Bone marrow transplant
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Bone marrow transplantation (BMT) is a hematological medical procedure that involves stem cell transplantation. The common feature of recipients is a need for blood stem cells. It is a dangerous procedure, associated with a mortality over 10%, and can be complicated by infection and graft-versus-host disease.
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Principles
Engraftment
Most recipients of BMTs are leukemia patients or others who have been exposed to high doses of chemotherapy or total body irradiation resulting in destruction of their bone marrow stem cells. 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 either no blood stem cells or defective stem cells. Other conditions that bone marrow transplants are considered for include thalassemia major, sickle cell disease, aplastic anemia and myelodysplastic syndrome.
The transplanted cells are bone marrow-derived blood stem cells. These cells can be obtained from a bone marrow donation, peripheral blood donation or donation of the blood from an umbilical cord and placenta after a baby is born.
Donation
In a bone marrow donation, bone marrow is surgically removed from a large bone of the donor, typically the sternum or the hip, by a large needle that reaches the center of the bone. The technique is referred as a bone marrow harvest and involves literally 100s of insertions of the needle.
Peripheral blood cells are collected 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 The donor's blood is withdrawn through a sterile needle in one arm and passed through a machine that separates the blood-forming cells. The rest of the blood is returned to the donor. Usually, peripheral stem cell yield is stimulated with daily subcutaneous G-CSF. This procedure is rapidly replacing traditional bone marrow donation.
Cord blood is obtained when a mother donates her infant's umbilical cord and placenta after birth. The blood products obtained are either transplanted immediately or frozen for later use. The blood stem cells are infused into the recipient through an IV (intravenous) line, like any other intravenous fluid. The blood stem cells will eventually settle into the recipient's bone and start producing blood cells over there.
There are two major types of bone marrow transplantation. Allogeneic bone marrow transplantation involves two people, one is the donor and one is the recipient. Autologous bone marrow transplantation involves isolation of bone marrow-derived blood stem cells from a patient, storage of the stem cells, 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.
Donor limitation
A major limitation of allogeneic bone marrow transplantation is a shortage of donors. To avoid rejection of the transplanted stem cells, the donor should have the same human leukocyte antigens as the recipient. About 25 to 30 percent of bone marrow transplantation recipients have an HLA-identical sibling who donates the required stem cells. For other recipients, registries of volunteer donors can be quickly searched in order to find an exact HLA match. If an exact match cannot be found, HLA-similar donors can be used. However, the results with non-exact donors are sometimes poor due to rejection or severe graft-versus-host disease.
A compatible donor is found by doing blood tests on potential donors. Perfect matches, the donor matches on all six HLA types result in the most successful transplants. Less perfect matches, four or five matches, can also result in successful transplants but the risk of complications is greater.
Side-effects and complications
Bone marrow transplantation is associated with a fair 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.
Infection
Bone marrow transplantation usually requires that the recipient's own bone marrow is destroyed ("myeloablation"). This is done with high-dose chemotherapy (e.g. busulfan). This puts a patient at risk of infections, sepsis and septic shock. While antibiotics are commonly administered prophylactically, this is still the major complication of transplantation.
GvHD
Graft-versus-host disease is an attack of the "new" bone marrow's immune cells against the recipient's tissues. This can affect any organ, but the skin and intestine, as well as the liver, typically suffer. Prednisolone and other immune suppressants are often necessary.
VOD
Veno-occlusive disease is an enigmatic complication that develops in the liver; extreme levels of bilirubin are the hallmark of this condition. Initially thought to be a specific form of Budd-Chiari syndrome (i.e. thrombosis of the liver veins), it is now thought to be swelling of the wall of liver blood vessels, with obstruction of outflowing blood. It has a high mortality. Anticoagulants are sometimes effective in reducing the severity of VOD; defibrotide in particular is used.
Conditions treated with BMT
- Acute lymphocytic leukemia
- Acute myelogenous leukemia
- Aplastic anemia
- Thalassemia
- Radiation poisoning
- Chronic myelogenous leukemia - accelerated phase or blast crisis
- Paroxysmal nocturnal hemoglobinuria (PNH) - severe aplasia
- Non-Hodgkin's lymphoma
- Myelodysplasia
- Multiple myeloma
External links
- The Merck Manual of Diagnosis and Therapy (http://www.merck.com/mrkshared/mmanual/section12/chapter149/149h.jsp) bone marrow transplantation page.
- Cancer Medicine (http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?rid=cmed.chapter.15785) online textbook.
- Bone Marrow Transplantation and Peripheral Blood Stem Cell Transplantation: Questions and Answers (http://cis.nci.nih.gov/fact/7_41.htm). National Cancer Institute.
- Bone Marrow Donors Worldwide (http://www.bmdw.org/)
- The Bone Marrow Foundation (http://www.bonemarrow.org/)
- U.S. National Marrow Donor Program (http://www.marrow.org/)
- Blood & Marrow Transplant Information Network (http://www.bmtnews.org/)
- Anthony Nolan Trust (http://www.anthonynolan.org.uk/)de:Knochenmarktransplantation