Dubej L. Peculiarities of development of secondary immune deficient and it’s diagnostic in childhood acute lymphoblastic leukemia.

Українська версія

Thesis for the degree of Doctor of Science (DSc)

State registration number

0509U000244

Applicant for

Specialization

  • 14.01.10 - Педіатрія

27-02-2009

Specialized Academic Board

Д 64.600.04

Essay

Object of the study: acute lymphoblastic leukaemia (ALL) in children. Purpose of the study: to specify the mechanisms of the development of secondary immunodeficiency and create a modern system for its diagnosing in ALL children on the basis of the study of clinical-immunological peculiarities in the course of the disease. Methods of the investigation: general clinical, clinical-genealogical, haematological, cytological, cytochemical, immunological (immunochemical, immunochemiluminescent, immunophenotypical), statistical. Theoretical and practical results: when suspecting congenital developmental defects in children, ill with ALL, it is expedient to pay attention to revealing a rare pathology, Nijmegen-Breakage syndrome, caused by a congenital defect in the immune system, susceptibility to oncological diseases, ALL in particular, and mutation of 657de15. A complex of immunological markers is suggested for monitoring the course of ALL in children; it contributes to an opportune use of the sufficient scope of the accompanying defence therapy and the strategic solution of the subsequent medical tactics for disease recurrences. When making ALL diagnosis in children, it is suggested to use a broad monoclonal cntibody panel in order to impart the maximum characteristic of the antigenic structure of blast cells, since changes in the main indices of the immune system depend upon the immunophenotypical subvariant of this haemoblastosis. Such an approach will make it possible to use the accompanying therapy more individually, thereby decreasing undesirable breaks during cytostatic treatment and increasing efficacy of the therapy Novelty: for the first time, on a sufficient clinical material a complex assessment of the immune system was made; it directly broadens new notions about mechanisms in the development of the secondary immunodeficiency and a modern system of its diagnosing in children, ill with ALL. It was revealed that the regeneration of T helpers-inducers in young ALL children passed by the thymus-dependent way, whereas adolescents aged 11-14 demonstrated the prevalence of thymus-independent mechanisms in the restoration of these cells. T suppressor-cytotoxic lymphocytes regenerated faster owing to their CD8+CD28-subpopulation. They did not need any residual thymic activity and restored completely less than within three months after the end of the programmed treatment. It was found out that during the cytostatic therapy for ALL, a significant reduction was observed in the content of СD19+ lymphocytes in the peripheral blood and in the level of serum IgA, IgM, IgG, which gradually restored after the therapy was ended. A degree of disturbances in some humoral immunity indices depended upon the child’s age. The inhibition of B lymphocytes and serum immunoglobulins was longer and more profound in children aged six-ten years. In children before the age of five and adolescents at the age of 11-14, some indices of the humoral link of immunity approached the normal level faster. It was revealed that in the debut of ALL children demonstrated a high cytokine activity, which did not depend upon the immunophenotypic subvariant of this haemoblastosis. In recurrences of the diseases, irrespective of the term of its appearance, IL-6 and TNF-? concentrations rise, but IL-8 content in the blood serum falls, it being accompanied by a strong relationship of the studied cytokines with blast cells irrespective of their absolute number in the peripheral blood. This observation makes it possible to isolate IL-6, IL-8 and TNF-? as additional immunological markers of ALL course in children. Degree of introduction: results of the researches were introduced into the work of the consultation polyclinic of the Institute of Blood Pathology and Transfusion Medicine of the Academy of Medical Sciences of Ukraine (Lviv), OHMATDYT Lviv Regional Children’s Hospital and Lviv Regional Children’s Specialized Hospital, municipal Lviv City Children’s Hospital and Lviv City Hospital No. 5, as it is confirmed by acts on introduction. Sphere of application:medicine, paediatrics.

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