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Bone marrow transplantation (BMT) or hematopoietic stem cell transplantation (HSCT) is a medical procedure in the field of hematology and oncology that involves transplantation of hematopoietic stem cells (HSC). It is most often performed for people with diseases of the blood or bone marrow, or certain types of cancer. Bone marrow transplantation was pioneered in the 1970's by E. Donnall Thomas whose work was later recognized with a Nobel Prize in Physiology and Medicine. Dr. Thomas' work showed that bone marrow cells infused intravenously could repopulate the bone marrow and produce new blood cells. His work also reduced the likelihood of developing a life-threatening complication called Graft-versus-host disease (GVHD). However it remains a risky procedure and it is reserved for patients with life threatening diseases. Hematology is the branch of medicine that is concerned with blood and its disorders. ...
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An organ transplant is the transplantation of a whole or partial organ from one body to another (or from a donor site on the patients own body), for the purpose of replacing the recipients damaged or failing organ with a working one from the donor site. ...
Sketch of bone marrow and its cells Pluripotential hemopoietic stem cells or pluripotential hematopoietic stem cells (PHSCs) are stem cells found in the bone marrow. ...
When normal cells are damaged beyond repair, they are eliminated by apoptosis. ...
Dr. Edward Donnall (Don) Thomas (b. ...
Sir Edward Appletons medal Photographs of Nobel Prize Medals. ...
Bone marrow (or medulla ossea) is the tissue comprising the center of large bones. ...
A blood cell is any cell of any type normally found in blood. ...
Graft-versus-host disease is a common complication of allogeneic bone marrow transplantation. ...
Principles
Most recipients of HSCTs are leukemia patients or others who would benefit from treatment with high doses of chemotherapy or total body irradiation. Other patients who receive bone marrow transplants include pediatric cases where the patient has an inborn defect such as severe combined immunodeficiency or congenital neutropenia and was born with defective stem cells. Children or adults with aplastic anemia have lost their stem cells after birth and may not require such high doses of chemotherapy and irradiation prior to a transplant. In this case there is a greater need for immunosuppressive agents. Other conditions that bone marrow transplants are considered for include thalassemia major, sickle-cell disease, myelodysplastic syndrome, lymphoma, and multiple myeloma. Leukemia (leukaemia in Commonwealth English) is a cancer of the blood or bone marrow characterized by an abnormal proliferation of white blood cells (leukocytes). ...
Chemotherapy is the use of chemical substances to treat disease. ...
Irradiation is the process by which an item is exposed to radiation. ...
Pediatrics (also spelled paediatrics or pædiatrics) is the branch of medicine that deals with the medical care of infants and children. ...
Severe Combined Immunodeficiency, or SCID, is a genetic disorder in which both arms (B cells and T cells) of the adaptive immune system are crippled, due to a defect in one of several possible genes. ...
It has been suggested that Agranulocytosis be merged into this article or section. ...
Aplastic anemia is a condition where the bone marrow does not produce enough, or any, new cells to replenish the blood cells. ...
Immunosuppressive agents are a class of drugs which act to suppress the normal activity of the immune system. ...
Thalassemia (American English) (or Thalassaemia in British English) is an inherited disease of the red blood cells, classified as a hemoglobinopathy. ...
Sickle-shaped red blood cells Sickle cell disease is a general term for a group of related genetic disorders caused by sickle hemoglobin (Hgb S). ...
Lymphoma is a general term for malignancies of lymphocytes or, more rarely, of histiocytes. ...
Multiple myeloma (also known as MM, myeloma, plasma cell myeloma, or as Kahlers disease after Otto Kahler) is a presently incurable hematological malignancy of plasma cells, the cells of the immune system that produce antibodies. ...
Stem cell collection
Types of donors There are two major types of bone marrow transplantation. Autologous bone marrow transplantation involves isolation of HSC from a patient, storage of the stem cells in a freezer, medical treatment of the patient that destroys stem cells remaining in the body, and return of the patient's own stored stem cells to their body. Autologous transplants have the advantage of a lower risk of graft rejection, infection and GVHD. Allogeneic bone marrow transplantation involves two people, one is the (normal) donor and one is the (patient) recipient. Allogeneic HSC donors must have a tissue (HLA) type that matches the recipient and, in addition, the recipient requires immunosuppressive medications. Allogeneic transplant donors may be related (usually a sibling) or unrelated volunteers. The human lymphocyte antigen system (HLA) is the group of genes in the human major histocompatibility complex (MHC) that encodes the cell-surface antigen-presenting proteins. ...
Immunosuppression is the medical suppression of the immune system. ...
Donor selection A major limitation of allogeneic bone marrow transplantation is a shortage of donors. To avoid rejection of the transplanted stem cells or severe GVHD, the donor should have the same human leukocyte antigens (HLA) as the recipient. About 25 to 30 percent of potential HSCT recipients have an HLA-identical sibling. For other recipients, registries of volunteer unrelated donors can be quickly searched in order to find a potential HLA match. If an exact match cannot be found, a partially matched donor can be used. However, the use of mismatched donors may increase the risk of graft rejection or severe graft-versus-host disease. Transplant rejection is when the immune system of the recipient of a transplant attacks the transplanted organ or tissue. ...
Graft-versus-host disease is a common complication of allogeneic bone marrow transplantation. ...
The human lymphocyte antigen system (HLA) is the group of genes in the human major histocompatibility complex (MHC) that encodes the cell-surface antigen-presenting proteins. ...
Graft-versus-host disease is a common complication of allogeneic bone marrow transplantation. ...
A compatible donor is found by doing additional HLA-testing from the blood of potential donors. The HLA genes fall in two categories (Type I and Type II). In general, mismatches of the Type-I genes (i.e. HLA-A, HLA-B, or HLA-C) increase the risk of graft rejection. A mismatch of an HLA Type II gene (i.e. HLA-DR, or HLA-DQB1) increases the risk of GVHD. In addition a genetic mismatch as small as a single DNA base pair is significant so perfect matches require knowledge of the exact DNA sequence of these genes for both donor and recipient. Leading transplant centers currently perform testing for all five of these HLA genes before declaring that a donor and recipient are HLA-identical. Space-filling model of a section of DNA molecule Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions specifying the biological development of all cellular forms of life (and most viruses). ...
In molecular biology, two nucleotides on opposite complementary DNA or RNA strands that are connected via hydrogen bonds are called a base pair (often abbreviated bp). ...
Sources of HSC In the case of a bone marrow transplant (BMT), the HSC are removed from a large bone of the donor, typically the pelvis, through a large needle that reaches the center of the bone. The technique is referred as a bone marrow harvest and is performed with general anesthesia because literally hundreds of insertions of the needle are required to obtain sufficient material. Human male pelvis, viewed from front Human female pelvis, viewed from front The pelvis is the bony structure located at the base of the spine (properly known as the caudal end). ...
The word needle has several meanings: // Sewing Needles used for sewing In sewing, a needle is a long, slender, object with a pointed tip, usually made of metal. ...
Peripheral blood stem cells (PBSC) are now the most common source of stem cells for HSCT. PBSC are collected from the blood through a process known as apheresis. The donor's blood is withdrawn through a sterile needle in one arm and passed through a machine that removes white blood cells. The red blood cells (RBC) are returned to the donor. The peripheral stem cell yield is boosted with daily subcutaneous injections of filgrastim. Whole blood enters the centrifuge on the left and separates into layers so that selected components can be drawn off on the right. ...
White Blood Cells is also the name of a White Stripes album. ...
Human red blood cells Red blood cells are the most common type of blood cell and are the vertebrate bodys principal means of delivering oxygen to body tissues via the blood. ...
Granulocyte-Colony Stimulating Factor (G-CSF) is a glycoprotein, growth factor or cytokine produced by a number of different tissues to stimulate the bone marrow to produce granulocytes. ...
Umbilical cord blood is obtained when a mother donates her infant's umbilical cord and placenta after birth. Cord blood has a higher concentration of HSC than is normally found in adult blood. However the small quantity of blood obtained from an umbilical cord (typically about 50 mL, 2 Tbsp) makes it more suitable for tranplantation into small children than into adults. Newer techniques using ex-vivo expansion of cord blood units or the use of 2 cord blood units from different donors are being explored to allow cord blood transplants to be used in adults. Newborn at 45 seconds. ...
The placenta is an ephemeral (temporary) organ present only in female placental mammals during gestation (pregnancy). ...
Cord blood is human blood from the placenta and umbilical cord, which are left over after birth. ...
Storage of HSC Unlike other organs, bone marrow cells can be frozen for prolonged time periods (cryopreserved) without damaging too many cells. This is necessary for autologous HSC because the cells must be harvested months in advance of the transplant treatment. In the case of allogeneic transplants fresh HSC are preferred in order to avoid cell loss that might occur during the freezing and thawing process. Allogeneic cord blood is stored frozen at a cord blood bank because it is only obtainable at the time of childbirth. To cryopreserve HSC a preservative, DMSO, must be added and the cells must be cooled very slowly in a control rate freezer to prevent osmotic cellular injury during ice crystal formation. HSC may be stored for years in a cryofreezer which typically utilizes liquid nitrogen because it is non-toxic and it is very cold (boiling point -196°C.) Cord blood is human blood from the placenta and umbilical cord, which are left over after birth. ...
Both private and public cord blood banks have developed since in the mid- to late 1990s in response to the success of umbilical cord blood transplants in treating diseases of the blood and immune systems, such as Fanconis anemia and Leukemia. ...
Childbirth (also called labour, birth, partus or parturition) is the culmination of a human pregnancy with the emergence of a newborn infant from its mothers uterus. ...
Flash point 95 °C R/S statement R: 36/37/38 S: 26-37/39 RTECS number PV6210000 Supplementary data page Structure and properties n, εr, etc. ...
Osmosis is the diffusion of a solvent through a semipermeable membrane from a region of low solute concentration to a region of high solute concentration. ...
General Name, Symbol, Number nitrogen, N, 7 Chemical series nonmetals Group, Period, Block 15, 2, p Appearance colorless Atomic mass 14. ...
Conditioning regimens The chemotherapy or irradiation given immediately prior to a transplant is called the conditioning or preparative regimen. The purpose is to help eradicate the patients disease prior to the infusion of HSC and to suppress immune reactions. Chemotherapy drugs and radiation both damage DNA in the cell nucleus which kills rapidly dividing cells by triggering a self-destruct mechanism called apoptosis. Bone marrow cells divide frequently and are particularly sensitive to this treatment. The bone marrow can be ablated at doses that cause minimal injury to other tissues. In allogeneic transplants a combination of cyclophosphamide with busulfan or total body irradiation is commonly employed. This treatment also has immunosuppressive effect which prevents rejection of the HSC by the recipients immune system. Autologous transplants may also use these conditioning regimens but many other chemotherapy combinations can be used depending on the type of disease. Space-filling model of a section of DNA molecule Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions specifying the biological development of all cellular forms of life (and most viruses). ...
In cell biology, the nucleus (from Latin nucleus or nuculeus, kernel) is found in all eukaryotic cells that contains most of the cells genetic material. ...
The cell cycle, or cell division cycle, is the cycle of events in a eukaryotic cell from one cell division to the next. ...
Apoptosis In biology, apoptosis (from the Greek words apo = from and ptosis = falling, pronounced ap-a-tow-sis[1]) is one of the main types of programmed cell death (PCD). ...
Cyclophosphamide is a nitrogen mustard alkylating agent, used to treat various types of cancer and some autoimmune disorders. ...
Irradiation is the process by which an item is exposed to radiation. ...
Non-myeloablative allogeneic HSCT is a newer treatment approach which uses lower doses of chemotherapy and radiation which are too low to erradicate all of the bone marrow cells of a recipient. Instead non-myeloablative transplants rely on the graft versus tumor effect for their benefit. They do require high doses of immunosuppressive agents in the early stages of treatment. This leads to a state of mixed chimerism early after transplant where both recipient and donor HSC coexist in the bone marrow space. Decreasing doses of immunosuppressive therapy then allows donor T-cells to eradicate the remaining recipient HSC and to induce GVHD and the graft versus tumor effect. Immunosuppressive agents are a class of drugs which act to suppress the normal activity of the immune system. ...
In Greek mythology, the Chimera is a monstrous creature made of the parts of multiple animals. ...
T cells are a subset of lymphocytes that play a large role in the immune response. ...
Graft-versus-host disease is a common complication of allogeneic bone marrow transplantation. ...
Transplantation and engraftment HSC are infused into the blood stream of the recipient through an intravenous (i.v.) catheter, like any other i.v. fluid. The HSC briefly circulate in the blood stream and then home into the bone marrow spaces where they grow and start to produce blood cells. After several weeks of growth in the bone marrow, expansion of HSC and their progeny is sufficient to normalize the blood cell counts and alleviate the need for RBC and platelet transfusions. An intravenous drip in a hospital Intravenous therapy or IV therapy is the administration of liquid substances directly into a vein. ...
Human red blood cells Red blood cells are the most common type of blood cell and are the vertebrate bodys principal means of delivering oxygen from the lungs or gills to body tissues via the blood. ...
A 250 ml bag of newly collected platelets. ...
Side effects and complications Bone marrow transplantation is associated with a fairly high mortality (10% or higher), which limits its use in conditions that are themselves not essentially life-threatening. Major causes of complications are sepsis, graft-versus-host disease and veno-occlusive disease. Sepsis (in Greek Σήψις, putrefaction) is a serious medical condition caused by a severe infection. ...
Graft-versus-host disease is a common complication of allogeneic bone marrow transplantation. ...
Veno-occlusive disease (VOD) is a disease affecting the liver. ...
Regimen-related toxicity Regimen-related toxicities are side-effects of the high dose chemotherapy or irradiation used in ablative HSCT.
Severe liver injury is termed hepatic veno-occlusive disease (VOD). Elevated levels of bilirubin, hepatomegaly and fluid retention are clinical hallmarks of this condition. Initially thought to be a specific form of Budd-Chiari syndrome (i.e. thrombosis of the liver veins). There is now a greater appreciation of the generalized cellular injury and obstruction in hepatic vein sinuses, and it has thus been referred to as sinusoidal obstruction syndrome (SOS). Severe case are associated with a high mortality. Anticoagulants or defibrotide may be effective in reducing the severity of VOD but may also increase bleeding complications. Ursodiol has been shown to help prevent VOD, presumably by helping the flow of bile. Veno-occlusive disease (VOD) is a disease affecting the liver. ...
Bilirubin is a yellow breakdown product of haem (heme in American English). ...
Hepatomegaly is an enlargement of the liver (swelling). ...
In medicine (gastroenterology and hepatology), Budd-Chiari syndrome is the clinical picture caused by occlusion of the hepatic vein. ...
Thrombosis is the formation of a clot or thrombus inside a blood vessel, obstructing the flow of blood through the circulatory system. ...
An anticoagulant is a substance that prevents coagulation; that is, it stops blood from clotting. ...
Ursodiol (trade names Actigall, Ursofalk, Urso Forte) is a bile acid found in large quantities in bear bile; it also occurs naturally in human bile in smaller quantities. ...
Bile (or gall) is a bitter, greenish-yellow alkaline fluid secreted by the liver of most vertebrates. ...
Mucositis is the injury of the mucosal lining of the mouth and throat and is a common regimen-related toxicity following ablative HSCT regimens. It is usually not life-threatening but is very painful, and prevents eating and drinking. Mucositis is treated with pain medications plus intravenous infusions to prevent dehydration and malnutrition.
Infection Bone marrow transplantation usually requires that the recipient's own bone marrow is destroyed ("myeloablation"). Prior to "engraftment" patients may go for several weeks without appreciable numbers of white blood cells to help fight infection. This puts a patient at risk of infections, sepsis and septic shock despite prophylactic antibiotics. The immunosuppressive agents employed in allogeneic transplants for the prevention or treatment of GVHD further increase the risk of opportunistic infection for at least a year post-transplant. White Blood Cells is also the name of a White Stripes album. ...
An infection is the detrimental colonization of a host organism by a foreign species. ...
Sepsis (in Greek Σήψις, putrefaction) is a serious medical condition caused by a severe infection. ...
Septic shock is a serious medical condition causing such effects as multiple organ failure and death in response to infection and sepsis. ...
This page is a candidate to be moved to Wiktionary. ...
An antibiotic is a drug that kills or slows the growth of bacteria. ...
Immunosuppressive agents are a class of drugs which act to suppress the normal activity of the immune system. ...
Opportunistic infections are infections in immunodeficient patients caused by pathogens which are incapable of causing infection in immunocompetent individuals. ...
Graft versus host disease Graft-versus-host disease is an inflammatory disease that is unique to allogeneic transplantation. It is an attack of the "new" bone marrow's immune cells against the recipient's tissues. This can occur even if the donor and recipient are HLA-identical because the immune system can still recognize other differences between their tissues. Acute GVHD is defined as that which occurs in the first 3 months after transplantation and may involve the skin, intestine, or the liver. Corticosteroids are standard treatment, e.g. methylprednisolone (Solu-Medrol) or prednisone. Chronic GVHD may also develop after allogeneic transplant and is the major source of late complications. In addition to inflammation, chronic GVHD may lead to the development of fibrosis, or scar tissue, similar to scleroderma or other autoimmune diseases and may cause functional disablity, and the need for prolonged immunsuppressive therapy. Graft-versus-host disease is a common complication of allogeneic bone marrow transplantation. ...
Model of the layers of human skin In zootomy and dermatology, skin is an organ of the integumentary system composed of a layer of tissues that protect underlying muscles and organs. ...
The intestine is the portion of the alimentary canal extending from the stomach to the anus and, in humans and mammals, consists of two segments, the small intestine and the large intestine. ...
The liver is an organ in vertebrates, including humans. ...
In physiology, corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. ...
Methylprednisolone (molecular weight 374. ...
Prednisone is a synthetic corticosteroid drug which is usually taken orally and can be used for a large number of different conditions. ...
Scleroderma is a rare, chronic disease characterized by excessive deposits of collagen. ...
Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. ...
Graft versus tumor effect Leukemia patients who develop GVHD, particularly chronic GVHD, after an allogeneic transplant have a lower risk of their leukemia relapsing than those who do not develop any GVHD. This is due to a therapeutic immune reaction of the grafted donor lymphocytes against the diseased bone marrow of the recipient and is termed the graft versus leukemia or graft versus tumor effect. This lower rate of relapse accounts for the increased success rate of allogeneic transplants compared to transplants from identical twins, and indicates that allogeneic HSCT is a form of immunotherapy.
Conditions treated with BMT
Acquired Acute lymphocytic leukaemia (ALL), also known as acute lymphoblastic leukaemia is a cancer of the white blood cells, characterised by the overproduction and continuous multiplication of malignant and immature white blood cells (referred to as lymphoblasts) in the bone marrow. ...
Acute myelogenous leukemia (AML), also known as acute myeloid leukemia, is a cancer of the myeloid line of blood cells. ...
Aplastic anemia is a condition where the bone marrow does not produce enough, or any, new cells to replenish the blood cells. ...
Chronic myelogenous leukemia (or CML) is a form of chronic leukemia characterised by increased production of myeloid cells in the bone marrow. ...
Multiple myeloma (also known as MM, myeloma, plasma cell myeloma, or as Kahlers disease after Otto Kahler) is a presently incurable hematological malignancy of plasma cells, the cells of the immune system that produce antibodies. ...
The myelodysplastic syndromes (MDS, formerly known as preleukemia) are a diverse collection of haematological conditions united by ineffective production of blood cells. ...
Non-Hodgkins lymphoma is a type of cancer. ...
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease characterised by aplastic anemia, thrombosis and red urine in the morning due to breakdown of red blood cells. ...
Radiation poisoning, also called radiation sickness, is a form of damage to organic tissue due to excessive exposure to ionizing radiation. ...
A congenital disorder is a medical condition or defect that is present at or before birth (for example, congenital heart disease). ...
Adrenoleukodystrophy (ALD) is a degenerative disorder of the sheath covering nerve fibers, known as myelin. ...
Hurler syndrome, also known as mucopolysaccharidosis type I (MPS I), is a genetic disorder that results in the deficiency of alpha-L iduronidate, which is an enzyme that breaks down mucopolysaccharides. ...
Krabbe disease (also known as globoid cell leukodystrophy) is a rare, often fatal degenerative disorder that affects the nervous system. ...
Metachromatic leukodystrophy (MLD) is the most common form of a family of genetic diseases known as the leukodystrophies, diseases which affect the growth and/or development of myelin, the fatty covering which acts an an insulator around nerve fibres throughout the central and peripherial nervous systems . ...
Thalassemia (American English) (or Thalassaemia in British English) is an inherited disease of the red blood cells, classified as a hemoglobinopathy. ...
Inborn errors of metabolism comprise a large class of genetic diseases involving disorders of metabolism. ...
References - Socié, Gérard, et. al. (December 2001). Busulfan plus cyclophosphamide compared with total-body irradiation plus cyclophosphamide before marrow transplantation for myeloid leukemia: long-term follow-up of 4 randomized studies, Blood, 98(13): 3569-3574.Fulltext. PMID 11739158.
- Richardson PG, et. al. (December 2002). Multi-institutional use of defibrotide in 88 patients after stem cell transplantation with severe veno-occlusive disease and multisystem organ failure: response without significant toxicity in a high-risk population and factors predictive of outcome, Blood, 100(13): 4337-43. PMID 12393437
- Guglielmi, PT, et. al. (December 1995). Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma, New England Journal of Medicine, 333(23): 1540-5. PMID 7477169.
- Barker JN, et. al. (December 2005). Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy, Blood, 105(3): 1343-1347.Fulltext. PMID 15466923.
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