Total body irradiation explained

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]

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]

Notes and References

  1. Gore EM, Lawton CA, Ash RC, Lipchik RJ . Pulmonary function changes in long-term survivors of bone marrow transplantation . Int. J. Radiat. Oncol. Biol. Phys. . 36 . 1 . 67–75 . August 1996 . 8823260 . 10.1016/S0360-3016(96)00123-X.
  2. Soule BP . 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 . September 2007 . 17637691 . 10.1038/sj.bmt.1705771 . vanc. Simone NL . Savani BN . 3 . Ning . H . Albert . P S . Barrett . A J . Singh . A K. free .
  3. https://web.archive.org/web/20090730004606/http://www1.va.gov/emshg/docs/Radiological_Medical_Countermeasures_Indexed-Final.pdf Department of Homeland Security Working Group on Radiological Dispersal Device (RDD) Preparedness
  4. 2247650 . 18 Suppl 1 . Clinical basis for TBI fractionation . 1990 . Cosset JM, Girinsky T, Malaise E, Chaillet MP, Dutreix J . Radiother Oncol . 60–7 . 10.1016/0167-8140(90)90179-z.
  5. Thomas ED . Marrow transplantation for acute nonlymphoblastic leukemia in first remission . N. Engl. J. Med. . 301 . 11 . 597–9 . September 1979 . 381925 . 10.1056/NEJM197909133011109. vanc. Buckner CD . Clift RA . 3 . Fefer . Alexander . Johnson . F. Leonard . Neiman . Paul E. . Sale . George E. . Sanders . Jean E. . Singer . Jack W..
  6. Thomas ED . 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 . May 1982 . 7050046 . 10.1016/0360-3016(82)90083-9. vanc. Clift RA . Hersman J . 3 . Sanders . JE . Stewart . P . Buckner . CD . Fefer . A . McGuffin . R . Smith . JW.
  7. Kinsella TJ . 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 . December 1983 . 9463099 . 10.1016/0360-3016(83)90368-1. vanc. Glaubiger D . Diesseroth A . 3 . Makuch . R . Waller . B . Pizzo . P . Glatstein . E.
  8. Burdach S . 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 . August 2003 . 12915596 . 10.1200/JCO.2003.12.039 . vanc. Meyer-Bahlburg A . Laws HJ . 3 . Haase . R . Van Kaik . B . Metzner . B . Wawer . A . Finke . R . Göbel . U.
  9. Tichelli André, Rovó Alicia . 2013 . Fertility Issues Following Hematopoietic Stem Cell Transplantation . Expert Rev Hematol . 6 . 4. 375–388 . 10.1586/17474086.2013.816507. 23991924 . 25139582 .
    In turn citing: Salooja N, Szydlo RM, Socie G . etal . 2001 . Pregnancy outcomes after peripheral blood or bone marrow transplantation: a retrospective survey . Lancet . 358 . 9278. 271–276 . 10.1016/s0140-6736(01)05482-4. 11498213 . 20198750 .
  10. Sanders JE, Hawley J, Levy W . etal . 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 . 10.1182/blood.V87.7.3045.bloodjournal8773045 . 8639928 . free .

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