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Bone Marrow Transplants
Bone Marrow Transplants
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Bone Marrow Transplants
Bone marrow is located in the interior of the bones and produces white cells for the immune system, red cells for oxygen transportation, and platelets for blood clotting. There are two types of bone marrow. Red marrow consists of mainly hematopoietic tissue, and yellow marrow consists mainly of fat cells. At birth all marrow is red, but with age, half of it is transformed into yellow marrow. Red marrow is found mainly in the flat bones such as the pelvis, sternum, and cranium, and in the ends of long bones such as the femur and humerus. Here hematopoiesis takes place, which is the formation of blood cellular components.
Surgeon Dr. Hans Janovich performs a bone marrow harvest operation. The procedure consists of inserting a large-gauge syringe into an area of the hip and extracting the bone marrow. This autologous transplantation was performed in order to recreate and replenish T-cells and the white and red blood cells killed while the patient underwent chemotherapy. (U.S. Navy/Chad McNeeley)
Approximately 1011–1012 new blood cells are produced daily in order to maintain steady-state levels in the bloodstream. All blood cells derive from hematopoietic stem cells that reside in the red bone marrow. They give rise to different precursor cells that eventually will differentiate and become mature blood cells. The bone marrow stroma is made up of other cell types such as fibroblasts and cells involved in the formation of bone structure, such as osteoblasts and osteoclasts. They are indirectly involved in hematopoiesis by secreting growth factors and cytokines, which influence the development of different cell types.
Since the 1950s there has been tremendous development of the procedure whereby bone marrow is transplanted from a healthy donor to a patient in need of restored bone marrow function, and since the 1970s it has been in clinical use. In 1990, E. Donnal Thomas and Joseph E. Murray received the Nobel Prize in Physiology or Medicine for their pioneering work on bone marrow transplantation. Today this is mainly used for patients with diseases that originated in the bone marrow, such as acute leukemia, but an increasing number of patients are treated for a wide variety of other diseases. Bone marrow transplantation is today mainly synonymous with hematopoietic stem cell transplantation (HSCT) whereby the cells are harvested by a procedure called apheresis from the peripheral blood of a healthy donor or the patient prior to treatment. Apheresis is a technique in which a person’s blood is passed from a vein through a machine that sorts out the stem cells and then the blood is given back. The cells can also be harvested as bone marrow by aspiration from the pelvic bone or from the umbilical cord of newborn infants. This is mainly used for donations to siblings with malignant or inborn diseases, but donation to unrelated children and adults is also possible.
Allogeneic Transplantation
An allogeneic transplantation is a procedure whereby stem cells are transferred from a healthy person to a patient. Candidates for this regimen are mainly patients with cancer diseases of the blood, such as acute leukemias, in which conventional cytostatics has failed or the genetic profile of the disease predicts a poor prognosis. Other conditions treated with stem cell transplants include sickle-cell disease, myelodysplastic syndrome, and aplastic anemia. Children could be treated for diseases such as severe combined immunodeficiency (SCID) or congenital neutropenia.
Thorough investigations of both the patient and the donor are carried out in order to ensure that they could manage the treatment. This includes examination of vital organ function such as heart, lungs, and kidneys but also screening for diseases that could complicate the transplantation. The donor should preferably be a sibling or an unrelated donor with a matching HLA (human leukocyte antigen) profile. This is to ensure that the transplanted cells do not attack the patient’s tissues and cause graft-versus-host disease (GVHD). This could present as skin rash, impairment of liver function, or inflammation of the colon with severe diarrhea. Since there is always some minor mismatch between donor and recipient, the patient needs to take immunosuppressant drugs for at least a couple of months after transplantation in order to prevent GVHD.
There is one beneficial aspect of having a mild GVHD since the immune reaction carried out by the donors T lymphocytes against the diseased bone marrow then is believed to lower the risk of relapse. This is called graft-versus-leukemia effect (GVL). There are newer regimens in which doses of cytostatics and irradiation have been lowered in order to make use of the GVL effect by leaving a small part of the recipient’s bone marrow intact. An increasing number of patients are today getting a transplant from a sibling without full HLA match (haploidentical), thus facilitating the search for an acceptable donor. This is made possible by new techniques that decrease the risk of serious GVHD. The donor is given a short treatment in order to mobilize the stem cells from the bone marrow to the blood stream and the cells are then collected by apheresis. There is today a worldwide network with interconnected registers that makes it possible to search for unrelated donors. Depending on the time between apheresis and transplantation, the cells are collected and transported to the recipient either fresh or frozen. If there are any cells left after transplantation, they are usually frozen and stored for later use if the patient does not respond as expected after transplantation.
Before the transplantation, the patient is given different chemotherapeutic regimens, depending on diagnosis and sometimes also irradiation. The goal is to eradicate the disease and create the possibility for the donor cells to reestablish a new hematopoietic system. It is crucial that the patient be kept isolated after transplantation because the immune system is severely impaired and infections could easily arise. Prophylactic treatment against fungal and viral infections is given during this time and strict surveillance to detect and treat any bacterial infection is crucial. There is also need for blood and platelet transfusions because this production is also impaired. Another severe side effect is inflammation of the mucosal tissue in the mouth, and patients often need to get nutrition through a nasogastric tube.
Autologous Transplantation
An autologous transplantation could also be performed whereby cells are harvested from the patient’s own blood and then frozen in order to be re-transplanted after intensive chemotherapy treatment has been given. Today, this is standard treatment for patients with multiple myeloma and also widely used for lymphoma patients and many other solid tumors such as testicular cancer. Depending on diagnosis, different cytostatic regimens are given in order to eradicate the cancer cells as much as possible and to make the patient’s condition suitable for transplantation. This is followed by a treatment that mobilizes the stem cells to the blood stream in
