Introduction. Despite the availability of results from several studies that evaluated the role of magnetic resonance imaging (MRI) in the diagnosis of multiple myeloma (MM), data on the value of MRI after antineoplastic treatment, in particular after autologous hematopoietic stem cell transplantation (auto-HSCT), are limited.
Objective. To study changes in bone marrow lesions using MRI in MM patients before and after auto-HSCT.
Materials and methods. Forty patients with MM (15 male and 25 female) aged 36 to 66 years (median age 56 years) were enrolled in a prospective study. MRI of the spine and pelvic bones was performed before and 100 days after auto-HSCT to track bone marrow changes after transplantation. MRI was carried out with a GE Signa Profile system without contrast enhancement. The nature of the lesions was determined, and the bone marrow infiltration lesions (≥ 5 mm) were counted.
Results. MR images showed a decrease in the number of foci after auto-HSCT in 17 (52%) patients, and a reduction in the volume of the tumors in 29 (88%) patients. In most patients, even when a complete response (CR) was achieved, MRI revealed residual tumor load in the bone marrow, which decreased after auto-HSCT (by 1.4 times in the number of detectable lesions, and by 2.4 times in the tumor volume).
Conclusion. By making it possible to evaluate the residual tumor load, whole-body bone marrow MRI can be used as an additional non-invasive method for assessing response to antitumor therapy in MM patients.

Introduction. Computed tomography (CT) is a powerful method of medical imaging that can reveal in skeletal bones foci of destruction, soft tissue masses and pathological fractures characteristic of multiple myeloma (MM). It has a number of valuable advantages over conventional plainfilm radiography, which has traditionally been used in the diagnosis of MM. The absence of a significant difference in the radiation load between a plain radiography and a low-dose CT makes the latter the method of choice for screening for presence and extent of osteolytic lesions.
Objective. To explore the potential of low-dose computed tomography in the diagnosis of MM and to describe characteristic structural changes of bones during treatment.
Materials and methods. One hundred and eighty-eight whole-body low-dose CT scans were performed in patients with newly diagnosed MM followed by monitoring of changes in the areas of interest according to the standard protocol.
Results. Osteolytic changes were observed in 91% of patients; 49.6% of patients showed soft-tissue masses spreading beyond the affected bones. Based on the followup CT scans according to the standard scanning protocol, we established radiological criteria of a positive response to antitumor therapy. The method has been included in the Russian multiple myeloma clinical guidelines.

Background. Proliferation of large granular lymphocytes (LGL) can be associated with viral infections, autoimmune disorders, chronic lymphoproliferative disorder of NK-cells (CLPD-NK), or T-cell large granular lymphocytic leukemia (T-LGL). Differential diagnosis between reactive and neoplastic LGL proliferation could be a challenge.
Objective. To evaluate the role of morphological, immunophenotypic (flow cytometry) and molecular genetic (PCR-based T-cell clonality) studies in differential diagnosis of LGL proliferation.
Materials and methods. 68 patients with increased peripheral blood LGL counts were enrolled in the study. Male/female ratio was 20/48; the median age was 53 (22—79) years. Blood smear, immunophenotyping by flow cytometry, and PCR-based T-cell clonality assays (TCRG (V γ-J γ) and TCRG (D β-J β and V β-J β)) were performed in all cases.
Results. We found that morphology, immunophenotype, relative and absolute LGL counts, or heterogenic expression of T-cell markers can not distinguish between neoplastic and reactive LGL proliferation. Clonal TCRG (V γ-J γ) and TCRG (D β-J β) gene rearrangements were observed in reactive LGL lymphocytes and T-LGL. Complete rearrangements of TCRG (V β-J β) genes were specific for malignancies and were not detected in any case of reactive lymphocytosis.

Background. Chronic myeloid leukemia (CML) is a common myeloproliferative disease characterized by pathologic activity of the fusion gene BCR/ABL, which encodes a tyrosine kinase that stimulates uncontrolled cell proliferation and DNA instability. Up to 20% of CML patients demonstrate primary resistance or non-optimal response to targeted tyrosine-kinase inhibitors (TKI) therapy.
Objective. To find new potential genetic markers of TKI resistance by whole exome sequencing.
Materials and methods. The study included eight patients with Ph+ CML in the chronic phase (CF). After 6 months of follow-up period patients were divided into two groups: four with an optimal response to TKI therapy and four with a non optimal response. The validation group included 62 patients (32 with optimal and 30 with non-optimal response to therapy). Exome sequencing was performed using the Ion Torrent PGM platform. Alignment was performed on the human genome (GRCh37). Sanger sequencing was conducted on an ABI PRISM 3500xl . Statistical processing of the results was carried out using MS Office Excel and SPSS21.
Results and conclusion. Exome sequencing revealed seven single-nucleotide variants (SNVs) associated with therapy outcomes: ANKRD35-rs11579366, DNAH9- rs1990236, MAGEC1-rs176037, TOX3-rs10653661, THSD1-rs3803264, MORN2-rs3099950, and PTCRArs9471966. Validation of these variants in 62 patients did not confirm prognostic role of any of the individual SNVs or their combinations. An additional analysis of the number of SNVs in 9000 genes revealed 75 genes with significant differences in the number of SNVs. Enrichment analysis showed that these genes are involved in cell adhesion, cell contacts, T-cell antigen activation, and inhibition of IFNα-mediated antiproliferative signaling. Many of these genes are also associated with a variety of cancers (renal, lung and breast cancer). Possible multifactorial nature of the efficacy of therapy complicates the search of new prognostic markers.

Background. There are no clinical guidelines in Russia regarding the use of central venous access devices in hemophilia despite venous access being crucial for hemophilia treatment.
Objective. To analyse different long-term vascular access options in hemophilia patients.
Materials and methods. We reviewed 12 cases (11 hemophilia patients and 1 patient with von Willebrand disease) in which long-term vascular access was established. All patients were treated in the National Research Center for Hematology between 2014 and 2018.
Results. In total, 17 long-term central venous devices (LTCVD) were implanted in 12 patients (11 peripherally inserted central catheters, PICCs, and 6 ports). The PICCs were implanted in 7 patients of whom 4 had FVIII inhibitors. Median PICC dwell time was 214 days (7 to 464 days); the incidence of catheter-associated bloodstream infections was 0.41 per 1000 PICC days. The ports were implanted in 6 patients (3 via internal jugular veins, 2 via subclavian veins, and 1 via femoral vein in a patient with stenosis and thrombosis of the superior vena cava system). The incidence of catheter-associated thrombosis in this group was 0.15 per 1000 port days, and the incidence of catheter-associated bloodstream infections was 0.15 per 1000 port days.
Conclusion. In inhibitor hemophilia patients and hemophilia patients who need intravenous therapy other than with clotting factors, PICCs are a good choice. It is necessary to estimate the demand for LTCVDs in hemophilia patients in Russia and to develop national guidelines regarding their use.

Introduction. Hemoglobin variants can be either hemoglobinopathies which are responsible for diseases or non-pathological variants which couldn’t make any detectable disorder. Carriers with structural variant haemoglobin have 30 to 50% of the variant haemoglobin in their red blood cells. The most common variant hemoglobin is hemoglobin S, which accounts for 40% of carriers and responsible for more than 80% of disorders related to hemoglobinopathies. According to the World Health Organization (WHO) there are at least 948 000 new carrier couples, and over 1.7 million pregnancies to carrier couples every year. Thus, it is very important to provide a systematic carrier screening program specially among athigh risk couples. This might help to prevent or/and reduce the incidence of blood disorders that related to variant haemoglobin. The aim of this study was to assess the variant haemoglobin among Saudis who were attending the Centre of premarital screening.
Materials and methods. A total of 9008 blood samples were studied among Saudi male and female who were attending the Centre of premarital screening from January 2015 to October 2015 at Taif City. Samples were then analyzed by High Performance Liquid Chromatography.
Results. Abnormal haemoglobin fractions on HPLC were displayed in 118 cases. The result of this study showed that Hb S heterozygous was presented as the major abnormality with 58.5% followed by beta thalassemia minor with 21%.
Conclusion. Clear understanding the genetics and the prevalence of these diseases will provide opportunities for prevention or/and reduce the incidence. Thus, this study suggests that in addition to the huge efforts already accomplished by the Saudi Ministry of Health to prevent at-risk marriages, the early diagnosis for these disorders might be offered for young adults as they can discuss the issue in the early stage of the marriage proposal.

This paper reviews the literature on occult hepatitis B virus (HBV) infection (OBI), discussing its definition, pathogenesis, diagnosis and prevention. OBI is characterized by a low level of HBV replication, when the viral DNA is detected in the liver at low concentrations (< 200 IU/ml) and may be undetectable in serum, while antibodies to the HBV core protein (anti-HBc) and/or to its surface protein (anti-HBs) may be present. In most cases, OBI is caused by the virus whose genome is replicatively competent and comparable to the genomes isolated from individuals with HBsAgpositive infection. Host factors are strongly involved in the induction and maintenance of an occult form of infection. Clinical recovery from HBV infection does not imply complete eradication of the virus, but only the ability of the immune system to keep reproduction of the remaining virus in the liver under control. Numerous clinical studies have shown that any immunosuppressive factors may trigger HBV reactivation producing a typical serological profile of active infection. The clinical significance of OBI is summarized by the following three key points: 1) the “occult” virus can be transmitted, mainly with blood transfusions or liver transplantation, followed by development of acute hepatitis B in the recipient; 2) HBV can get reactivated during immunosuppression, and 3) latent HBV infection contributes to the progression of other chronic liver diseases and plays a role in hepatocarcinogenesis. Testing for anti-HBc is a simple precautionary measure to prevent transmission of HBV during blood transfusion, especially in immunocompromised patients.
This review is based on 60 publications, 3 Russian and 57 foreign, retrieved from by the following databases: PubMed, Google Scholar, Scopus, Springer, Cochrane Library, Wiley Online Library, and Russian Science Citation Index.

In recent years, the incidence of infections caused by multidrug-resistant bacteria, particularly by extendedspectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E), has increased. One of the major issues in the treatment of infections caused by these pathogens is their resistance to many antimicrobial agents. In patients with hematological malignancies, the most common source of infection is their own intestinal flora, which gets translocated from the intestinal mucosa into the bloodstream. The article discusses the prevalence and sources of infection with ESBL-E, as well as the necessity of monitoring of gut colonization with these bacteria during chemotherapy.

This molecular genetic study of a girl with moderate hemophilia A is the first Russian report describing the cause of hemophilia in a female patient. The proband’s father suffers from severe hemophilia A and has a common F8 gene mutation, specifically an inversion of intron 22 (Inv22). Along with the Inv22 mutation inherited from her father, the girl was also found to be heterozygous for three benign mutations in the F8 gene: с.1010-27G>A, c.3780C>G (p.D1260E), and c.3864A>C (p.S1288=). A dramatically skewed X-chromosome inactivation was detected in the proband’s blood and buccal epithelium samples (95:5% and 85:15% respectively). The maternal X-chromosome was selectively inactivated. The paternal X-chromosome with the mutant F8 gene remained active, and thus caused hemophilia A in a heterozygous female.

Summary. We present a ten-year follow-up of a patient with severe congenital thrombotic thrombocytopenic purpura (TTP), who received permanent replacement therapy with freshly frozen plasma (FFP) transfusions. At presentation, the patient had no activity of plasma ADAMTS-13 and an increased concentration of von Willebrand factor multimers. During treatment, the disease was complicated by occasional acute renal failure and hepatic dysfunction. These complications developed when the intervals between plasmapheresis were extended, and were partially reversible. Given the absense of ADAMTS-13 inhibitor and the early childhood history of the signs of the disease (petechiae during infections), the patient was diagnosed with congenital TTP. After the nature of the disease was thus established, plasmapheresis was replaced with regular transfusions of FFP. The intervals between transfusions were determined by monitoring the falling platelet counts and ADAMTS-13 activity. As a result of the treatment over the past 6 years, there have been no serious complications, and the patient leads an active lifestyle, studies and works. Over the course of the treatment, the patient received over 150 transfusions of FFP (amounting to over 100 liters of FFP), but despite the numerous transfusions, the patient has not contracted viral hepatitis or HIV. Thus, a tailored replacement therapy with FFP administered to a patient with congenital TTP helped to avoid severe debilitating complications, while the use of quarantine or virus-inactivated FFP minimized the risk of transfusionrelated infections.