Total body irradiation

Total body irradiation (TBI) 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 lungs are often partially shielded to lower the risk of radiation-induced lung injury.[1][2] 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.

Dosage

Doses of total body irradiation used in bone marrow transplantation typically range from 10 to >12 Gy. For reference, an unfractionated (i.e. single exposure) dose of 4.5 Gy is fatal in 50% of exposed individuals without aggressive medical care.[3] The 10-12 Gy is typically delivered across multiple fractions to minimise toxicities to the patient.[4]

In modern practice, total body irradiation is typically fractionated, with smaller doses delivered in several sessions, rather than delivering the entire dose at once. 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.[5][6] The time interval between fractions allows other normal tissues some time to repair some of the damage caused. However, the dosing is still high enough that the ultimate result is the destruction of both the patient's bone marrow (allowing donor marrow to engraft) and any 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.

Usage in other cancers

In addition to its use in bone marrow transplantation, total body irradiation has been explored as a treatment modality for high-risk Ewing sarcoma.[7] However, subsequent findings suggest that TBI in this setting causes toxicity without improving disease control,[8] and TBI is not currently used in the treatment of Ewing sarcoma outside of clinical trials.

Fertility

Total body irradiation results in infertility in most cases, with recovery of gonadal function occurring in 10−14% of females. The number of pregnancies observed after hematopoietic stem cell transplantation involving such a procedure is lower than 2%.[9] Fertility preservation measures mainly include cryopreservation of ovarian tissue, embryos or oocytes. Gonadal function has been reported to recover in less than 20% of males after TBI.[10]

References
  1. Gore EM, Lawton CA, Ash RC, Lipchik RJ (August 1996). "Pulmonary function changes in long-term survivors of bone marrow transplantation". Int. J. Radiat. Oncol. Biol. Phys. 36 (1): 67–75. doi:10.1016/S0360-3016(96)00123-X. PMID 8823260.
  2. Soule BP, Simone NL, Savani BN, et al. (September 2007). "Pulmonary function following total body irradiation (with or without lung shielding) and allogeneic peripheral blood stem cell transplant". Bone Marrow Transplant. 40 (6): 573–8. doi:10.1038/sj.bmt.1705771. PMID 17637691.
  3. Department of Homeland Security Working Group on Radiological Dispersal Device (RDD) Preparedness, from the United States Department of Homeland Security. Accessed May 29, 2008.
  4. Cosset JM, Girinsky T, Malaise E, Chaillet MP, Dutreix J (1990). "Clinical basis for TBI fractionation". Radiother Oncol. 18 Suppl 1: 60–7. doi:10.1016/0167-8140(90)90179-z. PMID 2247650.CS1 maint: multiple names: authors list (link)
  5. Thomas ED, Buckner CD, Clift RA, et al. (September 1979). "Marrow transplantation for acute nonlymphoblastic leukemia in first remission". N. Engl. J. Med. 301 (11): 597–9. doi:10.1056/NEJM197909133011109. PMID 381925.
  6. Thomas ED, Clift RA, Hersman J, et al. (May 1982). "Marrow transplantation for acute nonlymphoblastic leukemic in first remission using fractionated or single-dose irradiation". Int. J. Radiat. Oncol. Biol. Phys. 8 (5): 817–21. doi:10.1016/0360-3016(82)90083-9. PMID 7050046.
  7. Kinsella TJ, Glaubiger D, Diesseroth A, et al. (December 1983). "Intensive combined modality therapy including low-dose TBI in high-risk Ewing's Sarcoma Patients". Int. J. Radiat. Oncol. Biol. Phys. 9 (12): 1955–60. doi:10.1016/0360-3016(83)90368-1. PMID 9463099.
  8. Burdach S, Meyer-Bahlburg A, Laws HJ, et al. (August 2003). "High-dose therapy for patients with primary multifocal and early relapsed Ewing's tumors: results of two consecutive regimens assessing the role of total-body irradiation". J. Clin. Oncol. 21 (16): 3072–8. doi:10.1200/JCO.2003.12.039. PMID 12915596.
  9. Tichelli André, Rovó Alicia (2013). "Fertility Issues Following Hematopoietic Stem Cell Transplantation". Expert Rev Hematol. 6 (4): 375–388. doi:10.1586/17474086.2013.816507. PMID 23991924.
    In turn citing: Salooja N, Szydlo RM, Socie G; et al. (2001). "Pregnancy outcomes after peripheral blood or bone marrow transplantation: a retrospective survey". Lancet. 358 (9278): 271–276. doi:10.1016/s0140-6736(01)05482-4. PMID 11498213.CS1 maint: multiple names: authors list (link)
  10. Sanders JE, Hawley J, Levy W; et al. (1996). "Pregnancies following high-dose cyclophosphamide with or without high-dose busulfan or total-body irradiation and bone marrow transplantation". Blood. 87 (7): 3045–52. doi:10.1182/blood.V87.7.3045.bloodjournal8773045. PMID 8639928.CS1 maint: multiple names: authors list (link)
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