Publications by authors named "Alexander G Rumyantsev"

5 Publications

  • Page 1 of 1

TREC/KREC Levels in Young COVID-19 Patients.

Diagnostics (Basel) 2021 Aug 16;11(8). Epub 2021 Aug 16.

Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, 107031 Moscow, Russia.

COVID-19 patients with acute respiratory distress syndrome (ARDS) have an immune imbalance when systemic inflammation and dysfunction of circulating T and B cells lead to a more severe disease. Using TREC/KREC analysis, we studied the level of mature naive T and B cells in peripheral blood of COVID-19 patients and its relationship with clinical and laboratory data. TREC/KREC analysis was performed by multiplex real-time quantitative PCR on a sample of 36 patients aged 45 years or younger. The reduced TREC/KREC level was observed in ARDS patients compared with non-ARDS patients, and similar results were found for the deceased patients. During days 6 to 20 of hospitalization, a higher neutrophil-to-lymphocyte ratio (NLR) was detected in ARDS patients compared with non-ARDS patients. TREC/KREC negatively correlated with NLR; the highest correlation was recorded for TREC per 100,000 cells with the coefficient of determination R = 0.527. Thus, TREC/KREC analysis is a potential prognostic marker for assessing the severity and outcome in COVID-19.
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http://dx.doi.org/10.3390/diagnostics11081486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392044PMC
August 2021

Primary Immunodeficiencies in Russia: Data From the National Registry.

Front Immunol 2020 6;11:1491. Epub 2020 Aug 6.

Tatarstan Pediatric Republican Clinical Hospital, Kazan, Russia.

Primary immunodeficiencies (PID) are a group of rare genetic disorders with a multitude of clinical symptoms. Characterization of epidemiological and clinical data via national registries has proven to be a valuable tool of studying these diseases. The Russian PID registry was set up in 2017, by the National Association of Experts in PID (NAEPID). It is a secure, internet-based database that includes detailed clinical, laboratory, and therapeutic data on PID patients of all ages. The registry contained information on 2,728 patients (60% males, 40% females), from all Federal Districts of the Russian Federation. 1,851/2,728 (68%) were alive, 1,426/1,851 (77%) were children and 425/1,851 (23%) were adults. PID was diagnosed before the age of 18 in 2,192 patients (88%). Antibody defects (699; 26%) and syndromic PID (591; 22%) were the most common groups of PID. The minimum overall PID prevalence in the Russian population was 1.3:100,000 people; the estimated PID birth rate is 5.7 per 100,000 live births. The number of newly diagnosed patients per year increased dramatically, reaching the maximum of 331 patients in 2018. The overall mortality rate was 9.8%. Genetic testing has been performed in 1,740 patients and genetic defects were identified in 1,344 of them (77.2%). The median diagnostic delay was 2 years; this varied from 4 months to 11 years, depending on the PID category. The shortest time to diagnosis was noted in the combined PIDs-in WAS, DGS, and CGD. The longest delay was observed in AT, NBS, and in the most prevalent adult PID: HAE and CVID. Of the patients, 1,622 had symptomatic treatment information: 843 (52%) received IG treatment, mainly IVIG (96%), and 414 (25%) patients were treated with biological drugs. HSCT has been performed in 342/2,728 (16%) patients, of whom 67% are currently alive, 17% deceased, and 16% lost to follow-up. Three patients underwent gene therapy for WAS; all are currently alive. Here, we describe our first analysis of the epidemiological features of PID in Russia, allowing us to highlight the main challenges around PID diagnosis and treatment.
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http://dx.doi.org/10.3389/fimmu.2020.01491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424007PMC
May 2021

Magnetic resonance imaging of changes in the brain of children cured of acute lymphoblastic leukemia.

Hematol Rep 2019 Sep 18;11(3):7946. Epub 2019 Sep 18.

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Healthcare, Moscow.

This study was aimed to systematize magnetic resonance imaging (MRI) presentation of toxic leukoencephalopathy, to find the correlation between method of central nervous system (CNS) leukemia prevention and changes on MRI, to find relationship between existence leukoencephalopathy on imaging and neurocognitive deficits in pediatric patients after anti-leukemic therapy. Brain MRI data of 48 children, who underwent a therapy course according to the ALL-MB intermediate risk protocol, was evaluated. In accordance with two arms of this protocol, they received either radiation therapy, or additional intrathecal administration of chemotherapeutic agents as a prevention of CNS leukemia. Also, neurocognitive tests were performed. According to the results of the performed investigation, 10 (50%) out of 20 children, who received cranial irradiation and 18 (66.6%) out of 27 patients, who received only intrathecal therapy demonstrated abnormal brain changes (leukoencephalopathy) according to MRI data. Leukoencephalopathy was mostly presented by diffuse zones and localized predominantly in the frontal and temporal lobes. There was no correlation between method of CNS prevention and the existence of leukoencephalopathy on MRI. The analysis of our data did not show significant differences in brain damage and severity of cognitive impairment depending on the type of prevention of CNS leukemia. Moreover, in this study no statistical correlation was found between leukoencephalopathy on MRI and neurocognitive impairment according to clinical tests data. Further long-term prospective studies and examinations should be performed to assess late neurotoxic effects.
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http://dx.doi.org/10.4081/hr.2019.7946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761460PMC
September 2019

PPP3CB contributes to poor prognosis through activating nuclear factor of activated T-cells signaling in neuroblastoma.

Mol Carcinog 2019 03 13;58(3):426-435. Epub 2018 Dec 13.

Chiba Cancer Center Research Institute, Chiba, Japan.

We previously identified a gain-of-function mutation in PPP3CB in a neuroblastoma (NB) with MYCN amplification. Here we investigated the functional and clinical role of PPP3CB in NB. High PPP3CB expression was an independent indicator predicting poor prognosis of NB. Overexpression of wildtype or mutated PPP3CB (PPP3CBmut) promoted cell growth, but PPP3CB knockdown decreased cell growth in NB cells. Forced expressions of PPP3CB and PPP3CBmut activated NFAT2 and NFAT4 transcription factors and inhibited GSK3β activity, resulting in the increase in the expressions of c-Myc, MYCN, and β-catenin, which were downregulated in response to PPP3CB knockdown. Treatment with calcineurin inhibitor cyclosporin A (CsA) or FK506 suppressed cell proliferation and induced apoptotic cell death in both MYCN-amplified and MYCN-non-amplified NB cell lines. Expression of PPP3CB protein was decreased in response to two calcineurin inhibitors. c-Myc, MYCN, and β-catenin were downregulated at the mRNA and protein levels in CsA or FK506-treated NB cells. Our data indicate that elevated expression of PPP3CB and the expression of its constitutively active mutant contribute to the aggressive behavior of NB tumors and therefore suggest that inhibition of calcineurin activity might have therapeutic potential for high-risk NB.
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http://dx.doi.org/10.1002/mc.22939DOI Listing
March 2019

Therapy of advanced-stage mature B-cell lymphoma and leukemia in children and adolescents with rituximab and reduced intensity induction chemotherapy (B-NHL 2004M protocol): the results of a multicenter study.

J Pediatr Hematol Oncol 2014 Jul;36(5):395-401

*Federal Research Centre of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev †Russian Pediatric Clinical Hospital, Moscow ‡Municipal Clinical Hospital No. 31, Saint-Petersburg §Regional Pediatric Clinical Hospital, Yekaterinburg ∥Regional Pediatric Clinical Hospital, Nizhniy Novgorod ¶Territorial Pediatric Clinical Hospital, Perm, Russia.

Pediatric mature B-cell non-Hodgkin lymphomas (B-NHLs) are highly aggressive malignant tumors that are curable with chemotherapy (ChT). High-dose methotrexate (MTX) is considered indispensable for successful treatment, but this therapy frequently induces severe mucositis and infectious complications, especially in induction, which can cause treatment failure. A prospective multicenter trial of combined immunochemotherapy for advanced-stage B-NHL with rituximab and the modified NHL-BFM-90 protocol was conducted. The major differences from the original protocol were a decrease in the dose of MTX from 5000 to 1000 mg/m/24 h in the first 2 ChT blocks and the addition of rituximab at 375 mg/m to each of the first 4 blocks of ChT. Eighty-three newly diagnosed patients with a median age of 8.84 years with Burkitt lymphoma/leukemia and diffuse large B-cell lymphomas stage III to IV were included. Four patients died during induction ChT due to tumor lysis syndrome and infection. Two additional patients died subsequently due to tumor resistance. Complete remission was achieved in 77 (92.8%) patients; 2 patients relapsed at 1 and 3 months, and 2 developed secondary malignancies at 1 and 6.5 years, respectively, after the completion of therapy. The overall survival probability was 82%±8% with a median follow-up of 65.2 months. Combined therapy with rituximab and intensive ChT with a reduced MTX dose of 1 g/m in the 2 induction courses was feasible and produced high cure rates in patients with pediatric advanced-stage mature B-NHL.
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http://dx.doi.org/10.1097/MPH.0b013e31829d4900DOI Listing
July 2014
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