PurposeFavorable outcomes were achieved for children with acute lymphoblastic leukemia (ALL) with the first Russian multicenter trial Moscow–Berlin (ALL-MB) 91. One major component of this regimen included a total of 18 doses of weekly intramuscular (IM) native Escherichia coli-derived asparaginase (E. coli-ASP) at 10000 U/m2 during three consolidation courses. ASP was initially available from Latvia, but had to be purchased from abroad at substantial costs after the collapse of Soviet Union. Therefore, the subsequent trial ALL-MB 2002 aimed at limiting costs to a reasonable extent and also at reducing toxicity by lowering the dose for standard risk (SR−) patients to 5000 U/m2 without jeopardizing efficacy.MethodsBetween April 2002 and November 2006, 774 SR patients were registered in 34 centers across Russia and Belarus, 688 of whom were randomized. In arm ASP-5000 (n = 334), patients received 5000 U/m2 and in arm ASP-10000 (n = 354) 10 000 U/m2 IM.ResultsProbabilities of disease-free survival, overall survival and cumulative incidence of relapse at 10 years were comparable: 79 ± 2%, 86 ± 2% and 17.4 ± 2.1% (ASP-5000) vs. 75 ± 2% and 82 ± 2%, and 17.9 ± 2.0% (ASP-10000), while death in complete remission was significantly lower in arm ASP-5000 (2.7% vs. 6.5%; p = 0.029).ConclusionOur findings suggest that weekly 5000 U/m2E. coli-ASP IM during consolidation therapy are equally effective, more cost-efficient and less toxic than 10000 U/m2 for SR patients with childhood ALL.Electronic supplementary materialThe online version of this article (10.1007/s00432-019-02854-x) contains supplementary material, which is available to authorized users.

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This study was aimed to systematize magnetic resonance imaging (MRI) presentation of toxic leukoencephalopathy, to find the correlation between method of central nervous system (CNS) leukemia prevention and changes on MRI, to find relationship between existence leukoencephalopathy on imaging and neurocognitive deficits in pediatric patients after anti-leukemic therapy. Brain MRI data of 48 children, who underwent a therapy course according to the ALL-MB intermediate risk protocol, was evaluated. In accordance with two arms of this protocol, they received either radiation therapy, or additional intrathecal administration of chemotherapeutic agents as a prevention of CNS leukemia. Also, neurocognitive tests were performed. According to the results of the performed investigation, 10 (50%) out of 20 children, who received cranial irradiation and 18 (66.6%) out of 27 patients, who received only intrathecal therapy demonstrated abnormal brain changes (leukoencephalopathy) according to MRI data. Leukoencephalopathy was mostly presented by diffuse zones and localized predominantly in the frontal and temporal lobes. There was no correlation between method of CNS prevention and the existence of leukoencephalopathy on MRI. The analysis of our data did not show significant differences in brain damage and severity of cognitive impairment depending on the type of prevention of CNS leukemia. Moreover, in this study no statistical correlation was found between leukoencephalopathy on MRI and neurocognitive impairment according to clinical tests data. Further long-term prospective studies and examinations should be performed to assess late neurotoxic effects.

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Background: The late treatment outcomes of pediatric brain tumors and of hematopoietic and lymphoid tissue tumors are an important focus of both rehabilitation and research. Neurocognitive and motor disorders induce further learning problems impeding social-emotional adaptation throughout a whole lifespan. Core deficits in short-term and working memory, visuospatial constructional ability, verbal fluency, and fine motor skills underlie distorted intellectual and academic achievement. This study aimed to assess the individual differences in cognitive ability and fine motor skills of pediatric tumor survivors and the age-matched healthy controls. Methods: A total of 504 tumor survivors after treatment and 646 age-matched healthy controls underwent neurocognitive and fine motor assessments. Findings: The group of tumor survivors scored significantly worse in both neurocognitive and fine motor skill in compared with the healthy control group. The pediatric brain tumor survivors (PBT group) performed worse in cognitive (p < 0.001 for verbal fluency and p < 0.001 for visuospatial constructional ability) and motor tests (p < 0.001) compared to the healthy controls. Hematopoietic and Lymphoid Tissues tumors survivors (THL group) performed worse in verbal fluency (p < 0.01) and visuospatial constructional test (p < 0.001) compared to the control group. Furthermore, the PBT group had worse results in visuospatial constructional ability (p < 0.05) and fine motor (p < 0.001) ability than the THL group. Significant differences between females and males were found in fine motor test performance in the PBT group (p < 0.05), as well as in verbal fluency (p < 0.01) and visuospatial constructional ability (p < 0.01) in the control group. Neurocognitive and fine motor skill characteristics in the THL group did not correlate with age.

Aim. To study serum concentrations of trace and macro elements and their correlations in children and adolescents after antitumor therapy, depending on the presence or absence of caries.Materials and methods. The study included 98 patients aged 4 to 17 years who were in remission after an antitumor therapy performed for acute leukemia or lymphomas. Patients with carious tooth lesions were included in group 1 (n = 34) and without caries – in group 2 (n = 64). We used inductively coupled plasma mass spectrometry to calculate the content of essential, conditionally essential and toxic elements in blood serum. The median and interquartile range were calculated, the Mann-Whitney U-test was applied to compare groups, and the Kendall rank correlation coefficient (τ) was calculated for tandem elements.Results. In both groups, the concentrations of the studied elements were within the reference ranges. In group 1, compared with group 2, higher concentrations of potassium, arsenic, iodine and boron and lower concentrations of lithium and tungsten (p < 0.05) were noted. There were no differences in the concentration of phosphorus, calcium, magnesium, manganese, gold, silver, platinum, aluminum, beryllium, bismuth, cadmium, cobalt, chromium, copper, iron, mercury, lithium, molybdenum, nickel, rubidium, antimony, tin, vanadium, zinc, zirconium and thallium between the groups. Significant correlation coefficients in both groups were obtained for the iron/manganese tandem (τ = 0.24, p < 0.05). Different values of τ were got for nickel/ manganese, cobalt/iron, manganese/phosphorus, beryllium/lithium tandems: τ = 0.342 and τ = 0.14; τ = 0.363 and τ = 0.033; τ = –0.111 and τ = –0.326; τ = –0.365 and τ = 0.42, respectively, for groups 1 and 2.Conclusion. In patients in remission after antitumor therapy, an association of caries with an increase (within reference values) in the concentration of essential (potassium, iodine) and conditionally essential elements (arsenic, boron), a decrease in the concentration of lithium and tungsten; as well as a change in the ratio of nickel/manganese, cobalt/iron, manganese/ phosphorus and change the direction of the correlation in the beryllium/lithium tandem was revealed.

Introduction.This study focuses on topical issues of etiopathogenesis, clinic and treatment of radiation injuries of hard dental tissues in patients who completed antitumor therapy.Review of literature data.In the course of reviewing both domestic and foreign sources of literature covering certain aspects of the problem, the authors formulate the principles of the differential diagnosis of radiation caries, prevention and treatment specificity.Results.The studies were performed at the TRSC “Russkoe Pole” from January 2017 to August 2018 (the median is 20 months). A group of 2005 patients who received radiation therapy for the treatment of hemoblastosis, solid tumors, including for the purpose of consolidation before the hematopoietic stem cell transplantation, was selected. The most severe lesions of the dentition were detected in 74 (3.2 %) patients during the rehabilitation period, mainly with tumors of the central nervous system: radiation caries, trisism, adentia. Radiation caries is a common complication of radiation therapy in the treatment of malignant neoplasms in children and adolescents.Conclusion.The severity of radial caries is determined by the local dose and age of the patients at the time of exposure.Conflict of interest. The authors declare no conflict of interest.Funding. The study was performed without external funding.