Трансплантация аллогенного костного мозга (ТКМ) до сих пор остается единственным методом, который может вылечить больных хроническим миелолейкозом (ХМЛ). Это доказано наблюдением за пациентами, которые после ТКМ уже десятки лет находятся в полной молекулярной ремиссии без какой-либо поддерживающей терапии. Представленный в статье 20-летний опыт выполнения ТКМ от HLA-идентичных сиблингов больным ХМЛ свидетельствует о возможности биологического выздоровления 70—80% больных в 1-й хронической фазе ХМЛ. Впервые обсуждаются вопросы, касающиеся современных взглядов на место ТКМ в терапии больных ХМЛ в эпоху широкого применения ингибиторов тирозинкиназ.
Sera of thirty patients with acute and chronic immune neutropenias for different target cells: polymorphonuclear leukocytes (PMNL), macrophages, T and B lymphocytes are studied. An increase of the level of antigranulocyte antibodies is associated with a decrease of PMNL count, whereas a decrease of these antibodies' level is paralleled by an increase of the neutrophil count. It is noteworthy that the sera of patients with acute neutropenias contain autoantibodies similar to antibodies to CD13 antigen, which react mainly with the neutrophils. The sera of patients with chronic neutropenias contain antibodies similar to anti-CD45 antibodies and react with all target cells.
Two groups were distinguished among patients with autoimmune neutropenia with manifest antigranulocytic antibodies. One group consisted of patients whose sera reacted with all forms of leukocytes (granulocytes, monocytes, T and B lymphocytes), like CD45 monoclonal antibodies. Sera of patients from the other group reacted only with polymorphonuclear leukocytes and monocytes, similarly as CD13 monoclonal antibodies. Immunologically distinguished types of neutropenia were characterized by a typical chronic or acute clinical course.
Erythrocyte chimerism, graft versus host reaction, and course of disease were studied in patients subjected to bone marrow transplantation from 40 HLA identical sibs and 7 monozygotic twins. Disease relapses were observed in 35% of patients after allogenic and much more often in those after isogenic bone marrow transplantation. Relapses occurred in all patients subjected to transplantation from monozygotic twins. These results may be explained by the genetic and biological deficiencies of bone marrow cells from HLA identical sibs. 15% of recipients developed an acute graft versus host reaction after transplantation from HLA identical sibs; this is three times less than after transplantation from genetically unrelated donors, as reported elsewhere.
HLA levels were estimated in the plasma of allogeneic bone marrow recipients with and without graft-versus-host disease (GVHD). It was found that the level of plasma-soluble HLA is elevated in recipients with developing acute GVHD and that a rise in these antigens coincides with the onset of clinically manifest GVHD.
Apheresis was applied in 17 patients with hypoplastic anemia, myelodysplastic syndrome, chronic renal failure and other diseases sensitized to HLA. Apheresis was done for removal of anti-HLA antibodies and prevention of nonhemolytic transfusion reactions. Multiple massive apheresis led to a marked decrease in the antibody level. After the first or second apheresis with removal of 700.0-2000.0 ml of plasma weekly half of the patients showed increasing titres of lymphocytotoxic antibodies.
Investigations were conducted in 4 infants with alloimmune neutropenia caused by leuko-agglutinins (2 cases) and granulo-cytotoxins (2 cases) detected in the mothers' and infants' sera. Anti-granulocytic antibodies reacted with granulocytes of the child and father but did not react with the mother's own cells. A more severe clinical course (repeated pyo-inflammatory diseases, sepsis) was recorded in infants with alloimmune neutropenia caused by granulo-cytotoxins, alloimmune neutropenia was characterized by disorders in neutrophil phagocytic activity (mainly, due to decreased digestive capacity of cells), inhibition of colony-forming capacity of precursor-cells of granulocytopoiesis; a tendency to T-lymphocytopenia was noted during the study of cellular immunity parameters. Prognosis was favourable in all the cases of neutropenia. The maximum term of neutropenia duration was 6 months. The catamnesis has shown that the development of the infants is normal and they fall ill not often.