The results of treatment of acute myeloid leukemias (AML) in children remain unsatisfactory. Modern therapeutic programs with hematopoietic stem cell transplantation allow us to get 5-year overall survival rate of 65 % in primary patients. For patients with relapses or refractory AML, 5-year overall survival is about 35 %.

This article presents the possibilities of chemotherapy and hematopoietic stem cell transplantation in the treatment of AML. The possibilities of epigenetic, immune, and cellular therapy are presented for pediatric AML. Special attention is paid to targeted drugs that only beginning to be used in the complex therapy of AML. 

Erdheim–Chester disease (ECD) is a rare disease with a poor prognosis. The first two cases were reported by Jakob Erdheim and William Chester in 1930. The etiology and disease incidence are unknown. One of the main components of this disorder is a chronic uncontrollable inflammation. In 2016 ECD was classified as histiocytic neoplasm by the World Health Organization and was categorized as “tumors of histiocytes and dendritic cells”. More than half of patients testing positive for the BRAF mutation. The final diagnosis is made on the basis of histological finding. There are radiological markers indicating a possible association with the disease. This is a specific, almost pathognomonic scintigraphic picture of the skeleton, “coated” aorta, “hairy” kidney patterns on computer tomography. There is a Erdheim–Chester Disease Global Alliance (ECDGA), which try to unite and provide with information about diagnostics and treatment of this rare disease both patients and doctors. Today, there are 571 registered patients and only one from Russia. We demonstrate three clinical cases of patients with newly diagnosed ECD and the role of nuclear medicine methods in assessing the prevalence of this disease.

The minimum residual disease (MRD) for hematopoietic and lymphoid systems tumors is an important component of patient examination during therapy. The MRD detection is performed to evaluate the effect of therapy and risk stratification during chemotherapy (acute leukemia) or at the end of it (peripheral B-cell lymphomas). The main laboratory methods for MRD assessing are molecular (polymerase chain reaction) and immunological (multi-parameter flow cytometry (FC)) methods. Immunological evaluation of MRD is the standard of clinical protocols for the treatment of childhood acute lymphoblastic leukemia during induction therapy. In the case of acute leukemia in adults, MRD assessment is usually performed at the end of the consolidation course. Clinically significant and practically standardized is the immunological assessment of MRD in B-cell chronic lymphocytic leukemia.

In multiple myeloma (in World Health Organization (2016) classification – plasma cell myeloma (PCM)), work is also underway to standardize protocols and unify approaches to MRD detection. With the introduction of new drugs and treatment regimens, as well as transplantation clinical outcome of patients significantly improved and MRD value is considered as a prognostic factor. To date, the use of the MRD value as a biomarker of treatment response in PCM has been approved by the US Food and Drug Administration.

With the accumulation of our knowledge regarding the MRD and to establish the clinical significance of the FC in PCM, International Multiple Myeloma Study Group (IMWG) in 2011 was added the following definition to the traditional criteria of PCM complete remission: “Immunophenotypic complete remission” – the immunophenotypically absence of aberrant clonal plasma cells in the bone marrow when analyzing at least 1 million myelocaryocytes using a multiparameter FC (4 or more parameters).

This article discusses the evolution of immunological approaches using a multi-parameter FC to detect MRD in patients with PCM in accordance with various existing protocols, features of the preanalytical stage and general rules for FC detection of MRD in PCM. 

Immune thrombocytopenia is an immunosuppressed acquired disease characterized by low platelet levels in peripheral blood and an increased risk of bleeding. This pathology deserves special attention in cases of patients who are scheduled for surgery, which undoubtedly requires careful preparation of the patient for surgery and a complete laboratory analysis, including a thromboelastogram.

This article describes the clinical case of successful surgical treatment of a patient with immune thrombocytopenia. 

Objective: to evaluate the possibilities of ultrasound elastography for differentiation of reactive and lymphomatous superficial lymph nodes (LN).

Materials and methods. The prospective study included 138 patients with enlarged superficial LN. Based on a previous histological examination, patients were divided into two groups: 1st group (n = 108) – patients with non-Hodgkin’s lymphomas and Hodgkin’s lymphoma; 2nd (n = 30) – patients with reactive (inflammatory) changes in superficial LN. All patients underwent ultrasound elastography of the enlarged LN using ARFI technology.

Results. According to the results of ultrasound elastography, the average, minimum, and maximum shear wave velocities for enlarged LN in lymphoma (1st group) were 2.616 ± 0.684; 1.980 ± 0.557 and 3.351 ± 0.987 m / s, respectively; for LN with reactive changes (2nd group) – 1.704 ± 0.223; 1.414 ± 0.209 and 2.027 ± 0.261 m / s, respectively. Thus, the average, minimum, and maximum values of shear wave velocities significantly different between the groups (p ˂0.001). The cut off values of the average shear wave velocity in the differential diagnosis of lymphoma and hyperplasia are determined at the level of 2.05 m / s, with a sensitivity of 88.5 %, specificity of 100 %, and AUC of 0.942 (p ˂0.001).

Conclusion. Ultrasound elastography demonstrated statistically significant differences in shear wave velocity in the enlarged superficial LN in lymphoma and in inflammatory processes that can be used as a preliminary non-invasive differential diagnosis of enlarged superficial LN in these conditions. 

Background. Infectious complications cause significant mortality in children with oncological diseases during chemotherapy-induced neutropenia. The absence of sensitive and specific signs and symptoms of infectious conditions as well as its microbiological identification, leads to inappropriate antibiotic exposure. The use of laboratory biomarkers (procalcitonin (PCT) and C-reactive protein (CRP)) may be helpful for differential diagnostics of inflammatory conditions and for rational antimicrobial therapy.

Objective: to assess the current value of PCT as an additional marker for differentiating inflammatory conditions in children with chemotherapy-induced neutropenia.

Materials and methods. We presented the analysis of infectious complications in pediatric patients with oncological and onco- / hematological diseases between 2017–2020 (54 patients from 2 mnths – 17 years). PCT and CRP with clinical and instrumental diagnostic data were used for differential diagnosis of fever and development of antimicrobial therapy decision rules. Literature review concerning the discussed theme from 2006–2018 was done.

Results. Eighty-five infectious episodes in 36 months were registered, among them 42 in pts with onco- / hematological diseases and 43 – with solid tumors. In the group of bacterial infectious complications mean CRP and PCT values were significantly higher than in group of nonbacterial, moreover the discriminative value was higher for PCT. We revealed the correlation between severity of infectious complications and values of markers of acute-phase reactions. In case of non-severe bacterial complications and other types of infections significant difference was revealed only for PCT mean values.

Conclusion. Specificity of PCT concentration in bacterial infections exceeds that of CRP, which confirms the hypothesis of advantages in using PCT as differential marker of inflammatory conditions in children with malignancies. 

Background. Currently, treatment of recurrent / refractory chronic lymphocytic leukemia (CLL) involves the appointment of regimens with innovative drugs, which include ibrutinib and a combination of venetoclax and rituximab. Wherein said combination provides continuing over time high frequency eradication of minimal residual disease. Thereby, this regimen can be canceled if patients do not progress after 2 years from therapy start.

The objective of the study was to assess the pharmacoeconomic aspects of therapy with venetoclax and rituximab combination in patients with recurrent / refractory CLL compared with ibrutinib monotherapy.

Materials and methods. Analysis was performed by a simulation method from a position of the health care system. In accordance with network meta-analysis results of clinical studies in the recurrent / refractory CLL treatment (MURANO for venetoclax + rituximab combination and RESONATE and HELIOS for ibrutinib), which showed the absence of statistically significant differences in progression-free and overall survival between these treatment options, the cost-minimization method was used in the analysis. In the basic version, the model time horizon is 4 years. The price of venetoclax, rituximab and ibrutinib in the calculation corresponded to that registered (for rituximab – the median of the registered prices) with the value-added tax and the weighted average wholesale allowance taking into account the population in Russia.

When analyzing the healthcare system budget impact, the time horizon of the study was 4 years. Therapy with combination of venetoclax + rituximab starting from the first year was suggested in 100 % of newly identified recurrent / refractory CLL patients. In the base case, it was estimated that 100 patients would need therapy every year.

In the basic version of analysis, the cost of therapy after progression was not taken into account. In sensitivity analysis, an option taking into account therapy cost after progression, suggesting the appointment of venetoclax in the ibrutinib group and ibrutinib in the venetoclax + rituximab group, was also evaluated. In addition, variants with disease progression were additionally evaluated in 15 % of patients per year in the venetoclax therapy group at the end of the 2-year treatment course, as well as with an increase and decrease in the disease progression rate by 15 % in both comparison groups.

As part of the sensitivity analysis, an assessment is made of a 15 % decrease and increase in Venetoclax price, a 30 % decrease in Ibrutinib price compared to registered price and the option with a 3-year study time horizon. When analyzing the budget impact, options with an increase in the number of patients annually identified and requiring treatment by 10, 20, 30 and 50 % were evaluated. Clinical and economic analysis was carried out with a discount rate of 3.5 % per year. A budget impact analysis was performed without discounting.

Results. According to the results of cost-effectiveness analysis in the basic version, a regimen including venetoclax can reduce costs by 46.3 % compared with ibrutinib (cost for 4 years per patient is 10.422 and 19.413 million rubles, respectively). Therapy with combination of venetoclax + rituximab in 100 newly identified recurrent / refractory CLL patients annually instead of ibrutinib monotherapy will result in a reduction in therapy costs by 29.0 %, or by 1.579 billion rubles for 4 years per 100 patients starting therapy annually. The sensitivity analysis demonstrated the high reliability of the results.

Conclusion. The treatment of recurrent / refractory CLL with a combination of venetoclax and rituximab is comparable in clinical efficacy with ibrutinib monotherapy and can significantly reduce the cost of the healthcare system, and therefore increase the availability of innovative therapy for this group of patients.