Total body irradiation
Encyclopedia
Total body irradiation is a form of radiotherapy used primarily as part of the preparative regimen for haematopoietic stem cell (or bone marrow) transplantation. As the name implies, TBI involves irradiation of the entire body, though in modern practice the lung
s are often partially shielded to lower the risk of radiation-induced lung injury. Total body irradiation in the setting of bone marrow transplantation serves to destroy or suppress the recipient's immune system, preventing immunologic rejection
of transplanted donor bone marrow
or blood stem cells. Additionally, high doses of total body irradiation can eradicate residual cancer
cells in the transplant recipient, increasing the likelihood that the transplant will be successful.
Doses of total body irradiation used in bone marrow transplantation typically range from 10 to >12 Gy
. For reference, a dose of 4.5 Gy is fatal in 50% of exposed individuals without aggressive medical care. Such high total body doses are made possible by spreading the total dose out between several sessions, or "fractions," with an interval of time in between allowing other normal tissues some time to repair some of the damage caused. However, at these doses, total body irradiation both destroys the patient's bone marrow (allowing donor marrow to engraft) and kills residual cancer cells. Non-myeloablative bone marrow transplantation uses lower doses of total body irradiation, typically about 2 Gy, which do not destroy the host bone marrow but do suppress the host immune system sufficiently to promote donor engraftment.
In modern practice, total body irradiation is typically fractionated. Early research in bone marrow transplantation by E. Donnall Thomas
and colleagues demonstrated that this process of splitting TBI into multiple smaller doses resulted in lower toxicity and better outcomes than delivering a single, large dose.
In addition to its use in bone marrow transplantation, total body irradiation has been explored as a treatment modality for high-risk Ewing sarcoma
. However, subsequent findings suggest that TBI in this setting causes toxicity without improving disease control, and TBI is not currently used in the treatment of Ewing sarcoma outside of clinical trial
s.
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
s are often partially shielded to lower the risk of radiation-induced lung injury. Total body irradiation in the setting of bone marrow transplantation serves to destroy or suppress the recipient's immune system, preventing immunologic rejection
Transplant rejection
Transplant rejection occurs when transplanted tissue is rejected by the recipient's immune system, which destroys the transplanted tissue. Transplant rejection can be lessened by determining the molecular similitude between donor and recipient and by use of immunosuppressant drugs after...
of transplanted donor bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
or blood stem cells. Additionally, high doses of total body irradiation can eradicate residual cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
cells in the transplant recipient, increasing the likelihood that the transplant will be successful.
Doses of total body irradiation used in bone marrow transplantation typically range from 10 to >12 Gy
Gray (unit)
The gray is the SI unit of absorbed radiation dose of ionizing radiation , and is defined as the absorption of one joule of ionizing radiation by one kilogram of matter ....
. For reference, a dose of 4.5 Gy is fatal in 50% of exposed individuals without aggressive medical care. Such high total body doses are made possible by spreading the total dose out between several sessions, or "fractions," with an interval of time in between allowing other normal tissues some time to repair some of the damage caused. However, at these doses, total body irradiation both destroys the patient's bone marrow (allowing donor marrow to engraft) and kills residual cancer cells. Non-myeloablative bone marrow transplantation uses lower doses of total body irradiation, typically about 2 Gy, which do not destroy the host bone marrow but do suppress the host immune system sufficiently to promote donor engraftment.
In modern practice, total body irradiation is typically fractionated. Early research in bone marrow transplantation by E. Donnall Thomas
E. Donnall Thomas
Dr. Edward Donnall Thomas is an American physician, professor emeritus at the University of Washington, and director emeritus of the clinical research division at the Fred Hutchinson Cancer Research Center. In 1990 he shared the Nobel Prize in Physiology or Medicine with Joseph E. Murray for the...
and colleagues demonstrated that this process of splitting TBI into multiple smaller doses resulted in lower toxicity and better outcomes than delivering a single, large dose.
In addition to its use in bone marrow transplantation, total body irradiation has been explored as a treatment modality for high-risk Ewing sarcoma
Ewing sarcoma
Ewing sarcoma is a malignant round-cell tumour. It is a rare disease in which cancer cells are found in the bone or in soft tissue. The most common areas in which it occurs are the pelvis, the femur, the humerus, the ribs and clavicle....
. However, subsequent findings suggest that TBI in this setting causes toxicity without improving disease control, and TBI is not currently used in the treatment of Ewing sarcoma outside of clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s.