Biologic Effects of TBI
Purpose To review the biologic effects of total body irradiation (TBI) with regard to leukemic cell kill, immunosuppression, and toxicity to critical normal tissues of concern (lung, lens, kidney, liver).
Methods A review of the radiobiologic TBI literature was done and data analyzed for relationships to TBI parameters such as total dose, dose per fraction, and dose rate. The radiobiologic effects of testicular and splenic ”boost” irradiation were also examined. Comparisons of TBI-containing regimens to chemotherapy-only regimens were also done.
Results Highly fractionated or hyperfractionated TBI regimens to a high total dose have an advantage over single dose TBI in radiobiological studies for achieving a high malignant cell kill and good immunosuppression with minimal organ toxicity. Splenic “boosting” has survival value in at least one subset of CML patients undergoing transplant and testicular “boosting” has decreased testicular relapse. Randomized studies of TBI combined with VP-16 or cyclosphosphamide versus busulfan combined with cyclophosphamide either show an advantage to TBI (in AML in 1st CR) or no difference (in chronic phase CML).
Summary/Conclusion Radiobiological evidence supports the use of highly fractionated TBI to a high total dose (≥ 13 Gy) compared with single dose TBI (10 Gy). Splenic boosts for some CML patients and a testicular boost for all leukemias may offer an advantage when combined with TBI regimens. Randomized studies support the continued use of TBI for AML, and the equivalence of such regimens to chemotherapy-only regimens for CML, but long-term results are pending.
KeywordsToxicity Filtration Leukemia Pneumonia Fractionation
Unable to display preview. Download preview PDF.
- 1.Bortin MM, Horowitz MM, Rimm AA (1992) Progress report from the international bone marrow transplant registry. Bone Marrow Transpl 10:113–122Google Scholar
- 4.Shank B, Andreeff M, Li D (1983) Cell survival kinetics in peripheral blood and bone marrow during total body irradiation for marrow transplantation. Int J Rad Oncol Biol Phys 9:1613–1623Google Scholar
- 8.Vitale V, Scarpati D, Frassoni F, Corvo R (1989) Total body irradiation: single dose, fractions, dose rate. Bone Marrow Transpl 4 (Suppl 1):233–235Google Scholar
- 11.Deeg HJ, Sullivan KM, Buckner CD et al. (1986) Marrow transplantation for acute non lymphoblastic leukemia in first remission: toxicity and long-term follow-up of patients conditioned with single dose or fractionated total body irradiation. Bone Marrow Transpl 1:151–157Google Scholar
- 14.Belkacemi Y, Ozsahin M, Pene F et al. (1996) Influence of TBI technique prior to BMT in recipients with AML in first CR (CRi). (Abst.) Bone Marrow Transpl 17 (Suppl. 1): S19Google Scholar
- 15.Girinsky T, Socie G, Ammarguellat H et al. (1994) Consequences of two different doses to the lungs during a single dose of total body irradiation: results of a randomized study on 85 patients. Int J Rad Oncol Biol Phys 30:821–824Google Scholar
- 16.Shank B, Chu FCH, Dinsmore R et al. (1983) Hyperfractionated total body irradiation for bone marrow transplantation. Results in seventy-leukemia patients with allogeneic transplants. Int J Rad Oncol Biol Phys 9:1607–1611Google Scholar
- 17.Gratwhol A, Hermans J, Biezen AV et al. (1992) No advantage for patients who receive splenic irradiation before bone marrow transplantation for chronic myeloid leukaemia. Bone Marrow Transpl 10:147–152Google Scholar
- 18.Gratwohl A, Hermans J, Biezen AV et al. (1996) Splenic irradiation before bone marrow transplantation for chronic myeloid leukemia. (Abst.) Bone Marrow Transpl 17 (Suppl. 1): S61Google Scholar
- 19.Fruchtman S, Scigliano E, Isola L et al. (1995) Hyperfractionated total body irradiation (HF-TBI) and whole allogeneic marrow grafts: an intensive, safe, and highly efficacious approach to the cure of leukemia. (Abst.) Blood 86 (Suppl 1):945aGoogle Scholar
- 20.Schwerdtfeger R, Kirsch A, Sonntag S et al. (1993) Allogeneic bone marrow transplantation in chronic myeloid leukemia - what is the best conditioning regime? Bone Marrow Transpl 12 (Suppl 2):13Google Scholar
- 21.Miller G, Wagner JE, Vogel sang GB, Santos GW (1991) A randomized trial of busulfan-cyclophos-phamide (Bu-Cy) versus cyclophosphamide-total body irradiation (Cy-TBI) as preparative regimen for patients with chronic myelogenous leukemia (CML). (Abst.) Blood 78 (Suppl 1):291aGoogle Scholar
- 22.Devergie A, Blaise D, Attal M et al. (1995) Allogeneic bone marrow transplantation for chronic myeloid leukemia in first chronic phase: a randomized trial of busulfan-Cytoxan versus Cytoxan-total body irradiation as preparative regimen: a report from the French Society of Bone Marrow Graf (SFGM). Blood 85:2263–2268PubMedGoogle Scholar
- 24.Blume KG, Kopecky KJ, Henslee-Downey JP et al. (1993) A prospective randomized comparison of total body irradiation-etoposide versus busulfan-cyclophosphamide as preparatory regimens for bone marrow transplantation in patients with leukemia who were not in first remission. Blood 81:2187–2193PubMedGoogle Scholar
- 26.Blaise D, Maraninchi D, Archimbaud E et al. (1993) Allogeneic bone marrow transplantation for acute myeloid leukemia in first remission: a randomized trial of a busulfan-Cytoxan versus Cytoxan-total body irradiation as preparative regimen: report from the Groupe d’Etudes de la Greffe de Moelle Osseuse. Blood 79:2578–2582Google Scholar
- 27.Michel G, Gluckman E, Esperou-Bourdeau H et al. (1994) Allogeneic bone marrow transplantation for children with acute myeloblastic leukemia in first complete remission: impact of conditioning regimen without total-body irradiation - a report from the Société Française de Greffe de Moelle. J Clin Oncol 12:1217–1222PubMedGoogle Scholar
- 35.Thomas ED, Clift RA, Hersman J et al. (1982) Marrow transplantation for acute nonlympho-blastic leukemia in first remission using fractionated or single-dose irradiation. Int J Rad Oncol Biol Phys 8:817–821Google Scholar
- 37.Devergie A, Reiffers J, Vernant JP et al. (1990) Long-term follow-up after bone marrow transplantation for chronic myelogenous leukemia: factors associated with relapse. Bone Marrow Transpl 5:379–386Google Scholar
- 39.Sutton L, Kuentz M, Cordonnier C et al. (1993) Allogeneic bone marrow transplantation for adult acute lymphoblastic leukemia in first complete remission: factors predictive of transplant-related mortality and influence of total body irradiation modalities. Bone Marrow Transpl 12:583–589Google Scholar