Vol 17, No 1 (2018)

Acute myeloid leukemia (AML) with t(8;21) or inv(16) have been considered as unique group within AML and are usually reported as core binding factor AML (CBF-AML) but there is significant clinical and biological heterogeneity within and relapse incidence reaches up to 40%. It is known that, translocations involving CBFs are not sufficient to induce fulminant leukemia alone, therefore is considered as a model for the multistep pathogenesis of AML. To characterize more broad spectrum of genetic changes we performed extensive mutational analysis of 54 genes by high-throughput sequencing in 30 patients with t(8;21)-AML. The molecular landscape of pediatric AML with t(8;21) was highly heterogeneous and harbored frequent mutations in genes activating tyrosine kinase signaling (including KIT, N/KRAS, and FLT3) – 60% in group with variable mutant allele ratios. Mutations in genes that regulate chromatin conformation or encode members of the cohesin complex were observed with high frequencies – 43% as well. These data support the theory of synergic cooperation between these events and suggest that diverse cooperating mutations may influence CBF-AML pathophysiology as well as clinical behavior and point to potential unique pathogenesis of t(8;21). The adoption of advances in DNA sequencing as a high-throughput sequencing technology is a useful tool in diagnostics of pediatric AML.

The association of aplastic anemia (AA) with other autoimmune diseases (AID) is rarely described and so far not systematically evaluated. We have analysed the literature data and present our own experience. We assessed the incidence and the outcome of concomitant AID in a retrospective, single-center study of 370 patients with AA treated between 1996 and 2014 with either immunosuppression (296) or hematopoietic stem cell transplantation (74) and a median follow-up time of 7 years (0.5–18). Results: Clinically manifest AID were observed in 10 out of 370 (2.7%) patients. Age at diagnosis of AA was similar in patients without AID compared to patients with AID (median, 10,9 versus 10 years; p > 0.05). In 3 patients where the diagnosis of AID was done before AA therapy, response to antithymocyte globulin was good for AA (2 out of 3) but not for AID (0 out of 3). In 7 patients in which AID occurred after first-line therapy, the median time to the AID was 6 months (range 2 months–13.4 years). Response to antithymocyte globulin was good for AA (7 out of 7), but treatment of AID was successful in 43% (3 out of 7) patients. Conclusions: The association of AA with AID in children is very rare. Most cases of AA in association with AID benefitted from IST, but IST was not influence to outcome of concomitant AID.

Childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) with intrachromosomal amplification of chromosome 21 (iAMP21) has very unfavorable prognosis when treated according as standard risk group, mainly due to high risk of relapce. The outcome is improoving dramatically when the patients were treated as high risk. In our study we analyzed clinical parameters and outcome in children with BCP-ALL and iAMP21 according to trial Moscow-Berlin 2008 (ALL-MB 2008). The majority of patients were stratified in standard and intermediate risk group. Seven years event free survival (EFS) in patients with iAMP21 and without iAMP21 was 0.48 ± 0.24 and 0,87 ± 0,2 respectively with cumulative incidence of relapse 0.41 ± 0.24 и 0.07 ± 0.2. BCP-ALL with iAMP21 needs some changes in current stratification strategy and new approaches to treatment. For faster and accurate detection of iAMP21 evaluation by FISH technique must be applied.

A retrospective analysis was made in 40 patients who underwent the examination and treatment in Dmitry Rogachev National Research Center from January 2014 to July 2017. Median age at the time of surgery was 7 years (range 4 m.–18 years). All patients underwent a comprehensive examination to determine the operation type. Precision neurolysis and facial nerve preservation were carried out in all cases of the absence of macroscopic invasion of the tumor into nerve. Facial nerve monitoring during parotidectomy was used in 45% (n = 18) patients. Follow-up period varied between 3 months and 3.5 years. There was no recurrences. Frequency of immediate postoperative facial nerve paresis was 27.5% (n = 11), from which only 2,5% (n = 1) was permanent paresis. Type of surgery was the only one risk factor of postoperative facial nerve dysfunction. Thus, age, reoperation, closely spaced tumor, operating time and malignant tumors were not risk factors of intraoperative facial nerve injury. Nerve-preserving surgery showed its effectiveness, allowing the functional state of the facial nerve to be preserved without incidental injury to the radical removal of the neoplasm of the parotid chewing area especially important in childhood and adolescence.

The article describes a clinical case of right atrial thrombosis in a newborn with congenital malformation (a teratoma of the sacrococcygeal region of large size). The dynamics of ultrasound study is presented against the background of anticoagulant therapy of thrombosis. Specific features of conducting a newborn with thrombotic complications are described. A new approach to the diagnosis and correction of hemostasis disorders in newborns is presented: a comprehensive evaluation of the parameters of thrombodynamics, hemostasiograms and anti-Xa activity against anticoagulant therapy. The risk factors for right atrial thrombosis in a newborn are given. The complexities encountered in the treatment of thrombosis in a newborn are analyzed.

Wiskott–Aldrich syndrome (WAS) is a Х-linked combined immunodeficiency, characterized by thrombocytopenia, eczema, infections and predisposition to autoimmunity and tumors. The severity of the disease correlates with localization of the mutations in the WAS gene. In the most cases WAS is lethal during the first years of life, except of rare patients with the milder XLT. HSCT is a curative option for the majority of patients with WAS. In some cases conservative management is possible. This article presents a family case of the milder form of Wiskott–Aldrich syndrome.14 y.o. patient's condition is described in details.

Congenital diserythropoietic anemias are a group of rare inherited diseases causing uneffective erythropoiesis and multiple morphological changes in erythroblasts. Their differential diagnosis involves a study of the morphology of minor bone marrow cell populations that requires a selective cell enrichment. Here we describe two methods of the population enrichment by erythroid cells (including the self-developed cell-binding microarray) for their subsequent study by methods of light and electron microscopy.

The assessment of thrombosis and bleeding risks is one of the most important tasks of laboratory diagnostics of disorders in the hemostasis system. For this purpose the highly specialized tests are not always appropriate, because these assays are focused on specific markers or pathologies of individual links: the level of coagulation factors, the level of D-dimers, ADP- and serotonininduced platelet activation, effects of acetyl salicylic acid on aggregation. Nowadays, integral assays are the most promising approach, simulating hemostatic process in vivo – thromboelastography, thrombodynamics, thrombin generation. These tests are designed to specify the risk of thrombosis or bleeding with co-origin, as well as screening and monitoring of drug therapy. One of the approaches in the development of integral assays are flow systems where plasma or whole blood flow is formed over the hemostatic activator, and the growth of the thrombus is recorded on the video. There are commercially available samples of such devices, and some experience of its application in clinic. However, there are no uniform standards and clinical guidelines. This review describes examples of flow chambers exploitation for diagnosis, existing problems of its usage and the opportunities that it can provide to the clinicians.

Hodgkin lymphoma has been studied more than any other type of lymphoma. The result of those studies has lead to rapid advances in the diagnosis and treatment of the disease. The vast majority of Hodgkin lymphoma patients can be cured after first line treatment. And even for those patients who relapse or become refractory, secondary therapies are often successful in providing another remission and cure the patient. The prescribed type of treatment for individual patients depends on several factors, such as time of relapse occurance, the patient’s age, overall health and previous therapies received.