Nijmegen breakage syndrome (NBS) and ataxia-telangiectasia (AT; Louis–Bar syndrome) are primary immunodeficiencies (PID) associated with chromosome instability and DNA repair defects that predispose individuals to an increased risk of various malignancies. In our study, we retrospectively analyzed clinical characteristics and outcomes of 28 cancer cases in 14 patients with AT and 10 patients with NBS who had been treated at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology between January 2007 and December 2022. 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. The most common type of malignancy was mature B-cell non-Hodgkin lymphoma (B-NHL) (42%), with diffuse large B-cell lymphoma (DLBCL) accounting for 91% of all B-NHL cases. Other cases included T-cell acute lymphoblastic leukemia (ALL) (n = 3), B-cell ALL (n = 2), Hodgkin lymphoma (n = 3), NK/T-cell lymphoma (n = 1), T-cell lymphoblastic lymphoma (n = 1), peripheral T- cell lymphoma (n = 2), medulloblastoma (n = 1) epithelioid rhabdomyosarcoma (n = 1), T-cell prolymphocytic leukemia (n = 2). A total of 4 patients were diagnosed with second malignancies (2 children with AT and 2 children with NBS. The diagnosis of PID was suspected or confirmed before the initiation of cancer therapy in 62% of AT patients and in 100% of NBS patients. Treatment was given in accordance with standard protocols with chemotherapy dose modifications. A total of 93% of patients with AT and 80% of patients with NBS required dose reduction. The level of response was quite high: 81% of patients with AT and 58% of patients with NBS achieved complete remission. According to our data, the use of reduced-dose chemotherapy regimens helps to achieve an acceptable toxicity profile without reducing the overall effectiveness of treatment.
For citation: S.V. Voronin, R.A. Zinchenko, I.Yu. Efimova, S.I. Kutsev, A.V. Marakhonov, A.A. Mukhina, G.A. Novichkova, D.E. Pershin, Yu.A. Rodina, A.G. Rumyantsev, A.Yu. Shcherbina. Neonatal screening, postnatal diagnosis and tactics of preclinical treatment and prevention of primary immunodeficiencies in children. Guidelines by the experts from the National Association of Experts in Primary Immunodeficiencies (NAEPID) and the Association of Medical Genetics (AMG) of Russia. Pediatria n.a. G.N. Speransky. 2023; 102 (2): 11-33. DOI: 10.24110/0031-403X-2023-102-2-11-33.
Hereditary angioedema (HAE) due to C1-inhibitor (C1-INH) deficiency (HAE-C1-INH) is a rare (orphan) autosomal-dominant disease related to primary immunodeficiencies with a defect in the complement system and is characterized by recurrent, unpredictable edema attacks involving various organs and tissues. The recurrent episodes of edema are not amenable to the usual therapy methods and often are life-threatening conditions, especially in pediatric patients. The most pressing issue for the attending physician is the choice of the drug from the available range, taking into consideration its mechanism of action, route of administration and other parameters. This Article summarizes the properties of drugs currently available for the HAE attacks relief in pediatric patients in Russia, including the results of clinical trials, and the Authors’ own experience in the use of Icatibant and a human C1-esterase inhibitor as drugs of choice for the edema relief in the pediatric patient cohort. The purpose of this retrospective study was to evaluate the equivalence and safety of Icatibant and a C1-inhibitor concentrate for the edema management. Materials and methods used: the study included 34 HAE-C1-INH patients who had experienced 302 attack episodes in total. The inclusion criteria were a registered episode of angioedema in a patient aged 0 up to 18 y/o, confirmed HAE diagnosis and one of the two studying drugs intake within 24 hours after the onset of the first edema symptoms. Patients were administered with Icatibant, subcutaneously, or with C1-esterase inhibitor, intravenously. The efficacy was evaluated by comparing the presence of relief and/or relief of symptoms during the mentioned therapy. All of the adverse reactions during the therapy were also recorded in order to assess the drugs’ safety. Results: a total of 302 attack episodes were analyzed in 34 patients in the period from 2016 to 2021. Icatibant was used in 225 (74.5%) cases in 34 patients, and human C1-esterase inhibitor was used in 77 (25.5%) cases in 27 patients. It was allowed to use both drugs in the same patient in different angioedema episodes. The age of the children included in the analysis at the time of the first episode ranged from 1 to 14 y/o (Me 4.5 y/o). The edema was peripheral in most of the studied cases. The drugs were found to be equivalent in terms of duration until the edema symptoms’ relief (Me duration was 30 min. in both drugs, p=0.005), but not in terms of duration until the symptoms cut-off, - with greater values for Icatibant compared to the C1-inhibitor human esterase (p=0.394). Conclusion: a relatively similar efficacy and safety of both drugs as well as the possibility for their use in all age groups were recorded. It is therefore necessary to take into consideration the availability of the satisfactory venous access when choosing a drug for stopping the edema; the patient’s age (in order to ensure the fastest possible administration of the drug counting from the onset of edema); the remoteness of a patient’s location during the attack from the nearest available and satisfying medical facility; the patient’s and/or his/her parent(s)/caretaker(s) preferences. The study demonstrated that both Icatibant and the C1-inhibitor concentrate have high safety profile.
Первичные иммунодефицитные состояния (ПИДС)-редкие, генетически детерминированные нарушения иммунной системы. Чаще всего ПИДС проявляются инфекционными и аутоиммунными заболеваниями, но по мере увеличения продолжительности жизни больных с ПИД на фоне успешной терапии более значимым стал повышенный риск развития злокачественных новообразований (ЗН), прежде всего лимфом. Так, частота развития ЗН у пациентов с ПИДС составляет от 4 до 60%. В патогенезе развития лимфом при ПИДС важна роль онковирусов, однако имеют место и неинфекционные причины. Лимфомы при тяжелой комбинированной иммунной недостаточности (ТКИН) встречаются крайне редко и, как правило, представлены посттрансплантационными лимфопролиферативнми заболеваниями. Развитие истинных лимфом при ТКИН-крайне редкое событие. Мы приводим описание двух клинических случаев лимфом у детей с ТКИН с успешно проведенной непротокольной терапией лимфомы и последующей трансплантацией гематопоэтических клеток. Родители дали согласие на использование информации о ребенке в статье. ключевые слова: дети, тяжелая комбинированная иммунная недостаточность, лимфома, трансплантация гематопоэтических стволовых клеток
CTLA4 deficiency is a primary immunodeficiency state (PIDS) caused by monoallelic mutations in the gene of the same name, and belongs to the group of immunodeficiencies with immune dysregulation. This work analyzes the results of 11 patients with CTLA4 mutations observed at the Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology from October 2012 to January 2021. In 10 of 11 patients had some manifestations of immune dysregulation, the most frequent were cytopenias (10/11), lymphoproliferation (9/11) and lung damage caused by the type of interstitial lymphocytic lungs disease (9/11). Almost all patients had such abnormal immune parameters as hypogammaglobulinemia or dysgammaglobulinemia, lymphopenia. Currently, there is no standardized treatment for these patients, however, targeted therapy with biologically modified CTLA4 is a promising approach to the treatment of autoimmune complications in patients with CTLA4 deficiency. The only curative treatment option for patients with PIDS is hematopoietic stem cell transplantation, but in order to make conclusions about the effectiveness and safety of this treatment, a long period of observation and large groups of patients are required.
The aim of this study was to analyze the clinical and laboratory data of 101 patients (61 boys, 40 girls) diagnosed with PFAPA syndrome. The age of onset of PFAPA syndrome ranged from 8 to 36 months (the median age of onset was 18 months). 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 of Ministry of Healthcare of the Russian Federation. In most cases, clinical manifestations included recurrent fevers, acute tonsillitis (in 84% of cases, the tonsils were covered with a whitish coating), and cervical lymphadenitis. More rarely, the patients had diarrhea, vomiting, myalgia, arthralgia, and rash. All of the patients met the criteria proposed by G.S. Marshall. Our management strategies for patients with PFAPA syndrome include symptomatic treatment with antipyretics, short-term glucocorticosteroid therapy, and tonsillectomy. The majority of patients have complete resolution of PFAPA symptoms by the age of 7 regardless of the type of therapy.
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