Methodological aspects of diagnostics and minimal residual disease monitoring in infant acute leukemias

Hereby we present methodological aspects and prognostic significance of minimal residual disease (MRD) monitoring in infant acute leukemias. Based on our own experience we made algorithm for detection of MRD in this group of patients. We conclude that general concordance between MRD detection by flow cytometry and real-time polymerase chain reaction (PCR) for fusion gene transcripts achieved 87.0 %. Concordance was significantly lower during induction in comparison to consolidation/intensification and relapse treatment (78.6; 90.4 and 93.4 %, correspondingly; p = 0.002). It was not dependent on presence of normal B-cell precursors. Concordance between MRD results obtained by qualitative real-time PCR in bone marrow and peripheral blood samples was 84.5 %. Interestingly, all discrepant results (22 samples 15.5 %) were MRD-positive in bone marrow, but negative in peripheral blood. Despite high qualitative concordance rate between MRD detection in bone marrow and peripheral blood samples we could not show prognostic value of MRD monitoring in peripheral blood by fusion gene transcripts. Multivariate analysis revealed that MRD-positivity at time-point 4 in bone marrow was the only significant and independent prognostic factor of unfavorable outcome in the observed group of patients (hazard ratio 7.326; 95 % confidence interval 2.378–22.565)

Modeling of complex of catalase «А» from Saccharomyces Cerevisiae with NADPH for its geometry prediction

NADPH weakly binds to Catalase «А» from Saccharomyces cerevisiae, so geometry of bound ligand is not known from X-ray crystallography. To resolve this issue com-plexes of catalase «А» from Saccharomyces cerevisiae with NADPH and it s frag-ments - inorganic momophosphates and 2 ,5 -ADP was modeled with molecular me-chanics methods. Binding site of NADPH 2 -phosphate in KATA was detected and models of 2’,5 -ADP as individual molecule and as fragment of NADPH in complexes with catalase «А» were proposed. These model data are in good agreement with known experimental results (electron density). Position of nicotinamid-ribosid is not determined.Каталаза «А» из Saccharomyces cerevisiae образует слабый комплекс с НАДФН2, поэтому его геометрия в ренгеноструктурных исследованиях не установлена. Цель настоящей работы - предсказание геометрии НАДФН2 и его фрагментов - неорганических монофосфатов и 2',5'-АДФ в связанном с ферментом состоянии методом молекулярно-механического моделирования. Результаты расчетов позволили надежно локализовать сайт связывания 2 -фосфата НАДФН2 в этой каталазе, а также предложить обоснованные модели 2',5'-АДФ в форме индивидуальной молекулы и в составе НАДФН2 в комплексе с каталазой «А», согласующиеся с известными экспериментальными данными по электронной плотности. Положение никотинамидной части НАДФН2 на основе анализа полученных моделей окончательно не установлено

Chemical-induced polyneuropathy in children with oncohematological pathology

The paper presents an analysis of clinical and instrumental studies of patients with chemo-induced peripheral neuropathyВ работе представлен анализ клинических и инструментальных исследований пациентов с химио-индуцированной полинейропатией

Aetiology of infectious complications in children with oncohematological diseases

The article presents the results of microbiological studies of different biomaterials in the diagnosis of infectious complications in children with oncohematologicaldiseases after bone marrow transplantation.Gram-negative bacteria both endogenous and possibly nosocomial origin are lead among the detected microorganisms.В статье приведены результаты микробиологических исследований различных биоматериалов, полученных при диагностике инфекционных осложнений у детей с онкогематологическими заболеваниями после трансплантации. Среди обнаруженных микроорганизмов лидируют грамотрицательные бактерии как эндогенного, так и, возможно, нозокомиального происхождения

Features of diagnostics and surgical treatment of ovarian tumors in children

The purpose of current work was to assess prognostically significant laboratory parameters in patients with ovarian tumors, as well as to determine optimal types of surgical treatment.Целью работы являлись оценка прогностически значимых лабораторных показателей, а также определение наиболее оптимальных видов хирургического лечения пациенток с опухолями яичников

The KMT2A recombinome of acute leukemias in 2023

Chromosomal rearrangements of the human KMT2A/MLL gene are associated with de novo as well as therapy-induced infant, pediatric, and adult acute leukemias. Here, we present the data obtained from 3401 acute leukemia patients that have been analyzed between 2003 and 2022. Genomic breakpoints within the KMT2A gene and the involved translocation partner genes (TPGs) and KMT2A-partial tandem duplications (PTDs) were determined. Including the published data from the literature, a total of 107 in-frame KMT2A gene fusions have been identified so far. Further 16 rearrangements were out-of-frame fusions, 18 patients had no partner gene fused to 5'-KMT2A, two patients had a 5'-KMT2A deletion, and one ETV6::RUNX1 patient had an KMT2A insertion at the breakpoint. The seven most frequent TPGs and PTDs account for more than 90% of all recombinations of the KMT2A, 37 occur recurrently and 63 were identified so far only once. This study provides a comprehensive analysis of the KMT2A recombinome in acute leukemia patients. Besides the scientific gain of information, genomic breakpoint sequences of these patients were used to monitor minimal residual disease (MRD). Thus, this work may be directly translated from the bench to the bedside of patients and meet the clinical needs to improve patient survival

Neurotoxic complications of chemotherapy in children: posterior reversible encephalopathy syndrome

The aim of the study was to present the clinical-radiological aspect of the syndrome of posterior reversible encephalopathy in children with oncological diseasesЦель публикации — представить клинико-радиологическую картину обратимой энцефалопатии у детей с онкологическими заболеваниям

The role of nelarabine in the treatment of T-cell acute lymphoblastic leukemia: literature review and own experience

Aim. The analysis of experience of nelarabine use in refractory/relapsed T-cell acute lymphoblastic leukemia (T-ALL) depending on the immunophenotype and the line of therapy. Materials and methods. All the patients with relapsed or refractory T-ALL aged from 0 to 18 years who received treatment with nelarabine as a part of the therapeutic element R6 were included in the study. For all patients a detailed immunological analysis of leukemia cells with discrimination of immunological variants TI, TII, TIII or TIV was performed. Patients administered with nelarabine as a first therapeutic element were referred to the first-line therapy group, other patients were referred to the second-line therapy group. Nelarabine was administered as intravenous infusion at a dose of 650 mg/m2, on days 1-5. Allogeneic hematopoietic stem cells transplantation (allo-HSCT) was considered for all patients. Results. From 2009 to 2017, 54 patients with refractory/relapsed T-ALL were treated with nelarabine. Five-year event-free survival (EFS) and overall survival (OS) was 28% for all patients, cumulative risk of relapse (CIR) was 27%. EFS was significantly higher in nelarabine first-line therapy group in comparison with second-line therapy group (34±8% vs 8±8%, p=0,05). In patients after allo-HSCT EFS, OS and CIR were 51±10%, 50±10% and 39,1±9,5% accordingly. The best results were achieved in patients with TI immunophenotype. No toxicity-related mortality as well as severe neurologic complications or discontinuation of therapy associated with use of nelarabine were reported. Conclusion. The use of nelarabine is an effective strategy for the treatment of relapsed and refractory T-ALL. The best treatment outcomes were obtained in patients with TI immunophenotype and in the first-line therapy group. Optimal dosage regimens can be established during controlled clinical trials

Comperetive analysis of minimal mearsurable disease monitoring by flow cytometry and real-time quantitative pcr results in infants with acute lymphoblastic leukemia

The article contains qualitative and quantitative assessment of relation of monitoring MRD results in infants with B-cell acute lymphoblastic leukemia by FCM and quantitative RT-PCR.В статье приведена оценка качественной и количественной зависимости между результатами определения МОБ методами ПЦ и ОТ-ПЦР-РВ у детей первого года жизни с острым лимфобластным лейкозом из В-линейных предшественнико