Publications by authors named "Elena Raykina"

5 Publications

  • Page 1 of 1

Unique Combination of Diamond-Blackfan Anemia and Lynch Syndrome in Adult Female: A Case Report.

Front Oncol 2021 16;11:652696. Epub 2021 Apr 16.

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

We present an extremely rare clinical case of a 38-year-old Russian patient with multiple malignant neoplasms of the uterus and colon caused by genetically confirmed two hereditary diseases: Diamond-Blackfan anemia and Lynch syndrome. Molecular genetic research carried out by various methods (NGS, Sanger sequencing, aCGH, and MLPA) revealed a pathogenic nonsense variant in the gene: NM_000179.2: c.742C>T, p.(Arg248Ter), as well as a new deletion of the chromosome 15's locus with the capture of 82,662,932-84,816,747 bp interval, including the complete sequence of the gene. The lack of expediency of studying microsatellite instability in endometrial tumors using standard mononucleotide markers NR21, NR24, NR27, BAT25, BAT26 was demonstrated. The estimated prevalence of patients with combination of Diamond-Blackfan anemia and Lynch syndrome in the world is one per 480 million people.
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http://dx.doi.org/10.3389/fonc.2021.652696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085342PMC
April 2021

Relative expansion of CD19-negative very-early normal B-cell precursors in children with acute lymphoblastic leukaemia after CD19 targeting by blinatumomab and CAR-T cell therapy: implications for flow cytometric detection of minimal residual disease.

Br J Haematol 2021 May 14;193(3):602-612. Epub 2021 Mar 14.

National Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation.

CD19-directed treatment in B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) frequently leads to the downmodulation of targeted antigens. As multicolour flow cytometry (MFC) application for minimal/measurable residual disease (MRD) assessment in BCP-ALL is based on B-cell compartment study, CD19 loss could hamper MFC-MRD monitoring after blinatumomab or chimeric antigen receptor T-cell (CAR-T) therapy. The use of other antigens (CD22, CD10, CD79a, etc.) as B-lineage gating markers allows the identification of CD19-negative leukaemia, but it could also lead to misidentification of normal very-early CD19-negative BCPs as tumour blasts. In the current study, we summarized the results of the investigation of CD19-negative normal BCPs in 106 children with BCP-ALL who underwent CD19 targeting (blinatumomab, n = 64; CAR-T, n = 25; or both, n = 17). It was found that normal CD19-negative BCPs could be found in bone marrow after CD19-directed treatment more frequently than in healthy donors and children with BCP-ALL during chemotherapy or after stem cell transplantation. Analysis of the antigen expression profile revealed that normal CD19-negative BCPs could be mixed up with residual leukaemic blasts, even in bioinformatic analyses of MFC data. The results of our study should help to investigate MFC-MRD more accurately in patients who have undergone CD19-targeted therapy, even in cases with normal CD19-negative BCP expansion.
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http://dx.doi.org/10.1111/bjh.17382DOI Listing
May 2021

Chimerism evaluation in measurable residual disease-suspected cells isolated by flow cell sorting as a reliable tool for measurable residual disease verification in acute leukemia patients after allogeneic hematopoietic stem cell transplantation.

Cytometry B Clin Cytom 2020 Dec 28. Epub 2020 Dec 28.

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

Background: The presence of minimal/measurable residual disease (MRD) before or after hematopoietic stem cell transplantation (HSCT) is known as a predictor of poor outcome in patients with acute myeloid (AML) or lymphoblastic (ALL) leukemia. When performed with multiparameter flow cytometry (MFC), assessment of residual leukemic cells after HSCT may be limited by therapy-induced shifts in the immunophenotype (e.g., loss of surface molecules used for therapeutic targeting). However, in such cases, questionable cells can be isolated and tested for hematopoietic chimerism to clarify their origin.

Methods: Questionable cell populations were detected during the MFC-based MRD monitoring of 52 follow-up bone marrow samples from 37 patients diagnosed with T cell neoplasms (n =14), B cell precursor ALL (n = 16), AML (n = 7). These cells (suspected leukemic or normal) were isolated by flow cell sorting and tested for hematopoietic chimerism by RTQ-PCR.

Results: The origin of cells was successfully identified in 96.15% of cases (n = 50), which helped to validate the results of MFC-based MRD monitoring.

Conclusions: We believe that a combination of MFC, cell sorting, and chimerism testing may help confirm or disprove MRD presence in complicated cases after HSCT.
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http://dx.doi.org/10.1002/cyto.b.21982DOI Listing
December 2020

The Clinical and Genetic Spectrum of 82 Patients With Deficiency Including a c.256_257delAA Founder Variant in Slavic Countries.

Front Immunol 2020 10;11:900. Epub 2020 Jun 10.

Laboratory of Molecular Biology, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.

Variants in recombination-activating genes () are common genetic causes of autosomal recessive forms of combined immunodeficiencies (CID) ranging from severe combined immunodeficiency (SCID), Omenn syndrome (OS), leaky SCID, and CID with granulomas and/or autoimmunity (CID-G/AI), and even milder presentation with antibody deficiency. We aim to estimate the incidence, clinical presentation, genetic variability, and treatment outcome with geographic distribution of patients with the defects in populations inhabiting South, West, and East Slavic countries. Demographic, clinical, and laboratory data were collected from -deficient patients of Slavic origin via chart review, retrospectively. Recombinase activity was determined by flow cytometry-based assay. Based on the clinical and immunologic phenotype, our cohort of 82 patients from 68 families represented a wide spectrum of deficiencies, including SCID ( = 20), OS ( = 37), and LS/CID ( = 25) phenotypes. Sixty-seven (81.7%) patients carried and 15 patients (18.3%) carried biallelic variants. We estimate that the minimal annual incidence of deficiency in Slavic countries varies between 1 in 180,000 and 1 in 300,000 live births, and it may vary secondary to health care disparities in these regions. In our cohort, 70% ( = 47) of patients with variants carried p.K86Vfs33 (c.256_257delAA) allele, either in homozygous ( = 18, 27%) or in compound heterozygous ( = 29, 43%) form. The majority (77%) of patients with homozygous p.K86Vfs33 variant originated from Vistula watershed area in Central and Eastern Poland, and compound heterozygote cases were distributed among all Slavic countries except Bulgaria. Clinical and immunological presentation of homozygous p.K86Vfs33 cases was highly diverse (SCID, OS, and AS/CID) suggestive of strong influence of additional genetic and/or epigenetic factors in shaping the final phenotype. We propose that p.K86Vfs33 is a founder variant originating from the Vistula watershed region in Poland, which may explain a high proportion of homozygous cases from Central and Eastern Poland and the presence of the variant in all Slavs. Our studies in this cohort of founder variants confirm that clinical and immunological phenotypes only partially depend on the underlying genetic defect. As access to HSCT is improving among RAG-deficient patients in Eastern Europe, we anticipate improvements in survival.
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http://dx.doi.org/10.3389/fimmu.2020.00900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325958PMC
May 2021

Risk Factors for and the Clinical Impact of Cytomegalovirus and Epstein-Barr Virus Infections in Pediatric Recipients of TCR-α/β- and CD19-Depleted Grafts.

Biol Blood Marrow Transplant 2017 Mar 27;23(3):483-490. Epub 2016 Dec 27.

Department of Hematopoietic Stem Cell Transplantation, Dmitriy Rogachev Federal Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia. Electronic address:

Alpha/beta T cell and CD19 depletion are used to improve the outcomes of hematopoietic stem cell transplantation (HSCT). We evaluated the burden of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in pediatric patients after this HSCT type. A cohort of 182 patients with malignant (n = 114) or nonmalignant (n = 68) disorders was transplanted from either matched unrelated (n = 124) or haploidentical (n = 58) donors. The cumulative incidence of CMV and EBV viremia were 51% and 33%, respectively. Acute graft-versus-host disease (GVHD) grades II to IV, D-/R+ serology, and malignant HSCT indications were associated with increased risk of CMV viremia. CMV disease developed in 10 patients (6%). The occurrence of CMV viremia was not associated with inferior outcomes. Acute GVHD grade ≥ II was the only factor significantly associated with an increased risk of EBV viremia. Rituximab significantly decreased the rate of EBV reactivation in a subgroup that received a higher B cell dose in the graft. The rate of EBV-associated disease was .5%, and EBV viremia did not affect survival. TCR-α/β and CD19 depletion are associated with a significant rate of CMV viremia that does not affect survival. The hazard of EBV post-transplant lymphoproliferative disease (PTLD) is eliminated by the combination of CD19 depletion and rituximab.
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http://dx.doi.org/10.1016/j.bbmt.2016.12.635DOI Listing
March 2017