Publications by authors named "Margarita Belogurova"

6 Publications

  • Page 1 of 1

Ovarian tissue cryopreservation in prepubertal patients with oncological diseases: multidisciplinary approach and outcomes.

J Matern Fetal Neonatal Med 2021 Jul 18;34(14):2391-2398. Epub 2019 Sep 18.

Institute of Perinatology and Pediatrics, Almazov National Medical Research Centre, Saint-Petersburg, Russian Federation.

In children with cancer, the issues related to the quality of life are becoming increasingly important together with the improvement of survival rates. This creates an entirely new challenge - minimizing the toxicity of the antitumor therapy without reducing its effectiveness. One of the specific side effects of the antitumor therapy is gonadotoxicity, which negatively affects both the somatic and mental state of the survivors. Since ovarian stimulation is ineffective in prepubertal patients, ovarian tissue cryopreservation (OTC) remains the most promising option to preserve fertility. The primary goal of this publication is to emphasize the importance of the reproductive health problem in girls with oncological diseases, with a description of the current data of international literature on the prospects of OTC in order to preserve fertility. Another goal is to present a multidisciplinary strategy for the management of prepubertal age patients with the oncological disease within the framework of the Oncological Fertility Project at Almazov National Medical Research Center. Based on the data of Russian and international literature, as well as existing guidelines and recommendations on reproductive health, a single algorithm for selecting patients has been developed, considering the expected gonadal toxicity for the use of the OTC in prepubertal girls. The developed algorithm allows identifying patients of prepubertal age, requiring the use of new possibilities of reproductive technologies. In a long-term date, we are planning to evaluate the effectiveness of the orthotopic reimplantation technique of the cryopreserved ovarian tissue in restoring the reproductive function. A multidisciplinary team of specialists and the possibilities of the Federal Center facilitate implementing the Oncofertility Program in routine practice for girls and young women, receiving gonadotoxic treatment.
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http://dx.doi.org/10.1080/14767058.2019.1666364DOI Listing
July 2021

Heterogeneity of childhood acute leukemia with mature B-cell immunophenotype.

J Cancer Res Clin Oncol 2019 Nov 28;145(11):2803-2811. Epub 2019 Aug 28.

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 1 Samory Mashela St., GSP-7, Moscow, 117997, Russia.

Background: Flow cytometry (FCM) plays a crucial role in the differential diagnosis of Burkitt lymphoma/leukemia (BL) and B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The presence of surface IgM (sIgM) alone or with light chain restriction indicates a mature blast phenotype (BIV by EGIL) and is usually observed in BL. However, sIgM expression could also be detected in transitional BCP-ALL cases. These similarities in immunophenotype and ambiguous correspondence with other laboratory findings may challenge the correct BL diagnostics.

Methods: We retrospectively reviewed the available data from immunophenotypic, morphological, cytogenetic, and molecular genetic studies of 146 children (85 boys and 61 girls) with a median age of 10 years (range 0-18 years) who were diagnosed with BL and BCP-ALL. The blasts' immunophenotype was studied by multicolor FCM. The conventional cytogenetic analysis included G-banded karyotyping and fluorescence in situ hybridization (FISH).

Results: In 54 children classified as BIV-ALL according to the EGIL, it was demonstrated that sIgM in a minority of cases can be associated with various types of BCP-ALL. Analysis of the antigen expression profile of 105 patients with verified BL (n = 21) and BCP-ALL (n = 84) showed significant differences in BL and the sIgM(+) vs BCP-ALL immunophenotype. Thus, even in cases of ambiguous sIgM expression, these two diseases could be reliably discriminated by complex immunophenotyping. Moreover, 10 patients (7 boys and 3 girls) with BL leukemic cells did not express sIgM, and they were diagnosed with BL on the basis of other laboratory and clinical signs.

Conclusions: In conclusion, our study shows that BIV subtype is heterogeneous group of leukemia including not only the BL, but also BCP-ALL. In ambiguous cases, only a combination of multiple immunophenotypic, cytomorphologic, and genetic diagnostic technologies can allow the precise discrimination of BL and BCP-ALL and selection of the appropriate treatment scheme.
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http://dx.doi.org/10.1007/s00432-019-03010-1DOI Listing
November 2019

Rituximab and reduced-intensity chemotherapy in children and adolescents with mature B-cell lymphoma: interim results for 231 patients enrolled in the second Russian-Belorussian multicentre study B-NHL-2010M.

Br J Haematol 2019 08 9;186(3):477-483. Epub 2019 May 9.

Dmitri Rogachev National Research Centre for Paediatric Haematology, Oncology and Immunology, Moscow, Russian Federation.

The value of adding rituximab to chemotherapy in children with aggressive B-cell non-Hodgkin lymphoma (B-NHL) is still insufficiently studied. We enrolled 231 patients [mean age 9 years old (range 2-17); male:female ratio 3·4:1] with Burkitt (BL, 179 patients, 76·7%), diffuse large B-cell (32 patients, 14%), primary mediastinal B-cell (14 patients, 6%), and other (6 patients, 2·6%) B-cell lymphomas in a prospective study of immuno-chemotherapy. Stages were I-II in 32% and III-IV in 68% of the patients. Four doses of 375 mg/m rituximab were added to the Berlin-Frankfurt-Munster-NHL-90-like chemotherapy, with methotrexate being reduced or omitted in the first 2 induction blocks. The complete remission rate was 100% in limited-stage and 91·4% in advanced-stage patients. Five advanced-stage patients (2·2%) died in induction and 1 patient with stage 2 B-NHL died in remission; 11 patients in the high-risk group progressed on therapy (3 non-BL are alive after salvage) and 5 relapsed. Sixteen patients (9·7%) with advanced stage disease proceeded to transplant. With a median follow-up of 46 months, 98·5 ± 1% of patients with limited disease and 88·1 ± 2% (88·1% in Risk Group 3; 82·6% in Risk Group 4) in advanced stages are alive. This study confirmed that combined immunochemotherapy for B-lymphomas is highly effective in children, despite reducing the intensity of the induction blocks.
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http://dx.doi.org/10.1111/bjh.15944DOI Listing
August 2019

Metronomic therapy has low toxicity and is as effective as current standard treatment for recurrent high-risk neuroblastoma.

Pediatr Hematol Oncol 2017 Aug 17;34(5):308-319. Epub 2017 Nov 17.

c Department of Pediatric Oncology and Hematology , University of Brno , Czech Republic.

The metronomic therapy concept uses low doses of continuously applied chemotherapeutic, anti-angiogenetic, and immunomodulating drugs. Twenty patients with recurrent and 3 with refractory high-risk neuroblastoma were treated by the metronomic concept using celecoxib, cyclophosphamide, vinblastine, and etoposide for up to 24 months. The outcome was compared to 274 matched patients with a first recurrence from stage 4 neuroblastoma using the variables time from diagnosis to first recurrence, number of organs involved, and MYCN amplification. All were treated with dose-intensive conventional chemotherapy. The study patients experienced 1-3 recurrences and had 1-3 sites involved (osteomedullary, primary tumor, central nervous system, lymph nodes, liver, lungs) before the metronomic therapy started. Two patients in complete remission and three with active refractory disease following recurrence treatment were excluded from the outcome analysis. The curves for secondary event-free and overall survival demonstrated no significant differences. The toxicity was minimal except for ≥3 grade thrombocytopenia and leukopenia (all heavily pretreated). The treatment was realized in an outpatient setting. The metronomic approach is similarly effective as standard treatment in recurrent high-risk neuroblastoma, has low toxicity, and is applicable in an outpatient setting. A prospective study including propranolol as a fifth drug is underway.
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http://dx.doi.org/10.1080/08880018.2017.1373314DOI Listing
August 2017

A pharmacokinetic study of lipegfilgrastim in children with Ewing family of tumors or rhabdomyosarcoma.

Cancer Chemother Pharmacol 2017 Jan 16;79(1):155-164. Epub 2016 Dec 16.

Teva ratiopharm, Merckle GmbH, Ulm, Germany.

Purpose: Neutropenia is a common complication from chemotherapy, limiting optimal dosing and treatment. Lipegfilgrastim is a long-acting granulocyte colony-stimulating factor developed for the management of chemotherapy-induced neutropenia. The objectives of this phase 1, multinational, open-label, single-arm study were to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of a single body weight-adjusted dose of lipegfilgrastim and to evaluate the efficacy, safety, and tolerability of the drug in children with Ewing family of tumors or rhabdomyosarcoma treated with myelosuppressive chemotherapy.

Methods: Enrolled patients received lipegfilgrastim (100 µg/kg) 24 h after the last chemotherapy treatment in week 1. Patients were stratified into three age groups: 2 to <6, 6 to <12, and 12 to <18 years. Blood samples for PK analyses were obtained at baseline and at 3, 8, 24, 30, 48, 72, 96, 144, and 240 h postdose for the two oldest groups and up to 144 h in the youngest group.

Results: Twenty-one patients were enrolled and received lipegfilgrastim, seven in each age group. Lipegfilgrastim exposure levels were comparable across age groups, with concentrations maintained over a prolonged period after a single injection. Differences in PD were mainly associated with chemotherapy type. Most investigator-reported adverse events were attributed to chemotherapy and not to lipegfilgrastim. Severe adverse events were noted in 57% of patients; febrile neutropenia, leukopenia, neutropenia, and thrombocytopenia were more frequent among the oldest patients.

Conclusions: Results support the use of a body weight-adjusted dose to achieve equivalent initial peak exposure levels of lipegfilgrastim in children of various ages.
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http://dx.doi.org/10.1007/s00280-016-3216-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5225185PMC
January 2017

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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