TRANSPLANTATION of MARROW (Latin of transplantare to replace; synonym: bone marrow transplantation, a miyelotransplantation, a medullotherapy) — introduction to the patient of marrowy cells for the purpose of temporary or stable substitution of the broken hemopoiesis.
The attempt of transplantation of marrow to the Yugoslavian physics which underwent radiation at failure of the atomic reactor was made by G. Mathe in 1958. As at transplantation of marrow considered only a blood group (on the AVO system) and a Rhesus factor (see Blood groups), it was not possible to receive long engraftment of the entered marrowy cells because engraftment of marrow requires preliminary suppression of immunity of the recipient. E. D. Thomas and sotr. in the seventies 20 century offered several ways of suppression of immunity (the so-called program of an immunosuppression) of the recipient for ensuring engraftment of histocompatible marrow and with success carried out Since m. Further O. K. Gavrilov with sotr. and other Soviet researchers confirmed a wedge, efficiency of transplantation of marrow.
Distinguish the following types of transplantation of marrow: allogenic when the recipient and the donor belong to one biol. also are similar or identical to a look on histocompatibility antigens (see Immunity transplant); autotrans
a plantation when to the patient reim-plantirut his own previously withdrawn marrowy cells; singenny Since m when the recipient and the donor have the same genetic origin within one biol. look (enzygotic, identical twins).
Indications to allogenic, sin-gene and autotransplantations of marrow can be acute leukoses and blast crisis at a myelosis (see Leukoses), a lymphosarcoma (see); allogenic and singenny Since m, besides, are shown at aplastic anemia (see. Hypoplastic anemia), a radial illness (see), agammaglobulinemias (see).
Since m carry out in specialized institutions where there is a sterile chamber (see Chamber sterile), performance of necessary serological researches and receiving from the donor of blood cells in required quantity by means of a cytapheresis is possible (see the Plasma exchange).
To donors of marrow the same requirements, as are imposed to blood donors (see the Donor). Their selection is carried out generally among brothers and sisters of patients taking into account the HLA system, the mixed culture of lymphocytes (MLC) and other compatibility tests.
Marrow for transplantation is received by repeated punctures from ileal bones (see. It is frayed a biopsy) and breasts (see. Sternal puncture) usually under the combined endotracheal anesthesia nitrous oxide with oxygen and a neyroleptanalteziya. At donors aspiration of such quantity of marrowy cells is allowed, a cut it is capable to provide necessary to lay down. effect — on average not less than 3 X 108 cells on 1 kg of the weight (weight) of a body of the recipient. Marrow for autotransplantation is taken from patients with an acute leukosis — during the first remission, from patients with a myelosis, and also lymphosarcoma (in the absence of damage of marrow) — in early terms of a disease. Such preliminary aspiration of marrowy cells for the purpose of carrying out in the subsequent autotransplantation is possible at patients at indicators of hemoglobin not lower than 10 g of % (100 g/l), quantity of leukocytes not less than 3500 in 1 mkl and the content in punctate not less than 50 000 marrowy cells in 1 mkl. The received marrowy suspension freeze for the subsequent Since m or enter to the patient immediately intravenously kapelno by means of the system for hemotransfusion (see) supplied with a dropper and the kapron filter for prevention of an embolism fatty particles and clots. In rare instances when intravenous administration of marrowy cells is impossible, change is made vnutrikostno under local anesthesia. Apply eosin test (test of Shre), and also clonal methods of cultivation of cells of a kovtny brain to definition of viability of the defrozen marrowy cells (see Cultures of cells and fabrics), etc.
Allogenic transplantation of marrow is carried out in the conditions of suppression of immunity of the recipient that provides long (from several months to several years) engraftment of the entered marrowy cells. The exception is made by patients with an agammaglobulinemia and an acute radial illness, at to-rykh immunodepressive preparation, as a rule, it is not required. For the purpose of suppression of immunity use in various combinations Cyclophosphanum (see), antilimfo-cytic immunoglobulin (see An-tilimfotsitarnaya serum), general irradiation (see), etc. At an acute leukosis (see) immunodepressive preparation, in addition to suppression of immunity, promotes the maximum destruction of tumor cells. On one of widespread schemes before allogenic Since m within 4 days intravenously enter Cyclophosphanum in a daily dose of 50 mg/kg. Transplantation is made in 36 hours after the last introduction of Cyclophosphanum. For prevention of hemorrhagic cystitis, to-ry can develop during the use of Cyclophosphanum, it is recommended to pour in days of its introduction to the patient during 24 hours
2 — 6 l of liquid (salt solutions, solutions of glucose, etc.) against the background of stimulation of a diuresis. During the use for suppression of immunity of general irradiation Since m carry out in the first 18 hours after radiation.
At use of tsitostatik, in particular Cyclophosphanum, and general irradiation engraftment of a transplant is observed in most cases. However the means and methods applied for the purpose of suppression of immunity do not provide enough elimination of leukemic cells. Thereof the recurrence of an acute leukosis which is the main reason of failures at bone marrow transplantation by the patient is possible. Rejection of an allogenic transplant at aplastic anemia against the background of the irreversible depression of a hemogenesis caused by preparation for transplantation is considered the main reason for death of patients.
The anti-lymphocytic immunoglobulin used before Since in m for suppression of immunity is entered, as a rule, against the background of reception of corticosteroid hormones. On one of schemes for the purpose of deep suppression of transplant immunity of An-tilimfotsitarny immunoglobulin is applied intravenously at the rate of 15 mg of protein on 1 kg of the weight (weight) of a body of the patient daily within
5 days; the total dose for the adult makes 4,5 — 6,0 g of protein, one-time — 0,9 — 1,2 g. In 24 hours after the last administration of drug produce Since m. At sufficient immunodepressive activity of anti-lymphocytic immunoglobulin note decrease in absolute number of lymphocytes in blood not less than by 2 — 3 times in comparison with initial. At use of anti-lymphocytic immunoglobulin engraftment of a transplant is observed approximately in 27% of cases, but only for a short span. Therefore at acute leukoses when stable replacement patol is necessary. elements of a hemogenesis, it is inexpedient to use antilimfotsi-tare immunoglobulin. It is recommended to be applied before transplantation of marrow at aplastic anemia in case of incomplete compatibility of couples the donor — the recipient.
Since the m is more effective at patients of young age (up to 40 years) in the absence of associated diseases, in particular than organic lesions of heart, kidneys, a liver. At early carrying out Since m a sick acute leukosis move away terms of emergence of resistance to chemotherapy, develop inf less often. complications, and also damages of a liver, kidneys and the hearts caused by both leukemic process, and long reception of tsitostatik.
At an acute miyeloblastny leukosis transplantation of marrow is recommended to be carried out to the period of the first remission, at an acute lymphoblastoid leukosis — during the second or third remission; at aplastic anemia it is better to carry out change not later than in
3 months after establishment of the diagnosis of a disease.
At allogenic Since m it is reasonable to immunodepressive-transgshantatsionnoy before preparation if the course of a disease allows to refrain from transfusions of components of blood since they can interfere with engraftment of marrow. If there is a need for a transfusion of eritrotsitny weight, then to the prevention of development of an isosensitization apply the svezhezagotov-lenny or defrozen erythrocytes which are repeatedly washed.
After intense immunodepressive pretransplant training the supporting hematotherapy is usually necessary (see). Before transfusion it is recommended to irradiate leukocytes and thrombocytes of in vitro, applying a dose of 1500 I am glad, sufficient for destruction of immunocompetent cells (see) at safety of other elements. Transfusions of a leykokon-tsentrat (see) and the trombotsitny weight (see) prepared from donors with similar system of histocompatibility antigens (as donors it is reasonable to attract blood relatives of the patient) are more justified. The transfusion of a leykokontsentrat is shown at decrease in quantity of leukocytes lower than 500 in 1 mkl or at inf. complications. Trombotsitny weight is entered for maintenance of number of thrombocytes within 20 000 in 1 mkl and in the presence of hemorrhages. Transfusion of a leykokontsentrat in combination with use of antibiotics can promote stopping of a bacterial infection. These actions, and also sterilization of intestines and skin, keeping of patients in sterile chambers reduce the frequency of development inf. complications.
After allogenic transplantation of marrow at certain patients fervescence, a headache, a fever, a small tortoiseshell are noted. In these cases warming, purpose of drugs of calcium, antihistaminic and drugs is shown. At engraftment of marrow the immune conflict (reaction a transplant against the owner and reaction the recipient against a transplant) which is clinically shown a so-called secondary disease can be observed (see Incompatibility immunological). It comes to light at 2/3 patients who transferred Since m against the background of preliminary immunodepressive therapy. To prevention and treatment of a secondary disease in the post-transplant period apply a methotrexate (see). At emergence of the skin defeats and an abnormal liver function caused by a secondary disease appoint antilimfotsitar-ny immunoglobulin. Such therapy not always provides stopping of displays of a secondary disease, edges serves frequent the reason of lethal outcomes. Are other cause of death of patients after transplantation inf. complications. Therefore preliminary immunodepressive training of patients, the Crimea is necessary transplantation of allogenic marrow, treatment in the post-transplant period shall be carried out in sterile conditions (see Chamber the sterile, Managed abakterial-ny environment).
At engraftment of transplantirovanny cells, usually in 2 — 3 weeks, favorable shifts in a gemogramma are observed (see): the increase in number of leukocytes and thrombocytes which is combined with subsiding or full stopping of a hemorrhagic syndrome, and at aplastic anemia is noted also increase in a hemoglobin content and quantity of erythrocytes. Studying in dynamics of punctate of marrow allows to judge extent of normalization of a marrowy hemopoiesis. Since the m, carried out after preliminary immunodepressive training of the recipient, allows to reach remission for up to 6 years at 15% of patients with acute leukoses, resistant to chemotherapy, actually being nekurabelny. Allogenic Since the m, applied during remission at acute leukoses, favorably influences their current, leads to remission at 42 — 48% of patients with the aplastic anemia proceeding in a severe form when other methods of therapy are not effective. The question of expediency repeated allogenic Since is finally not solved by m. Nek-ry researchers prefer to apply it during remission (naira., in 1 — 2 month after the first Since m). However implementation repeated Since to m is difficult because of an isosensitization of the recipient, usually arising ambassador of the first Since for m.
The miss an otransplantation of marrow is carried out at blast crisis of a myelosis, acute leukoses and a lymphosarcoma. It is applied to stopping of the expressed hypoplasia of marrow which developed as a result of massive polychemotherapy or radiation therapy. At the same time processes of a reparation of a hemopoiesis (see) do not depend on depth of his depression; normalization of a hemogenesis can be observed on 6 — the 15th days after Since by m. Engraftment of marrowy cells comes practically in all cases, the secondary disease does not arise; at inf. complications the same therapy, as well as at allogenic Since is required to m. Reimplantation of own previously prepared marrowy cells is made the patient during remission (preferably) or the beginning first recurrence of an acute miyelo-blast and second recurrence of an acute lymphoblastoid leukosis against the background of general irradiation of a sverkhintensivny-ma with doses in combination with introduction of Cyclophosphanum or other antineoplastic drugs.
Singenny transplantation of marrow differs from allogenic only in lack of need of a preliminary immunosuppression of the recipient; complications are not noted.
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