Hematopoietic Stem Cell Transplantation

The transplantation of hematopoietic stem cells (HSC) is a rapidly developing process that patients with hematological cancers (leukemia, lymphoma, myeloma) and other diseases of the blood (eg. As primary immunodeficiency, aplastic anemia, myelodysplasia) a possible cure offers. A stem cell transplant is sometimes also in solid tumors (eg. As some germ cell tumors) which react to chemotherapy.

(See also Overview transplant.) The transplantation of hematopoietic stem cells (HSC) is a rapidly developing process that patients with hematological cancers (leukemia, lymphoma, myeloma) and other diseases of the blood (eg. As primary immunodeficiency, aplastic anemia, myelodysplasia ) offers a possible cure. A stem cell transplant is sometimes also in solid tumors (eg. As some germ cell tumors) which react to chemotherapy. HSC transplantation contributes to healing in by the recovery of bone marrow following myeloablative cancer treatments replacement of abnormal bone marrow with normal bone marrow in benign hematological disorders The HSC transplantation can be performed autologous or allogenic. Stem cells can be obtained from bone marrow Peripheral blood of the umbilical cord blood, the stem cell collection from peripheral blood has replaced the bone marrow as a source of stem cells, on the whole, this v. a. with autologous HSC transplantation because the stem cell collection is easier and the number of neutrophils and platelets recover faster. The umbilical cord HSC transplantation has been limited primarily to children because there are too few stem cells in cord blood for an adult. A possible future source of stem cells are induced pluripotent stem cells (taken certain adult cells and reprogrammed to act like stem cells). Contraindications for autologous HSC transplantation do not exist, but rather for an allogeneic. Relative contraindications are patients aged> 50 years an earlier performed HSC transplantation and significant comorbidities. Allogeneic HSC transplantation is mainly limited due to lack of histocompatible donors. The ideal donor is an HLA-identical siblings. However, as is only a quarter of patients, such as sibling donor is available, is often not HLA-compatible relative or HLA-compatible foreign donors resorted (the identification is carried out by international registrations). However, the disease-free long-term survival rate may be lower than for patients with an HLA-identical sibling in these cases. For the technique of umbilical cord HSC transplantation, which is not yet well defined, the compliance of the HLA is probably insignificant. Procedure For a stem cell collection from the bone marrow to be aspirated 700-1500 ml Mark (up to 15 ml / kg) under local or general anesthetic from the posterior iliac crests of the dispenser. For the removal of stem cells from peripheral blood of the donor is treated (granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor) with recombinant growth factors to stimulate the proliferation and mobilization of stem cells, followed by a Standardaphereseverfahren 4 to 6 days later. Using a fluorescence-activated cell sorting stem cells can be identified and separated from other cells. By a large-lumen central venous catheter, the stem cells are infused into the recipient over a period of 1-2 hours. “Conditioning Regimens” Before allogeneic HSC transplantation in cancer of the recipient myeloablatives scheme as iv cyclophosphamide day first obtains a conditioning regimen (eg., 60 mg / kg / 2 days and total body irradiation or busulfan 1 mg / kg / day po 4 times daily for 4 days in combination with cyclophosphamide without total body irradiation) to induce remission and to suppress the immune system so that the transplant can be considered. Even if the indication is not cancer, similar regime are carried out in allogeneic HSC transplantation to reduce the incidence of rejection and recurrence. Such conditioning can not be used before autologous HSC transplantation in cancer; Instead, cancer-specific drugs are used. Nichtmyeloablative conditioning regime (eg. Cyclophosphamide, thymic irradiation, antithymozyte globulins [ATGL] and / or Cylosporine) can reduce the morbidity and mortality, and also in the elderly, in patients with concomitant diseases and in those patients with suspected graft versus-host reaction (. such as those with multiple myeloma) sein.der useful transplantation after transplantation obtained transplant recipient colony stimulating factors, in order to shorten the duration of leukopenia occurring after transplantation; prophylactic drugs are administered to infection. The treatment after allogeneic HSC transplantation is up to 6 months in the prophylactic doses of immunosuppressants (usually methotrexate and cyclosporine), in order to prevent that donor T cells react against molecules of the HLA complex of the recipient (graft-versus-host -Illness). Unless a fever occurs, it is back gehaltend with the administration of broad-spectrum antibiotics in general. The addressing of the graft typically occurs 10-20 days after HSC transplantation (after stem cell transplantation is peripheral blood, the graft earlier) and is defined by the absolute neutrophil count> 500 x 106 / l. Complications of a stem cell transplant early stage (<100 days after transplantation) or occur later. After allogeneic HSC transplants the risk of infection is increased. Early complications Important early complications Missing engraftment rejection Acute graft-versus-host disease (GVHD) Lack of graft acceptance and rejection occur in <5% of patients and manifest as persistent pancytopenia or in an irreversible decrease in blood levels. Patients are treated for several weeks with Kortkcosteroiden. In recipients of allogeneic HSC transplantation may lead to an acute GVH disease; in transplant recipients of HLA-matched siblings, the incidence is 40%, and in transplant recipients from unrelated donors occurs in 80% of cases of acute GVH disease. Symptoms include fever, rashes, hepatitis with hyperbilirubinemia, vomiting, diarrhea, abdominal pain, which may progress to ileus, and weight loss. Risk factors for acute GVHD are HLA and sex mismatch with an unrelated donor Older age of recipient, donor, or both donor presensitization Insufficient GVHD prophylaxis The diagnosis of acute GVHD is made clear based on history, physical examination and results of liver function tests. Eel therapy methylprednisolone i.v. 2 mg / kg, 1 times a day administered. If the patient within 5 days does not respond to this dose, it is at 10 mg / kg erhöht.Spätkomplikationen Important late complications Chronic graft-versus-host disease (GVHD) GVHD Chronic recurrent can either occur spontaneously from acute GVHD or develop after their decay. They typically occurs 4-7 months after HSC transplantation on (the range is from 2 months to 2 years). Chronic GVHD occurs allogeneic HSC transplantation in recipients, of which about 35-50% have received a foreign donor graft an HLA-compatible transplant of a sibling and 60-70%. Chronic GVHD primarily affects the skin (z. B. papular eruption, scleroderma), and mucous membranes (eg. As keratoconjunctivitis sicca, periodontitis, orogenital lichenoid reactions), but also disorders of the gastrointestinal tract and the liver can occur. A primary characteristic is the immunodeficiency; Moreover, bronchiolitis obliterans may be similar to that as observed after lung transplantation, develop. Ultimately GVHD results in 20 to 40% of patients to death. Skin and mucosal diseases, treatment of GVHD is not absolutely necessary, while the treatment of more serious diseases such as in acute GVHD occurs. The incidence and severity of GVHD can be reduced by a T-cell depletion of allogeneic donor grafts using monoclonal antibodies or mechanical separation. With this method, but also a graft-tumor effect is eliminated, thereby increasing the stem cell proliferation and tackling graft and the rate of recurrence of the disease can be reduced. Recurrence rates of autologous HSC transplantation are higher because no graft-versus-tumor effect is present and possibly circulating tumor cells are transplanted. Studies on the purification of the graft ex vivo tumor cells prior to transplantation are underway. If no chronic GVHD occurs, all immunosuppressive therapies can be discontinued six months after HSC transplantation; d. H. that late complications in these patients rarely occur. Prognosis The prognosis after a stem cell transplant depends on the indication and method. A relapse occurs in 40 to 75% of recipients of autologous HSC grafts from 10 to 40% of recipients of allogeneic HSC transplants The success rates (no detection of cancer cells in the bone marrow) are 30 to 40% in patients with relapsed lymphoma that on chemotherapy react 20 to 50% in patients with acute leukemia in remission compared with chemotherapy alone, the HSC transplantation improves survival of patients with multiple myeloma. Patients with more advanced disease or with responsive solid cancers (eg. As germ cell tumors) have a lower success rate. In graft-vs-host disease "(GVHD), the relapse rates are lower, in severe GVHD but the mortality is increased overall. Intensive conditioning regimens, an effective GVHD prophylaxis, application of therapies Ciclosporinbasis and improved supportive treatment (eg. as antibiotics as needed, herpesvirus and cytomegalovirus prophylaxis) disease-free long-term survival rates have increased by HSC transplantation.

Health Life Media Team

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