinib as first-line therapy, other patients (7/8, 87.5%) received entrectinib as secondor subsequent-line therapy. Three (37.5%) patients had undergone surgery before treatment with entrectinib: 2 had R2 resection, 1 had R","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"68 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136345463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The results of therapy with venetoclax, daratumumab and plerixafor as part of the conditioning regimen in chemotherapy-refractory acute leukemia in children","authors":"M. A. Klimentova, L. N. Shelikhova, M. A. Ilushina, S. L. Blagov, M. E. Perminova, А. M. Popov, S. A. Kashpor, M. S. Fadeeva, Yu. V. Olshanskaya, S. Yu. Glushkova, D. E. Pershin, D. N. Balashov, А. А. Maschan, M. A. Maschan","doi":"10.24287/1726-1708-2023-22-3-14-27","DOIUrl":"https://doi.org/10.24287/1726-1708-2023-22-3-14-27","url":null,"abstract":"The main outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) in chemotherapy-refractory acute leukemia remain suboptimal due to a high relapse rate. The incorporation of targeted anti-leukemia agents into the conditioning regimens is a potential approach to improve the efficacy of HSCT. We assessed the safety and potential efficacy of the addition of venetoclax, daratumumab, and plerixafor to the conditioning regimens in children with chemotherapy-refractory acute leukemias who received allogeneic TCRab/CD19-depleted HSCT. We used data from a pilot study, as well as the data of patients from a retrospective cohort who received similar therapy according to the individual indications. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. All 43 patients (33 acute myeloid leukemias (AML), 8 T-cell acute lymphoblastic leukemias (T-ALL) and 2 acute leukemias of ambiguous lineage) had active disease status at the time of transplantation. The preparative regimen included myeloablative conditioning based on either total body irradiation or treosulfan or melphalan. A haploidentical related donor was used as a graft source in 38 cases, while a fully matched related or unrelated donor was used in 5 cases. The engraftment was observed in 93% of cases, no excessive toxicity was noted. MRD-negative complete remission was achieved in 37 patients (86%). The cumulative incidence of grade II–IV acute graft-versus-host disease (GvHD) was 10%, and the cumulative incidence of chronic GvHD was 5%. At 2 years, transplant-related mortality was 7%, relapse incidence was 52%, event-free survival was 41%, and overall survival was 51%. The overall survival rate for the AML group was 58% and 25% for the T-ALL group. Our data show that the addition of targeted agents to the conditioning regimens is safe, however, does not significantly improve the results of HSCT in the study cohort of patients.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"76 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136345458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk factors for coagulation inhibitor development in children with severe hemophilia A","authors":"E. V. Dmitriev, A. V. Liubushkin","doi":"10.24287/1726-1708-2023-22-3-58-64","DOIUrl":"https://doi.org/10.24287/1726-1708-2023-22-3-58-64","url":null,"abstract":"Aim of the study: to examine the role of potential risk factors in inhibitor development in previously untreated patients (PUPs) (or minimally treated patients) with severe hemophilia A. The study was approved by the Independent Ethics Committee and the Scientific Council of the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology (the Republic of Belarus). The study included 89 boys who underwent regular follow-up for severe hemophilia A at the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology (the Republic of Belarus) from 1998 to 2022. The median age (10th–90th percentile) at diagnosis of hemophilia was 8.0 (1.0–21.0) months, the baseline factor VIII activity was 0.7% (0.4–0.95%). Age at first exposure to factor VIII concentrate was 11.0 (1.0–31.0) months. Out of 89 patients, 23 children had severe hemophilia A with inhibitors. The cumulative incidence of inhibitors in the whole group of PUPs was 31.0 ± 5.6%. The cumulative incidence of hemophilia A with inhibitors was higher in the patients with null mutations (37.0 ± 6.9%) than in the patients with non-null mutations (6.5 ± 6.0%) (the log-rank test, p = 0.041). The use of plasma-derived FVIII concentrate (approved for use in neonates and for prophylaxis) from one manufacturer was associated (c2 = 8.53; p = 0.004) with a lower incidence of factor VIII inhibitors (up to 21.3 ± 8.5%) compared with the incidence in the group of patients treated with FVIII concentrates from different manufacturers (45.2 ± 7.8%). Age (> 1 year old or < 1 year old) at first exposure to FVIII had no effect on the formation of inhibitors (the log-rank test, p = 0.746). Such factors as age at diagnosis of hemophilia (odds ratio (OR) 0.99; 95% confidence interval (CI) 0.93–1.024; p = 0.991) and baseline factor VIII activity (OR 0.99; 95% CI 0.8–1.06; p = 0.09) were not associated with inhibitor development. The first measurements of activated partial thromboplastin time (APTT) ratio (patient APTT value over the APTT reference value) (OR 1.89; 95% CI 0.72–5.09; p = 0.21) and FVIII recovery in vivo (OR 0.74; 95% CI 0.27–2.01; p = 0.55) were not associated with inhibitor development either. We have confirmed that one of the main risk factors for FVIII inhibitor development is F8 gene mutations. The incidence of inhibitors among the patients who received plasma-derived FVIII concentrates (recommended for use in PUPs in the neonatal period) from one manufacturer was lower than among those who received FVIII from different manufacturers.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136345461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-dependent changes in platelet function of a patient with &lt;i&gt;SLFN14&lt;/i&gt;-related macrothrombocytopenia","authors":"E. Yu. Rashevskaya, D. M. Polokhov, D. V. Fyodorova, A. A. Ignatova, E. A. Ponomarenko, E. V. Raykina, I. V. Mersiyanova, A. V. Poletayev, E. V. Trukhina, S. A. Plyasunova, P. А. Zharkov, M. A. Panteleev","doi":"10.24287/1726-1708-2023-22-3-156-165","DOIUrl":"https://doi.org/10.24287/1726-1708-2023-22-3-156-165","url":null,"abstract":"Platelet-type bleeding disorder-20 is a rare inherited thrombocytopenia caused by mutations in the SLFN14 gene. We report a case of a female patient with SLFN14 mutation, macrothrombocytopenia, severe hemorrhagic syndrome and a positive family history who was followed up from the age of 17 to 19. The 3-year follow-up showed a tendency towards partial normalization of platelet counts (from 47 to 82 × 109/L) and morphology. Platelet size and granularity as well as the density of glycoprotein (GP) membrane receptors such as GP Ib/V/IX and GP IIb/IIIa decreased. GP IIb/IIIa activation was impaired and there were no positive changes over time. The dense granules indicators were stably elevated. The parameters of a-granules (assessed by P-selectin expression) did not differ from the control group. The proportion of procoagulant phosphatidylserine-positive platelets at rest was increased and the potential to form procoagulant platelets upon activation was reduced. As the patient grew older, her bleeding disorder symptoms abated and she showed a tendency towards normalization of platelet laboratory parameters. All investigations were performed after obtaining informed consent from the patient and her parents in accordance with the Declaration of Helsinki.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"100 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136345946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The use of next generation sequencing technologies for the diagnosis of inborn errors of immunity","authors":"E. A. Polyakova, I. E. Guryanova, V. R. Vertelko, A. V. Liubushkin, K. Ya. Skapavets, S. N Aleshkevich, Yu. S. Zharankova, S. O. Sharapova, M. V. Belevtsev","doi":"10.24287/1726-1708-2023-22-3-177-184","DOIUrl":"https://doi.org/10.24287/1726-1708-2023-22-3-177-184","url":null,"abstract":"Primary immunodeficiencies are congenital genetically determined immune disorders. Recent advances in molecular genetic technologies have enabled a simultaneous analysis of a large number of genes in a patient. The purpose of this study was to analyze the mutational spectrum in DNA samples collected from patients with various types of primary immunodeficiencies. In this study, we applied next-generation sequencing technology using a panel developed at the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology and consisting of 290 genes that are associated with primary immunodeficiencies according to the existing literature. The testing was carried out in 96 patients with a clinical history suggesting a primary immunological defect. As a result, 37.5% of cases (36/96 patients) were found to harbor genetic defects that lead to disorders of the immune system.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"46 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136345450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A successful second allogeneic hematopoietic stem cell transplantation from an alternative donor in a patient with loss of HLA heterozygosity relapse of juvenile myelomonocytic leukemia: case series analysis","authors":"L. A. Tsvetkova, A. A. Osipova, A. V. Evdokimov, P. V. Kozhokar, Zh. Z. Rakhmanova, I. M. Barkhatov, O. V. Paina, O. S. Epifanovskaya, E. V. Babenko, N. E. Ivanova, D. V. Kozlov, T. L. Gindina, T. А. Bykova, E. V. Semenova, L. S. Zubarovskaya","doi":"10.24287/1726-1708-2023-22-3-28-35","DOIUrl":"https://doi.org/10.24287/1726-1708-2023-22-3-28-35","url":null,"abstract":"Juvenile myelomonocytic leukemia (JMML) is a rare and aggressive myeloproliferative/myelodysplastic neoplasm of early childhood characterized by activation of the Ras signaling pathway. Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only proven curative treatment for JMML. However, the 5-year overall survival is about 52–64%. In this work, we analyzed 4 clinical cases of patients with relapses of JMML with loss of heterozygosity in HLA (LoH) after allo-HSCT. The patients' parents gave their consent to the use of their children's data, including photographs, for research purposes and in publications. Two patients received a second allo-HSCT from an alternative donor, two patients – from the same donor. A positive result in the form of a durable remission was observed in one patient who underwent a second allo-HSCT from an alternative donor and restored HLA genetic heterozygosity. At the same time, immunotherapy with infusions of donor lymphocytes led to the development of graft-versus-host disease without potentiating the antileukemic effect. Thus, a second allo-HSCT from an alternative donor for the treatment of relapsed JMML with HLA LoH is necessary to restore the “graft-versus-JMML” response. The study was approved by the Independent Ethics Committee and the Scientific Council of the I.P. Pavlov First Saint Petersburg State Medical University of Ministry of Healthcare of the Russian Federation.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135040057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of interferon-gamma level on the health status of patients with sickle cell disease in Basrah","authors":"W. N. Ibraheim, H. A. Jasim, A. S. Abdullah","doi":"10.24287/1726-1708-2023-22-3-65-67","DOIUrl":"https://doi.org/10.24287/1726-1708-2023-22-3-65-67","url":null,"abstract":"Sickle cell disease (SCD) is one of the most prevalent autosomal recessive diseases, characterized by the generation of abnormal hemoglobin S. Our study aimed to assess how the serum level of interferon-gamma affects the health status of patients with SCD in Basrah. A total of 90 participants were enrolled in this study and divided into two main groups: a SCD group and a control group. The SCD group included 30 patients with SCD in steady state and 30 patients with SCD in vasoocclusive crisis; the control group included 30 ageand sexmatched apparently healthy individuals. Approval was obtained from the Research Ethics Committee of the College of Medicine, University of Basrah before conducting the study. Two milliliters of venous blood were drawn from all the participants, and ELISA tests were utilized to determine the levels of serum interferon-gamma. There was a statistically significant increase in the serum level of interferon-gamma among SCD patients (both in steady state and in crisis) compared to the control group (p = 0.05). There were no significant differences in the levels of interferon-gamma between the patients in steady state and during vaso-occlusive crisis (p &gt; 0.05). Interferon-gamma may influence the general health of sickle cell patients and contribute to the cause of inflammation, no matter whether the patient is in stable condition or is experiencing a crisis.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"97 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136345456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reticulocyte hemoglobin content as a marker of iron deficiency in premature newborns with very low birth weight. A simple tool for diagnosing iron deficiency","authors":"D. R. Sharafutdinova, E. N. Balashova, Yu. V. Kessler, Yu. V. Sukhova, A. R. Kirtbaya, А. Yu. Ryndin, T. Yu. Ivanets, O. V. Ionov","doi":"10.24287/1726-1708-2023-22-3-146-155","DOIUrl":"https://doi.org/10.24287/1726-1708-2023-22-3-146-155","url":null,"abstract":"Reticulocyte hemoglobin content (RET-He) is a promising marker of iron deficiency (ID) in newborns. Objective: to determine the diagnostic value of RET-He as a marker of ID in premature newborns with very low birth weight (VLBW). We conducted a single-center retrospective cohort study, which included 66 premature infants admitted to the National Medical Research Center for Obstetrics, Gynecology and Perinatology named the Academician V.I. Kulakov of the Ministry of Healthcare of the Russian Federation. Data were obtained from January 2016 to December 2018. The gestational age ranged from 29 to 32 weeks. Laboratory examination included blood tests on the 1 st and 3 rd day of life, then every 10–14 days until the day of life, then every 10–14 days the Institute of Neonatology and Pediatrics; discharge from hospital, and the measurements of serum iron, ferritin, transferrin on the 7 th until the discharge from hospital. This clinical study was approved by the Biomedical Research Ethics Committee (Minutes No.12 of 17 November 2016) and the Scientific Council (Minutes No.19 of 29 November 2016) of the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after the Academician V.I. Kulakov of Ministry of Healthcare of the Russian Federation. RET-He was the highest at birth and declined gradually thereafter in premature newborns reaching the lowest values after 3 weeks of life (median (interquartile range) 28.4 (25.8–34.8) pg (on the 1st day of life – 40.0 (35.7–41.9) pg and 33.5 (29.2–36.6) pg at the time of discharge). A low RET-He level was associated with low reticulocytes, with no changes in hemoglobin. There was a positive correlation between RET-He and MCH. D-He decreased from 1 to 42 days of life as a marker of increasing anemia. There was a negative correlation between RET-He and Hypo-He (p < 0.005). Starting from 42 days of life, or by the time of discharge, 32% of premature infants (n = 21) had a low ferritin level and 77% (n = 51) of premature infants had a low RET-He level, of which 21 infants developed ID (a positive correlation between RET-He and ferritin after 42 days of life (r = 0.34, p = 0.046)). There was no correlation between RET-He and ferritin in newborns without ID. Also, there were no correlations between RET-He and iron and RET-He and transferrin. After 42 days of life, RET-He less than 28.4 pg was a marker of ID (sensitivity 83.3% and specificity 93.7%). Low RET-He, D-He, RBC-Hе and high microR, Hypo-He were the earliest markers of ID in premature infants which predicted a decrease in serum iron and ferritin levels. RET-He, D-Не and Hypo-He are biomarkers with accurate diagnostic value of ID in premature infants with VLBW.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"27 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136345940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular genetic diagnosis in the group of hemophilia A patients in Belarus: 12 new allelic variants in the &lt;i&gt;F8&lt;/i&gt; gene","authors":"A. V. Liubushkin, I. E. Guryanova, E. V. Dmitriev, V. R. Vertelko, E. A. Polyakova, L. I. Volkova, O. V. Aleinikova","doi":"10.24287/1726-1708-2023-22-3-48-57","DOIUrl":"https://doi.org/10.24287/1726-1708-2023-22-3-48-57","url":null,"abstract":"Hemophilia A is the most common severe bleeding disorder caused by various genetic changes in the F8 gene, leading to coagulation factor VIII deficiency. Hemophilia A is characterized by high heterogeneity of genetic defects. The severity of hemophilia A varies depending on the type of genetic defects in the F8 gene. More than 3000 unique variants of the F8 gene are associated with the hemophilia A. Approximately 30% of genetic defects occur de novo. The aim of this study is to determine the spectrum of genetic defects in the F8 gene in children with hemophilia A in Belarus. The study was approved by the Independent Ethics Committee and the Scientific Council of the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology (the Republic of Belarus). The study included 98 patients with hemophilia A, who had been treated or followed up at the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology (the Republic of Belarus). Patients were categorized into 3 groups based on the severity of their disease: severe (n = 82), moderate (n = 3), and mild (n = 13). Twenty (20.4%) patients had a history of inhibitors to factor VIII. For our study, we used venous blood samples. Genomic DNA was isolated from leukocyte suspension (obtained from the whole blood samples) using phenol-chloroform extraction. All severe hemophilia A patients were prescreened for intron 22 and 1 inversions in the F8 gene using inverse and multiplex polymerase chain reaction assays, respectively. Sequencing of F8 coding regions was carried out by next generation sequencing. All clinically relevant variants were confirmed by Sanger sequencing. Genetic testing revealed that 99% of the patients with hemophilia A (n = 97) had pathogenic variants in the F8 gene. Intron 22 and intron 1 inversion mutations within the F8 gene were detected in 45.1% (n = 37) and 1.2% (n = 1) patients with severe hemophilia A, respectively. Two patients had an abnormal pattern of intron 1 inversion, not previously described in the literature. A total of 48 different variants in the F8 gene were detected in 57 patients using next generation sequencing. Eleven of the 48 genetic variants identified have not been previously reported.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"38 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136248337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}