scholarly journals Non-spherocytic hemolytic anemia caused by erythrocyte pyruvate kinase defiiency: the analysis of genetic defects in pediatric patients, living in Russian Federation

2021 ◽  
Vol 20 (2) ◽  
pp. 84-96
Author(s):  
E. A. Cherniak ◽  
N. E. Sokolova ◽  
K. V. Semiglazova ◽  
I. N. Lavrentyeva ◽  
E. K. Donush ◽  
...  
Keyword(s):  
Medical Research ◽  
Hemolytic Anemia ◽  
Research Center ◽  
Compound Heterozygous ◽  
Missense Mutations ◽  
Pediatric Hematology ◽  
Transfusion Independence ◽  
National Medical ◽  
Retrospective Data Analysis ◽  
Minimum Age

The article presents retrospective data analysis of a cohort of patients with PKD (n = 41 patients, aged 4 months – 26,5 years, median of age – 5 years 1 month) who were examined at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology for unspecifid hereditary hemolytic anemia during the period 2013–2020. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. In all patients, the diagnosis was confimed by Next Generation sequencing (NGS). The homozygous mutations in the PKLR gene were found in 10 patients (24.39%), compound heterozygous mutations in 31 patients (75.61%), 77.78% of them were missense mutations. Gender distribution (male:female) was 1:1.73. At least once transfusion of erythrocyte suspension was required to 40 (97.56%) patients. The minimum age at the time of the debut of transfusion dependence was the fist day of life, the maximum was 4 years. Exchange blood transfusion was performed in 13 children, severe normocytic hyperregenerative anemia with transfusion of red blood cells in the fist days of life was noted in 12 children, at the 1st month of life – in 9 children, at the 2nd month of life – in 8 children, at the 3rd month – in 6 children, at the 5th month – in 2 children, at the 1st year – in 1 child, and 2 children underwent single transfusions on the background of infectious episodes at 3 and 4 years respectively. Splenectomy due to high transfusion dependence was performed in 10 patients: transfusion independence was achieved in 5 patients, in 5 – an increase in the interval between blood transfusions. Median of surgical intervention (9 patients): 7 years 4 months, minimum age – 1 year 4 months, maximum – 14 years 4 months. In total, 36 genotypes were described in 41 patients, among them were: c.1529G>A in 3 patients, c.1137_1139del / c.1456C>T – in 2 patients, c.1079G>A/c.1529G>A in 2 patients, c.1130T>C/c.1456C>T in 2 patients, other genotypes occurred once. Two mutations were the most frequent: c.1456C>T (16.67%) and c.1529G>A (16.67%). 19 (46,34%) of patients had previously not described mutations.

scholarly journals Pharmacokinetics of 13-cis-Retinoic acid in high-risk neuroblastoma patients

2020 ◽  
Vol 19 (4) ◽  
pp. 20-31
Author(s):  
E. A. Litvin ◽  
D. T. Utalieva ◽  
D. Yu. Kachanov ◽  
A. V. Pshonkin ◽  
M. Ya. Yadgarov ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
High Risk ◽  
Medical Research ◽  
High Performance ◽  
Plasma Concentrations ◽  
Neuroblastoma Cells ◽  
Research Center ◽  
Therapeutic Drug ◽  
Pediatric Hematology ◽  
National Medical

13-cis-Retinoic acid is a differentiation agent for neuroblastoma cells and is a part of post-consolidation therapy for high-risk patients. The effectiveness of this therapeutic approach is currently under study. 26 patients with high-risk neuroblastoma treated at Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology were included in the study of 13-cis-Retinoic acid pharmacokinetics by high-performance liquid chromatography assay with ultraviolet detector depending on the method of administration of drug (swallowed capsules or opened capsules before administration). This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The current study showed that the therapeutic concentration of > 2 μM when taking 13-cis-Retinoic acid at a dose of 160 mg/m2/day was achieved in two groups, regardless of the method of drug administration. However, plasma concentrations of 13-cis-Retinoic acid at 4 hours after administration on the 14th day of therapy were higher in the group of patients who swallowed the capsules (4.1 ± 1.8 μM), compared to those who could not do it (1.9 ± 1.5 μM) (p = 0.022). The introduction into the clinical practice of therapeutic drug monitoring of 13-cis-retinoic acid in high-risk neuroblastoma patients with an assessment of peak concentration and dose adjustment of the following courses may be an important point in the attempt to optimize postconsolidation therapy and improve prognosis.

scholarly journals Therapy intensification in high-risk neuroblastoma patients with poor response to standard induction: experience of Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, Immunology

2019 ◽  
Vol 18 (4) ◽  
pp. 19-28
Author(s):  
T. V. Shamanskaya ◽  
D. Y. Kachanov ◽  
A. V. Dumacheva ◽  
M. V. Teleshova ◽  
D. V. Shevtcov ◽  
...  
Keyword(s):  
High Risk ◽  
Medical Research ◽  
Induction Therapy ◽  
Poor Response ◽  
Research Center ◽  
Long Term Results ◽  
Type I ◽  
Pediatric Hematology ◽  
National Medical

High-risk neuroblastoma (NB) is characterized by unsatisfactory treatment results and low probability of long-term survival despite the multimodal therapeutic approach (chemotherapy, surgical treatment, radiation therapy, autologous hematopoietic stem cell transplantation, etc.). One of the prognostic factors in this cohort of patients is the response to induction therapy. The article presents the experience of the intensification of induction therapy in 12 patients with high-risk NB with a poor response (mixed response, stable disease) to standard induction therapy who received treatment at Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, assessing its impact on the prognosis of the disease. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Patients received an additional two courses of chemotherapy with the inclusion of a type I topoisomerase inhibitor topotecan (TCE – topotecan, cyclophosphamide, etoposide). This regimen of intensification of therapy has demonstrated its feasibility. The main grade 3–4 toxicity was hematologic. An improvement in response was achieved in 5/12 (41.6%) patients. However, long-term results of therapy remained unsatisfactory. The 3-year EFS was 16.7% (95% CI 0.0–37.8), the 3-year OS was 50.0% (95% CI 21.7–78.3). Thus, the intensification of therapy in patients with high-risk NB with a poor response to standard induction therapy did not improve treatment outcomes.

scholarly journals Neuroblastoma with localization in the neck. Own experience Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology

2019 ◽  
Vol 5 (4) ◽  
pp. 21-30
Author(s):  
D. V. Shevtsov ◽  
T. V. Shamanskaya ◽  
D. Yu. Kachanov ◽  
N. S. Grachev ◽  
K. I. Kirgizov ◽  
...  
Keyword(s):  
Medical Research ◽  
Conflict Of Interest ◽  
Risk Group ◽  
Risk Groups ◽  
High Risk Group ◽  
Research Center ◽  
Observation Group ◽  
Pediatric Hematology ◽  
Favorable Prognosis ◽  
National Medical

Introduction.Neuroblastoma (NB) is the most common extracranial solid tumor in children. As a rule, NB is localized in the adrenal gland, retroperitoneal space and posterior mediastinum. The head and neck area belongs to the rare localization of NB, which accounts for 2.6 % of cases, and is most common in children aged 0–3 years. Localization of NB in the neck in most cases has a favorable prognosis.Materials and methods.For the period from September 2013 to September 2017 (48 months) in the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology received treatment for 8 patients with NB in the neck. Examination, assessment of the prevalence of the process and stratification into risk groups in all patients were carried out according to the recommendations of the protocol of the German group for the treatment of NB NB-2004. For the purpose of histological verification of the diagnosis and detection of unfavorable molecular genetic markers, patients underwent surgical intervention, performed risk-adapted therapy according to the NB-2004 protocol.Results.The median age of diagnosis was 8.7 (1.2–34.1) months. In our cohort of patients in 87.5 % of cases, the diagnosis was made in the first year of life. In most cases, there was not only the identification of tumor masses, but also other symptoms of the disease. In 3 (37.5 %) patients the 2nd stage was established, in 1 (12.5 %) patient – the 3rd stage, in 3 (37.5 %) patients – the 4th stage and in 1 (12.5 %) patient – 4S stage of the disease. When stratifying patients into risk groups, in the observation group and the high-risk group was stratified by 3 (37.5 %) children and 2 (25 %) patients were classified as high-risk group. 3 (37.5 %) patients showed unfavorable cytogenetic abnormalities. When evaluating the response to therapy in most patients, a complete and very good partial response was stated. Overall (OS) and event-free (EFS) survival rates were 75 ± 15 % and 50 ± 17 %, respectively. The median of observation is 43 (26–61) months.Discussion.NB with the localization of the primary tumor in the head and neck area is a favorable form in terms of the stage of the disease and the risk group, however, it should be noted that in our patient cohort half of the subjects showed the development of certain adverse events, which was also reflected in the OS and EFS. Moreover, this localization dictates its risks from the point of view of the surgical stage of treatment. The main danger is complications after surgical treatment associated with the anatomical proximity of the central arteriovenous trunks, cranial nerves, and their involvement in the tumor process. In the case of the development of life threatening conditions (LTC), it is possible to use low-intensity chemotherapy courses.Conclusion.Experience Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology shows the need for timely diagnosis and the start of treatment of NB with localization in the neck. The choice of management tactics in favor of carrying out only surgical treatment is possible in patients of the observation group without the development of LTC. Not always the localization of NB in the neck region correlates with a favorable prognosis.Conflict of interest. The authors declare no conflict of interest.Funding. The study was performed without external funding.

scholarly journals Bilateral adrenal neuroblastoma: clinical presentation, diagnostic and therapeutic approaches, treatment results

2020 ◽  
Vol 19 (4) ◽  
pp. 66-81
Author(s):  
N. A. Andreeva ◽  
D. Yu. Kachanov ◽  
E. Yu. Ilyina ◽  
A. P. Shcherbakov ◽  
G. V. Tereshchenko ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Medical Research ◽  
Adrenal Insufficiency ◽  
Clinical Presentation ◽  
Survival Rates ◽  
Research Center ◽  
Mibg Scintigraphy ◽  
Treatment Results ◽  
Pediatric Hematology ◽  
National Medical

Bilateral adrenal neuroblastoma (BANB) is a very rare entity. It is more common in young children and has certain clinical features. Patients with BANB have a more favorable prognosis than patients with unilateral adrenal neuroblastoma (NB). The article presents an analysis of 29 cases of BANB in children who underwent treatment at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. The analysis was performed for the period from April 2012 to December 2018. Bilateral adrenal involvement was diagnosed on the basis of analysis/assessment of the results of all relevant imaging and instrumental tests. Additionally, we performed a retrospective analysis of the findings of computed tomography, magnetic resonance imagining, and scintigraphy with 123I-metaiodobenzylguanidine (123I-MIBG). In view of 123I-MIBG scintigraphy sensitivity threshold, and in order to confirm the diagnosis, imaging findings were reviewed by an experienced radiologist. The patients received therapy in accordance with the risk-adapted NB-2004 protocol. Here, we analyzed the details of clinical presentation of the disease, age at the time of diagnosis, time from the disease onset to diagnosis, the presence or absence of life-threatening symptoms (LTS) and adrenal insufficiency, the aspects of patient management (including special aspects of surgical treatment), and treatment results. The median age at the time of diagnosis was 1.9 months. The patients were divided into 3 groups: children with localized BANB; children with true stage 4 disease; children with stage 4S disease. Most patients had metastatic NB, whereby stage 4S cases prevailed (55%, n = 16). Given the low sensitivity of MIBG scintigraphy for the detection of small tumours (less than 2 cm), one should use a comprehensive approach to the assessment of the results of imaging and instrumental tests in patients with BANB in order to confirm bilateral involvement. At diagnosis, about half of the patients with BANB (48%) had clinical symptoms associated with the presence of a retroperitoneal tumour mass and massive hepatomegaly because of liver metastases. Thirty-four percent of patients developed LTS. One of the typical features of BANB was the frequent development of adrenal insufficiency (in 41% of cases) caused by bilateral adrenal involvement, and this should be taken into account when performing diagnostic investigations and providing treatment to patients. Since bilateral radical resection is associated with the inevitable development of adrenal insufficiency, surgical treatment should be determined on an individual basis. Bilateral adrenalectomy is not generally recommended and can be undertaken after an interdisciplinary discussion in case of unfavourable course of the disease (e.g. in case of recurrence). Even if patients with BANB develop certain complications or events (progression) their prognosis is still good. The three- and five-year event-free survival rates in patients with BANB were 86 ± 6.4%. The three- and five-year overall survival rates were 100%. The analysis of patients with BANB showed that they have a more favourable course of the disease, and this may serve as grounds for assigning such patients into a special group. In view of the degree of tumour extension, the specifics of staging, and frequent development of adrenal insufficiency, standard check-ups should be complemented by endocrine monitoring, and surgical approaches should be chosen on an individual basis.

scholarly journals Thrombopoietin receptor agonists for the treatment of severe persistent and chronic immune trombocytopenia in children: clinical data of Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, Immunology

2021 ◽  
Vol 20 (3) ◽  
pp. 12-25
Author(s):  
E. V. Suntsova ◽  
A. A. Maschan ◽  
O. N. Mironenko ◽  
D. D. Baydildina ◽  
I. I. Kalinina ◽  
...  
Keyword(s):  
Medical Research ◽  
Research Center ◽  
Platelet Response ◽  
Thrombopoietin Receptor Agonists ◽  
Receptor Agonists ◽  
Pediatric Hematology ◽  
National Medical ◽  
Thrombopoietin Receptor ◽  
Life Threatening ◽  
Transient Elevation

Thrombopoietin receptor agonists (TPO-RA) – romiplostim and eltrombopag – changed considerably the therapeutic options for severe persistent and chronic immune thrombocytopenia (ITP). The article presents the results of a retrospective study of TPO-RA efficacy and safety in patients under 18 years of age. The study was approved by the Independent Ethics Committee and Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Sixty-eight children had a total of 89 courses of TPO-RA (44 romiplostim and 45 eltrombopag). Their median age was 6.5 years. The median ITP duration was 15.8 months. All patients received previous ITP therapy (1–6 lines). Before the initiation of TPO-RA, the majority of patients had thrombocytopenia with bleeding. In most cases, the platelet response was achieved within the first 2 months of treatment. The average effective doses of romiplostim and eltrombopag were 10 mg/kg per week and 75 mg per day, respectively. Half of patients in romiplostim group and 62% of patients in eltrombopag group did not require extra therapy. The majority of patients (75.6–81.8%) achieved an overall response, but only near 50% achieved a durable (more than 24 weeks) platelet response. Six patients sustained the response after TPO-RA discontinuation. The most common adverse events (AE) of TPO-RA therapy were transient elevation in hepatic enzymes in eltrombopag group (28.9%) and thrombocytosis (18.2–22.2%) in both groups. In 6 cases the therapy was discontinued due to AEs. Two AEs were serious. Our results demonstrate that TPO-RA could safely increase platelet counts and decrease the risk of spontaneous life-threatening bleeding in nearly half of children with severe persistent and chronic ITP. TPO-RA could help to avoid long-term immunosuppressive therapy and splenectomy or delay them and the ITP remission is possible in some cases.

scholarly journals Incidence of venous thromboembolism in children with primary lymphomas

2021 ◽  
Vol 20 (3) ◽  
pp. 46-50
Author(s):  
D. A. Evstratov ◽  
L. H. Anderzhanova ◽  
A. V. Pshonkin ◽  
Yu. G. Abugova ◽  
N. V. Myakova ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Medical Research ◽  
Children And Adolescents ◽  
Median Time ◽  
Statistical Processing ◽  
Research Center ◽  
Sex Distribution ◽  
Pediatric Hematology ◽  
National Medical ◽  
Adults And Children

Cancer increases the risk of venous thromboembolism (VTE) in adults and children. The aim of our study was to evaluate the incidence of VTE in children and adolescents with lymphomas. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. A retrospective analysis based on medical data of 262 children and adolescents (0–18 years) with primary lymphomas (n = 262) who were treated in Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology since 01.01.2013 to 31.12.2019 had been performed. Such parameters as age and sex distribution of patients, the frequency, as well as the cumulative incidence of detection (CI) and differences in localization, the median time of detection of symptomatic (sVTE) and asymptomatic episodes of VT (aVTE), their relationship with central venous catheters (CVC) were analyzed. Statistical processing of the obtained data was carried out using the XLSTAT 2020 program (Addinsoft, France). The median age was 11,1 years (interquartile range (IQR) 6.5–15 years), the ratio of males to females was 2.2:1. There were 71 episodes of VTE in 65 patients (24.8%, 95% confidence interval (CI): 19.6–30). Among all episodes of VTE 31% were defined as sVTE at 400 day CI for sVTE was found to be 8.1% (95% CI: 5.4–12.2) and CI for aVTE – 18.7% (95% CI: 14.4–24.2). The median time to VTE episode was 38 days (IQR 16.5–91.5 days). There was a trend towards an earlier diagnosis of sVTE (median 23.5 days, IQR – 17–42 days) than aVTE (median 62 days, IQR 14–80 days), p = 0.075. VTE was CVC-related in 67.7 of all VTE cases. In one case, asymptomatic thrombosis of right atrium led to pulmonary embolism (PE). VTE is a frequent complication in children and adolescents with lymphomas. Most episodes of VTE were asymptomatic, one of which was the most likely cause of PE in the child. Further research is needed to find risk factors for VTE.

scholarly journals Haematological complications of X-linked lymphoproliferative syndrome type 1 and 2

2020 ◽  
Vol 19 (3) ◽  
pp. 62-72
Author(s):  
A. A. Roppelt ◽  
A. L. Laberko ◽  
V. I. Burlakov ◽  
N. Yu. Kan ◽  
Yu. A. Rodina ◽  
...  
Keyword(s):  
Medical Research ◽  
Research Center ◽  
Syndrome Type ◽  
Illumina Platform ◽  
Hematopoietic Stem ◽  
Pediatric Hematology ◽  
National Medical ◽  
Sequencing Method ◽  
Lymphoproliferative Syndrome

X-linked lymphoproliferative syndrome type 1 (XLP1) and 2 (XLP2) are primary immunodeficiencies (PID), combined in one group because of shared abnormal response to Epstein–Barr virus (EBV) and caused by mutations in SH2D1A and XIAP genes, respectively. Hemophagocytic lymphohistiocytosis (HLH) is a frequent life-threatening complication of both diseases. We analyzed haematological complications, such as HLH and cytopenia, in 12 patients with XLP1 and 11 – with XLP2. The research was approved by Independent ethic committee and the academic board of Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology (Moscow, Russia). Analyzed were patients who were treated or consulted in Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology (Moscow, Russia) since 2012 and in Russian Clinical Children's Hospital (Moscow, Russia) since 2003 to February 2020. 19 XLP1 patients from 13 families and 16 XLP2 patients from 14 families were included. For patients with haematological complications XLP diagnosis was based on the ESID criteria and genetically confirmed in 19 cases by detecting mutations in SH2D1A or XIAP gene (8 XLP1 and 11 XLP2 patients). Intracellular expression of corresponding SAP and XIAP proteins was performed by intracellular staining of SAP/XIAP in lymphocytes. Genetic analysis to detect mutations in SH2D1A and XIAP genes was performed by the Sanger sequencing method on Genetic Analyzer 3130х1 (Applied Biosystems, USA) according to the manufacturer protocol, or by the Multiplex Ligation-Dependent Probe Amplification method using SALSA MLPA Probemix P205 SH2D1A-XIAP-ITK (MRC-Holland, the Netherlands), or by the next-generation sequencing (NGS) method on NextSeq (Illumina) platform using a paired end tag (PET) sequencing method. Varying degree of cytopenia was present in 4 patients with XLP1 and 2 – with XLP2. None of XLP1 patients with cytopenia, and all XLP2 patients with cytopenia subsequently developed full HLH. Overall 8 XLP1 and 11 XLP2 patients developed HLH. HLH-associated mortality before hematopoietic stem cell transplantation (HSCT) was 75% in a group of XLP1 patients and 0% – in XLP2. HSCT was performed in 3 XLP1 patients, which was not sufficient for survival analysis and in 9 XLP2 patients, in whom overall survival was 74%. HLH is the most often haematological complication of XLP1 and XLP2. Fulminant HLH in XLP1 requires early and aggressive treatment. In XLP2 patients HLH remission can be reached on mono- or bicomponent immunosuppressive therapy which allows to reduce therapy-associated toxicity. In XLP2 patients cytopenia can precede HLH, while in XLP1 patients cytopenia is probably caused by other mechanisms. HSCT is a curative treatment for XLP1 and 2 which should be considered as soon as the diagnosis is made.

scholarly journals The development of pediatric oncology-hematology in the Russian Federation: the experience of collaboration between the National Society of Pediatric Hematologists and Oncologists and the National Medical Research Center

2019 ◽  
Vol 6 (3) ◽  
pp. 12-25 ◽  
Author(s):  
K. I. Kirgizov ◽  
S. A. Kogan ◽  
Ya. A. Erdomaeva ◽  
G. M. Muftakhova ◽  
T. G. Shlyakhtina ◽  
...  
Keyword(s):  
Medical Research ◽  
Russian Federation ◽  
Pediatric Oncology ◽  
Development Program ◽  
Research Center ◽  
Healthcare Sector ◽  
National Society ◽  
Pediatric Hematology ◽  
National Medical ◽  
The Russian Federation

The basis for constructing a vertically integrated management system in the healthcare sector in the Russian Federation is the model of functioning of national centers. One of the key components in achieving success is the interaction of the national center with a leading national society. The aim of the article is to present the experience of joint work of the National Society of Pediatric Hematologists and Oncologists (NSPHO) with the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology in the field of development of pediatric oncology-hematology in the Russian Federation. In order to accomplish the task of building a system for organizing medical care for children in pediatric oncology-hematology, a comprehensive development program was implemented, which included collecting data on the structure of the service through questionnaires in the regions, obtaining expert opinion and the subsequent creation of a service passport using data visualization. In addition, the experience of creating professional standards and the concept of a unified approach in the field of training in the specialties “Pediatric Oncology” and “Hematology” using the technology of continuing medical education are reflected. The result of the work was the formation of a single plan for the organization of the service of pediatric oncology-hematology, developed by the NSPHO in conjunction with the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology with the support of the National Medical House and under the leadership of the Ministry of Health of Russia.

scholarly journals Fisher-Evans Syndrome in Children: an Analysis of Genetic Defects and Therapy Response

2019 ◽  
Vol 18 (3) ◽  
pp. 41-45
Author(s):  
Z. A. Kuzminova ◽  
E. D. Pashanov ◽  
A. V. Pavlova ◽  
M. A. Kurnikova ◽  
I. V. Mersiyanova ◽  
...  
Keyword(s):  
Medical Research ◽  
Single Case ◽  
Disease Onset ◽  
Research Center ◽  
Evans Syndrome ◽  
Genetic Investigation ◽  
Female Ratio ◽  
Pediatric Hematology ◽  
National Medical ◽  
Male To Female

The Fisher–Evans syndrome (FES), also known as Evans syndrome (ES) is an immune hemopathy characterized by bicytopenia or pancytopenia in the absence of other diseases. FES may be either primary/idiopathic, or secondary, occurring against the background of other diseases. In children, FES is frequently related to a primary immunodeficiency disorder (PID). This article presents a retrospective data analysis of a cohort of pediatric patients (n = 14) with FES, the aim of which is to demonstrate the necessity of conducting a molecular genetic investigation for PID diagnosis. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. The patients from this cohort were presented at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, Immunology during the period 2012–2019. All of these patients underwent Next Generation Sequencing (NGS). The median age of disease onset was 5.5 years (from 5 months to 16 years). The male-to-female ratio was 1.8:1. Thanks to the results of the genetic investigation conducted on 14 patients with FES, it was possible to identify 10 children (71.4%) who had secondary FES. The median age of disease onset in patients with secondary FES was 4 years, the minimum age was 5 months, the maximum age was 12 years. The male-to-female ratio was 7:3. Most frequently, the disease onset was associated with ITP, immune thrombocytopenia (35.7% of patients) or simultaneously with ITP and AIHA, autoimmune hemolytic anemia (35.7% of patients); less frequently, the disease onset was associated with AIHA, with a subsequent occurrence of ITP (21.4% of patients). A pancytopenia was identified in 1 patient with FES associated with a PID. Among our patients with a disease onset associated with AIHA, there was not a single case with a PID. We noted an extremely low effectiveness of glucocorticoids and IVIgs for the treatment of FES: in practically 100% of cases, the patients in the analysed group required second and subsequent lines of therapy. Among other therapy types, effective for both primary and secondary FES, we should note rituximab (62% of patients stay in remission for up to 1 year) and MMF (80% of patients stay in remission for up to 1 year). On the basis of the conducted study we can conclude that male patients with FES under 18 years of age whose disease onset was associated with ITP need to be thoroughly tested for PID, including genetic testing, since patients in this group have the greatest PID incidence. Treating FES with glucocorticoids and IVIgs is nearly always not very effective and second and subsequent lines of therapy are required. The drugs of choice which are most effective for patients with FES are rituximab and MMF.

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