It has long been known that there is a link between neuron glial antigen 2 (NG2) surface expression and KMT2A gene rearrangements in acute leukemia (AL). However, the exact levels of NG2 positivity that predict the presence of KMT2A rearrangement are not known. The current study focuses on a cohort of 505 pediatric AL patients who showed any level of positive NG2 expression (greater than 1% of cells) for whom comprehensive genetic data were available. NG2 expression was measured as either the percentage of positive cells or the number of molecules on the cell surface. KMT2A gene rearrangements were identified by FISH. The fusion partner was detected with RT‐PCR, LDI‐PCR or anchored multiplex PCR followed by high‐throughput sequencing. KMT2A‐positive samples comprised a substantial proportion of the NG2‐positive cohort (180 of 505, 36%), with a total of 19 different types of translocation. Despite its occurrence in other AL genetic subgroups, NG2 expression was significantly increased in AL patients with KMT2A rearrangements in terms of both the cell percentage and number of molecules per cell. The threshold levels (TL) for NG2‐positivity were established by ROC analysis of the whole cohort and separately for children less than 1 years old and older with lymphoblastic (ALL) and myeloid (AML) leukemia. The lowest TL was defined in infants with ALL (7%), while in older children, the threshold was higher (12%). In AML patients, the situation was reversed, with 28% NG2‐positivity in infants and 14% in patients >1 year old. The defined TLs resulted in improved diagnostic performance compared to the conventional thresholds of 10% and 20% for all patient groups.
Acute lymphoblastic leukemia (ALL) with translocation t(17;19)(q21-q22;p13) TCF3::HLF (E2A::HLF) accounts for less than 1% of childhood B-lineage ALL. Since the first description, patients with this type of ALL are stratified into high-risk group. The disease often has a unique clinical presentation with disseminated intravascular coagulation and hypercalcemia, that are uncommon in other types of B-lineage ALL. This type of ALL is characterized by an extremely poor prognosis despite intensive treatment and hematopoietic stem cell transplantation (HSCT) in the first remission. In the last decade, some new data on the mechanisms of leukemogenesis in this type of ALL made it possible to come closer to understanding the reasons for the high refractoriness to chemotherapeutic agents. Along with the reports on the possible effectiveness of the BCL-2 (venetoclax) and Aurora kinase A (alisertib) inhibitors in this type of ALL, cellular immunotherapy (various chimeric antigen receptor (CAR)-T cell constructs), anti-CD19 (blinatumomab) and anti-CD22 (inotuzumab ozogamicin) monoclonal antibodies appear promising in the treatment of this disease. To date, there are neither published data on direct comparisons of the effectiveness of these methods nor specific recommended therapy protocols for these patients. It is also unclear if the new therapeutic approaches can completely replace HSCT or they only increase relapse-free survival after it. Here, we review the data on this translocation published in the medical literature and present a case report of a 3-year-old boy with this type of leukemia, who did not respond to four-component induction therapy according to the ALL-MB 2015 Protocol and received anti-CD19 CAR-T therapy with the achievement of the first MRD (minimal residual disease)-negative remission, which lasted 11 months. After MRD-relapse and unsuccessful attempt at therapy with autologous CD19/CD22 CAR-T cells, the patient developed an extended isolated bone marrow relapse. He achieved the second MRD-negative remission after reinduction therapy with inotuzumab ozogomycin and received allogeneic HSCT from a related donor. At the time of writing, the patient is in complete molecular remission for 16 months after transplantation. The patient's parents have consented to the use of de-identified clinical information and photos of the patient in scientific research and publications.
The purpose was to study the clinical and epidemiological features of respiratory syncytial virus infection in hospitalized children the first year of life with lower respiratory tract diseases in different regions of the Russian Federation (Russia) during the 2015–2016 epidemic season.Materials and methods: in the original study data of a multicentre observational study conducted on the basis of children’s hospitals in St. Petersburg, Arkhangelsk, Kazan, and Saratov are presented. Etiology of acute respiratory viral infections were confirmed by examination of smears from the posterior pharyngeal wall by polymerase chain reaction. The study sample included 991 child’s first year of life with lesions of the lower respiratory tract.Results. In the etiological structure of the surveyed children in the season of 2015-2016, RSVI ranged from 14% to 46,2%, an average of 33%. RSVI dominated in the Centers of St. Petersburg (38,3%), Arkhangelsk (36.2%) and Kazan (42.5 per cent).RSVI significantly more often (p<0.01) leads to the development of bronchiolitis (29.4% against 16.3% and 10.0%, with rhinovirus infection and parainfluenza, respectively. Patients with RSUI often develop pneumonia (23,5%) vs 20.6% and 20,0% with rhinovirus infection, and parainfluenza. Patients with RSVI often suffer severe forms of the disease require oxygen support (13,8%) and treatment in the departmentof intensive care (15,9%).Seasonal peaks of hospitalization due to RSVI in all Centres were recorded in December-April 2015 and 2016. Regional differences in monthly intensity of hospitalization of children with RSVI were established.Thus, the high prevalence of RSVI among children in the first year of life, especially with heavy and complicated forms of lower respiratory tract disorders requiring intensive care benefits, represents a socially important issue, which requires monitoring for effective prevention in children at risk.
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