Hematopoietic Stem Cell Transplantation: Procedure, Forecast
Last reviewed: 23.04.2024
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Hematopoietic stem cell transplantation (TSCC) is a rapidly developing technology that can potentially help cure malignant diseases of the blood (leukemia, lymphoma, myeloma) and other hematologic diseases (eg, primary immunodeficiency, aplastic anemia, myelodysplasia). The transplantation of hematopoietic stem cells can be autologous or allogeneic; it is possible to use stem cells isolated from peripheral or umbilical blood. Peripheral blood as a source of HSC is more often used than bone marrow, especially in autologous transplantation of hematopoietic stem cells. Because the stem cells from the peripheral blood are isolated more easily, the number of neutrophils and platelets is restored more quickly. TSCC, derived from cord blood, is only allowed in children, since the amount of HSC is small.
For autologous transplantation of hemopoietic stem cells, there are no contraindications. Contraindications to allogeneic transplantation of hematopoietic stem cells for the recipient is the presence of severe diseases or a condition that does not allow preoperative conditioning (chemical preparations and radiotherapy aimed at complete inhibition of the hemopoiesis and immune system functions). The ideal donor is the HLA-identical sibs, the probability of which is 25% of the siblings of the recipient. GSC transplants from fully HLA-identical unrelated donors yield results that are close in effectiveness. The probability of HLA-identity of two randomly selected individuals varies in the range 1: 1 000 000-3 000 000 (depending on the ethnicity of the recipient). The solution to the problem is to create multimillion international registers of unrelated donor volunteers. In 2009, around 15 million 000 million unrelated donor volunteers were registered in the world, ready to donate to the TSCC. The use of related HLA-incompatible THSCs does not have significant advantages over those unrelated with a similar level of incompatibility. The technology of using the transplantation of hematopoietic stem cells isolated from cord blood is effectively used in pediatric oncohematology.
[The procedure for transplantation of hematopoietic stem cells
To extract bone marrow stem cells, 700-1500 ml (max. 15 ml / kg) of bone marrow from the posterior crest of the ilium of the donor is aspirated; while using local or general anesthesia. To isolate stem cells from peripheral blood, the donor is injected with recombinant growth factors (granulocyte-colony-stimulating factor or granulocyte-macrophage-colony stimulating factor) to stimulate proliferation and mobilize stem cells followed by standard phlebotomy after 4-6 days. Then, to identify and isolate stem cells, fluorescent cells are sorted.
Stem cells are injected for 1 -2 hours by means of a central venous catheter with a large diameter. When transplanting hematopoietic stem cells in case of malignant blood diseases, the recipient is prescribed immunosuppressive drugs [eg, cyclophosphamide 60 mg / (kg x day) intravenously for 2 days with total body irradiation, busulfan 1 mg / kg orally 4 times a day for 4 days and cyclophosphamide without total irradiation] to induce remission and suppression of the immune system so that there is no rejection of the graft. Such schemes are used for allogeneic transplantation of hematopoietic stem cells, even when this malignancy is not shown, to reduce the incidence of rejection and relapse; In autogenous transplantation of hematopoietic stem cells, such a scheme is not shown. A non-myeloablative immunosuppressive regimen can reduce the risk of illness and death and is useful in elderly patients, patients with concomitant diseases and susceptible to the effect of "graft versus a tumor" (eg, with multiple myeloma).
After transplantation, the recipient receives colony-stimulating factors to reduce the duration of post-transplant leukopenia, prophylactic course of drugs to protect against infections and, for allogeneic transplantation of hematopoietic stem cells, a preventative course of immunosuppressants lasting up to 6 months (usually methotrexate and cyclosporin) to prevent a reaction from donor T lymphocytes in relation to MHC molecules of the recipient (Graft vs. Host disease, graft vs host disease - GVHD). If the patient does not fever, the use of broad-spectrum antibiotics is usually abstained. Graft survival usually occurs 10 to 20 days after hematopoietic stem cell transplantation (previously in the case of stem cell transplantation from peripheral blood) and is determined by the absolute number of neutrophils greater than 500 x 10 6 / L.
Serious early (<100 days) complications include impaired engraftment, rejection and acute GVHD. Impaired engraftment and rejection occur in less than 5% of patients and are manifested by persistent pancytopenia or an irreversible decrease in the number of blood cells. Treatment is carried out by glucocorticoids for several weeks.
Acute GVHD is noted in recipients for allogeneic transplantation of hematopoietic stem cells, in 40% of patients who received cells from Incompatible siblings, and in 80% from unrelated donors. In this condition, fever, rash, hepatitis with hyperbilirubinemia, vomiting, diarrhea, abdominal pain (with possible development of intestinal obstruction) and weight loss are noted. Risk factors include HLA- and sexual incompatibility; unrelated donor; the elderly age of the recipient, donor, or both; previous sensitization of the donor; inadequate prevention of GVHD. The diagnosis is obvious when collecting an anamnesis and an objective examination; treatment consists in the appointment of methylprednisolone 2 mg / kg intravenously once a day, increasing to 10 mg / kg in the absence of improvement within 5 days.
Serious late complications include chronic GVHD and relapse of the disease. Chronic GVHD can occur independently, develop from acute GVHD, appear after resolution of acute GVHD. Chronic GVHD usually begins 4-7 months after transplantation of hematopoietic stem cells (the period can vary from 2 months to 2 years). Chronic GVHD is observed in recipients with allogeneic transplantation of hematopoietic stem cells, in 35-50% of recipients who received cells from HLA-compatible siblings, 60-70% from unrelated donors. The disease affects first of all the skin (for example, lichenoid rash, scleroderma) and mucous membranes (for example, dry keratoconjunctivitis, periodontitis, orogenital lichenoid reactions), as well as the gastrointestinal tract and liver. The main characteristic is immunodeficiency; can also develop obliterating bronchiolitis, similar to those that develop with lung transplantation. Eventually, 20 to 40% of patients die from GVHD; The mortality rate is higher for more severe reactions. Treatment is not necessary for diseases of the skin and mucous membranes; In more severe conditions, treatment is similar to that for acute GVHD. Using monoclonal antibodies or mechanical separation, depletion of T lymphocytes is achieved in the allogeneic donor transplant, which reduces the incidence and severity of GVHD, but this also reduces the "graft-versus-tumor" effect, which can enhance cell proliferation, improve survival, and reduce recurrence rates. The relapse rate with allogeneic HSC is higher for this reason and because circulating tumor cells can be transplanted. Ex vivo studies tumor cells isolated before autologous transplantation.
In patients without chronic GVHD, the appointment of all immunosuppressants can be stopped 6 months after the transplantation of hematopoietic stem cells; thus, late complications in this group of patients are rare.
Prognosis of hematopoietic stem cell transplantation
The prognosis varies depending on the indications and the procedure being performed. In general, relapse of the disease occurs in 40-75% of recipients in autologous transplantation of hematopoietic stem cells and in 10-40% of recipients in allogeneic transplantation. The success rate (bone marrow without malignant cells) is 30-40% in patients with relapsing chemotherapy-sensitive lymphoma and 20-50% in patients with acute leukemia in remission; compared with the use of chemotherapy alone, hematopoietic stem cell transplantation increases survival in patients with multiple myeloma. The indicator of successful treatment is lower in patients with more advanced disease or with reactive solid cancer (for example, breast cancer, tumors from germinative cells). The recurrence rate decreases in patients with GVHD, but overall the death rate increases if the GVHD is severe. Intensive course of drugs, effective prophylaxis of BHPH, a course of treatment based on cyclosporine and quality maintenance therapy (eg, antibiotics, prevention of infection with the herpes virus and cytomegalovirus) increase the long-term survival after transplantation of hematopoietic stem cells without recurrence of the disease.