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.
In this chapter, the authors described the actuality of the investigations of neurocognitive dysfunctions in patients with iron deficiency. In infants, the incidence of iron deficiency is 73%; the probability of its transition to iron deficiency anemia is very high. The development of myelin at an early age reduces the production of myelin, and the formation of g-aminobutyric acid worsens the metabolism of dopamine in the striatal brain, which leads to slowing of motor function and behavioral problems in the child. Children with iron deficiency conditions are prone to developmental delays, reduced school performance, and behavioral disorders. In older adults, cognitive dysfunctions depend on complications of the vascular nature, complicated by comorbid iron deficiency. Concomitant pathology also influences iron homeostasis. The regulating mechanisms of iron deficiency, as the same cognitive deficiency, despite the age involve more than 200 proteins from iron homeostasis, appropriate cofactors: derivatives of vitamin B, copper, manganese, zinc ions, enzymes, cell growth factors, etc. All these partners could influence separately or together to the development of iron deficiency and a complication of it neurocognitive dysfunctions. The combination of iron deficiency anemia and iron deficiency with comorbid pathology often exacerbates cognitive problems and requires a weighted approach to the choice of therapeutic correction tactics.
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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