Abstract
TBI has been used widely in the setting of BMT over the past 3 decades. Early research demonstrated feasibility and efficacy in the myeloablative setting, in preparation first for allogenic BMT and later for autologous stem cell rescue. As experience with TBI increased, its dual roles of myeloablation and immunosuppression came to be recognized. Toxicity associated with myeloablative TBI remains significant, and this treatment is generally reserved for younger patients with excellent performance status. Reduced intensity conditioning regimens may be useful to provide immunosuppression for patients who are not candidates for myeloablative treatment. Efforts to reduce toxicity through protection of normal tissue using methods of normal tissue blocking and use of TLI, rather than TBI, continue. In the future, modalities such as helical tomotherapy, proton radiotherapy and radioimmunotherapy, may have roles in delivery of radiation to the BM and lymphoid structures with reduced normal tissue toxicity. With further investigation, these efforts may expand the therapeutic ratio associated with TBI, allowing safer delivery to a broader range of patients.
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References
Nowell PC, Cole LJ, Habermeyer JG, Roan PL . Growth and continued function of rat marrow cells in x-radiated mice. Cancer Res 1956; 16: 258–261.
Vos O, Davids JAG, Weyzen WWH, van Bekkum DW . Evidence for cellular hypothesis in radiation protection by bone marrow cells. Acta Physiol Pharmacol Neerland 1956; 4: 482–486.
Lindsley DL, Odell TT, Tausche FG . Implantation of functional erythropoietic elements following total-body irradiation. Proc Soc Exp Biol Med 1955; 90: 512–515.
Makinodan T . Circulating rat cells in lethally irradiated mice protected with rat bone marrow. Proc Soc Exp Biol Med 1956; 92: 174–179.
Barnes DWH, Corp MJ, Loutit JF, Neal FE . Treatment of murine leukaemia with x-rays and homologous bone marrow. Preliminary communication. Br Med J 1956; 2: 626–627.
Mathé G, Amiel JL, Schwarzenberg L, Catton A, Schneider M . Adoptive immunotherapy of acute leukemia: experimental and clinical results. Cancer Res 1965; 25: 1525–1531.
Andrews GA . Criticality accidents in Vinca, Yugoslavia, and Oak Ridge, Tennessee. Am J Roentgenol Radium Ther Nucl Med 1965; 93: 56–74.
Thomas ED, Storb R, Clift RA, Fefer A, Johnson FL, Neiman PE et al. Bone-marrow transplantation. N Engl J Med 1975; 292: 832–843, 895–902.
Thomas ED, Buckner CD, Banaji M, Clift RA, Fefer A, Flournoy N et al. One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation. Blood 1977; 49: 511–533.
Thomas ED, Buckner CD, Clift RA, Fefer A, Johnson FL, Neiman PE et al. Marrow transplantation for acute nonlymphoblastic leukemia in first remission. N Engl J Med 1979; 301: 597–599.
Thomas ED, Sanders JE, Flournoy N, Johnson FL, Buckner CD, Clift RA et al. Marrow transplantation for patients with acute lymphoblastic leukemia in remission. Blood 1979; 54: 468–476.
Keane TJ, Van Dyk J, Rider WD . Idiopathic interstitial pneumonia following bone marrow transplantation: the relationship with total body irradiation. Int J Radiat Oncol Biol Phys 1981; 7: 1365–1370.
Ravindranath Y, Yeager AM, Chang MN, Steuber CP, Krischer J, Graham-Pole J et al. Autologous bone marrow transplantation versus intensive consolidation chemotherapy for acute myeloid leukemia in childhood. Pediatric Oncology Group. N Engl J Med 1996; 334: 1428–1434.
Vaidya SJ, Atra A, Bahl S, Pinterton CR, Calvagna V, Horton C et al. Autologous bone marrow transplantation for childhood acute lymphoblastic leukaemia in second remission: long-term follow-up. Bone Marrow Transplant 2000; 25: 599–603.
Dusenberry KE, Daniels KA, McClure JS, McGlave PB, Ramsay NK, Blazar BR et al. Randomized comparison of cyclophosphamide-total body irradiation versus busulfan-cyclophosphamide conditioning in autologous bone marrow transplantation for acute myeloid leukemia. Int J Radiat Oncol Biol Phys 1995; 31: 119–128.
Biagi E, Rovelli A, De Lorenzo P, Uderzo C . Autologous hematopoetic stem cell transplantation (AHSCT) as consolidation therapy for childhood acute myelogenous leukemia in 1st complete remission. Pediatr Hematol Oncol 2001; 18: 359–362.
Ringdén O, Labopin M, Tura S, Arcese W, Iriondo A, Zittoun R et al. A comparison of Busulphan versus total body irradiation combined with cyclophosphamide as conditioning for autograft or allograft bone marrow transplantation in patients with acute leukaemia. Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Br J Haematol 1996; 93: 637–645.
Davies SM, Ramsay KC, Klein JP, Weisdorf DJ, Bolwell B, Cahn JY et al. Comparison of preparative regimens in transplants for children with acute lymphoblastic leukemia. J Clin Oncol 2000; 18: 340–347.
Kröger N, Zabelina T, Krüger W, Renges H, Stute N, Kabisch H et al. Comparison of total body irradiation vs busulfan in combination with cyclophosphamide as conditioning for unrelated stem cell transplantation in CML patients. Bone Marrow Transplant 2001; 27: 349–354.
Shi-Xia X, Xian-Hua T, Hai-Qin X, Bo F, Xiang-Feng T . Total body irradiation plus cyclophosphamide versus busulphan with cyclophosphamide as conditioning regimen for patients with leukemia undergoing allogeneic stem cell transplantation: a meta-analysis. Leuk Lymphoma 2010; 51 (1): 50–60.
Altschuler C, Resbeut M, Blaise D, Maraninchi D, Stoppa AM, Lagrange JL et al. Fractionated total body irradiation and bone marrow transplantation in acute lymphoblastic leukemia. Int J Radiat Oncol Biol Phys 1990; 19: 1151–1154.
Gale RP, Butturini A, Bortin MM . What does total body irradiation do in bone marrow transplants for leukemia? Int J Radiat Oncol Biol Phys 1991; 20: 631–634.
Gough MJ, Crittenden MR . Combination approaches to immunotherapy: the radiotherapy example. Immunotherapy 2009; 1 (6): 1025–1037.
Kim TH, Rybka WB, Lehnert S, Podgorsak EB, Freeman CR . Interstitial pneumonitis following total body irradiation for bone marrow transplantation using two different dose rates. Int J Radiat Oncol Biol Phys 1985; 11: 1285–1291.
Barrett AJ . Bone marrow transplantation. Cancer Treat Rev 1987; 14: 203–213.
Barrett AJ, Depledge MH, Powles RL . Interstitial pneumonitis following bone marrow transplantation after low dose rate total body irradiation. Int J Radiat Oncol Biol Phys 1983; 9: 1029–1033.
Cosset JM, Girinsky T, Malaise E, Chaillet MP, Dutreix J . Clinical basis for TBI fractionation. Radiother Oncol 1990; 18 (Suppl 1): 60–67.
Shank B, Chu FC, Dinsmore R, Kapoor N, Kirkpatrick D, Teitelbaum H et al. Hyperfractionated total body irradiation for bone marrow transplantation. Results in seventy leukemia patients with allogeneic transplants. Int J Radiat Oncol Biol Phys 1983; 9: 1607–1611.
Thomas ED, Clift RA, Hersman J, Sanders JE, Stewart P, Buckner CD et al. Marrow transplantation for acute nonlymphoblastic leukemia in first remission using fractionated or single-dose irradiation. Int J Radiat Oncol Biol Phys 1982; 8: 817–821.
Katz R, Sharma SC, Homayoonfar M . Irradiation equivalence. Health Phys 1972; 23: 740–741.
Clift RA, Buckner CD, Appelbaum FR, Bearman SI, Petersen FB, Fisher LD et al. Allogeneic bone marrow transplantation in patients with acute myeloid leukemia in first remission: a randomized trial of two irradiation regimens. Blood 1990; 76: 1867–1871.
Clift RA, Buckner CD, Appelbaum FR, Sullivan KM, Storb R, Thomas ED . Long-term follow-up of a randomized trial of two irradiation regimens for patients receiving allogeneic marrow transplants during first remission of acute myeloid leukemia. Blood 1998; 92: 1455–1456.
Clift RA, Buckner CD, Appelbaum FR, Bryant E, Bearman SI, Petersen FB et al. Allogeneic marrow transplantationin patients with chronic myeloid leukemia in the chronic phase: a randomized trial of two irradiation regimens. Blood 1991; 77: 1660–1665.
Bieri S, Helg C, Chapuis B, Miralbell R . Total body irradiation before allogeneic bone marrow transplantation: is more dose better? Int J Radiat Oncol Biol Phys 2001; 18: 1071:1077.
Giralt S, Estey E, Albitar M, van Besien K, Rondón G, Anderlini P et al. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood 1997; 89: 4531–4536.
McSweeney PA, Niederwieser D, Shizuru JA, Sandmaier BM, Molina AJ, Maloney DG et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood 2001; 97: 3390–3400.
Sorror ML, Maris MB, Storer B, Sandmaier BM, Diaconescu R, Flowers C et al. Comparing morbidity and mortality of HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative and myeloablative conditioning: influence of pretransplantation comorbidities. Blood 2004; 104: 961–968.
Mielcarek M, Martin PJ, Leisenring W, Flowers ME, Maloney DG, Sandmaier BM et al. Graft-versus-host disease after nonmyeloablative versus conventional hematopoietic stem cell transplantation. Blood 2003; 102: 756–762.
Baron F, Maris MB, Sandmaier BM, Storer BE, Sorrer M, Diaconescu R et al. Graft-versus-tumor effects after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning. J Clin Oncol 2005; 23: 1993–2003.
Kahl C, Storer BE, Sandmaier BM, Mielcarek M, Maris MB, Blume KG et al. Relapse risk in patients with malignant diseases given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. Blood 2007; 110: 2744–2748.
Baron F, Maris MB, Storer BE, Sandmaier BM, Stuart MJ, McSweeney PA et al. HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with chronic myeloid leukemia. Biol Blood Marrow Transplant 2005; 11: 272–279.
Marks DI, Wang T, Pérez WS, Antin JH, Copelan E, Gale RP et al. The outcome of full-intensity and reduced-intensity conditioning matched sibling or unrelated donor transplantation in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first and second complete remission. Blood 2010; 116: 366–374.
Pecego R, Hill R, Appelbaum FR, Amos D, Buckner CD, Fefer A et al. Interstitial pneumonitis following autologous bone marrow transplantation. Transplantation 1986; 42: 515–517.
Deeg HJ . Delayed complications and long-term effects after bone marrow transplantation. Hematol Oncol Clin North Am 1990; 4: 641–657.
Benyunes MC, Sullivan KM, Deeg HJ, Mori M, Meyer W, Fisher L et al. Cataracts after bone marrow transplantation: long-term follow-up of adults treated with fractionated total body irradiation. Int J Radiat Oncol Biol Phys 1995; 32: 661–670.
Tauchmanovà L, Selleri C, DeRosa G, Pagano L, Orio F, Lombarde G et al. High prevalence of endocrine dysfunction in long-term survivors after allogeneic bone marrow transplantation for hematologic diseases. Cancer 2002; 95: 1076–1084.
Gerstein J, Meyer A, Sykora KW, Frühauf J, Karstens JH, Bremer M . Long-term renal toxicity in children following fractionated total-body irradiation (TBI) before allogeneic stem cell transplantation (SCT). Strahlenther Onkol 2009; 185: 751–755.
Abboud I, Porcher R, Robin M, de Latium RP, Glotz D, Socié G et al. Chronic kidney dysfunction in patients alive without relapse 2 years after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2009; 15: 1251–1257.
Benmiloud S, Steffens M, Beauloye V, de Wandeleer A, Devogelaer JP, Brichard B et al. Long-term effects on bone mineral density of different therapeutic schemes for acute lymphoblastic leukemia or non-hodgkin lymphoma during childhood. Horm Res Paediatr 2010; 74: 241–250.
Brand HS, Bots CP, Raber-Durlacher JE . Xerostomia and chronic oral complications among patients treated with haematopoietic stem cell transplantation. Br Dent J 2009; 207: E17.
Ishida Y, Sakamoto N, Kamibeppu K, Kakee N, Iwai T, Ozono S et al. Late effects and quality of life of childhood cancer survivors: Part 2. Impact of radiotherapy. Int J Hematol 2010; 92 (1): 95–104.
Chow EJ, Simmons JH, Roth CL, Baker KS, Hoffmeister PA, Sanders JE et al. Increased cardiometabolic traits in pediatric survivors of acute lymphoblastic leukemia treated with total body irradiation. Biol Blood Marrow Transplant 2010 (e-pub ahead of print).
Ayash LJ, Hunt M, Antman K, Nadler L, Wheeler C, Takvorian T et al. Hepatic veno-occlusive disease in autologous bone marrow transplantation of solid tumors and lymphomas. J Clin Oncol 1990; 8: 1699–1706.
Cutler C, Stevenson K, Kim HT, Richardson P, Ho VT, Linden E et al. Sirolimus is associated with veno-occlusive disease of the liver after myeloablative allogeneic stem cell transplantation. Blood 2008; 112 (12): 4425–4431.
Carreras E . Veno-occlusive disease of the liver after hematopoetic cell transplantation. Eur J Haematol 2000; 64 (5): 281–291.
Kusumi E, Kami M, Kanda Y, Murashige N, Seki K, Fujiwara M . Hepatic injury following reduced intensity unrelated cord blood transplantation for adult patients with hematological diseases. Biol Blood Marrow Transplant 2006; 12: 1302–1309.
Rizzo JD, Curtis RE, Socié G, Sobocinski KA, Gilbert E, Landgren O et al. Solid cancers after allogeneic hematopoetic cell transplantation. Blood 2009; 113: 1175–1183.
Curtis RE, Rowlings PA, Deeg HJ, Shriner DA, Socié G, Travis LB et al. Solid cancers after bone marrow transplantation. N Engl J Med. 1997; 336 (13): 897–904.
Socié G, Curtis RE, Deeg HJ, Sobocinski KA, Filipovich AH, Travis LB et al. New malignant diseases after allogeneic marrow transplantation for childhood acute leukemia. J Clin Oncol 2000; 18: 348–357.
Krishnan A, Bhatia S, Slovak ML, Arber DA, Niland JC, Nademanee A et al. Predictors of therapy-related leukemia and myelodysplasia following autologous transplantation for lymphoma: an assessment of risk factors. Blood 2000; 95: 1588–1593.
Janssen WJ, Muldrow A, Kearns MT, Barthel L, Henson PM . Development and characterization of a lung-protective method of bone marrow transplantation in the mouse. J Immunol Methods 2010; 357: 1–9.
Singh AK, Karimpour SE, Savani BN, Guion P, Hope AJ, Mansueti JR et al. Pretransplant pulmonary function tests predict risk of mortality following fractionated total body irradiation and allogeneic peripheral blood stem cell transplant. Int J Radiat Oncol Biol Phys 2006; 66 (2): 520–527.
van Kempen-Harteveld ML, van Weel-Sipman MH, Emmens C, Noordijk EM, van der Tweel I, Révész T et al. Eye shielding during total body irradiation for bone marrow transplantation in children transplanted for a hematological disorder: risks and benefits. Bone Marrow Transplant 2003; 31: 1151–1156.
Broerse JJ, Dutriex A, Noordijk EM . Physical, biological, and clinical aspects of TBI. Radiother Oncol 1990; 18 (Suppl 1): 11–162.
Harden SV, Routsis DS, Geater AR, Thomas SJ, Coles C, Taylor PJ et al. Total body irradiation using a modified standing technique: a single institution 7 year experience. Br J Radiol 2001; 74: 1041–1047.
Lan F, Zeng D, Higuchi M, Huie P, Higgins JP, Strober S . Predominance of NK1.1+TCR alpha beta+ or DX5+TCR alpha beta+ T cells in mice conditioned with fractionated lymphoid irradiation protects against graft-versus-host disease: ‘natural suppressor’ cells. J Immunol 2001; 167: 2087–2096.
Lan F, Zeng D, Higuchi M, Higgins JP, Strober S . Host conditioning with total lymphoid irradiation and antithymocyte globulin prevents graft-versus-host disease: the role of CD1-reactive natural killer T cells. Biol Blood Marrow Transplant 2003; 9: 355–363.
Hoffmann P, Ermann J, Edinger M, Fathman CG, Strober S . Donor-type CD4(+) CD25(+) regulatory T cells suppress lethal acute graft-versus-host disease after allogeneic bone marrow transplantation. J Exp Med 2002; 196: 389–399.
Lowsky R, Takahashi T, Liu YP, Dejbakhsh-Jones S, Grumet FC, Shizuru JA et al. Protective conditioning for acute graft-versus-host disease. New Engl J Med 2005; 353 (13): 1321–1331.
Schaenman JM, Shashidhar S, Rhee C, Wong J, Navato S, Wong RM et al. Early CMV viremia is associated with impaired viral control following nonmyeloablative hematopoetic cell transplantation with a total lymphoid irradiation and antithymocyte globulin preparative regimen. Biol Blood Marrow Transplant 2010 (e-pub ahead of print).
Nakamae H, Terada Y, Nakane T, Koh H, Nakamae M, Aimoto R et al. A modified myeloablative conditioning regimen for allogeneic hematopoietic stem cell transplantation, consisting of intravenous busulfan, cyclophosphamide and total lymphoid irradiation, in advanced leukemia. Gan To Kagaku Ryoho 2010; 37: 1691–1695.
Zhuang AH, Liu A, Schultheiss T, Wong YC . Dosimetric study and verification of total body irradiation using helical tomotherapy and its comparison to extended SSD technique. Medical Dosimetry (e-pub ahead of print).
Wong JY, Liu A, Schultheiss T, Popplewell L, Stein A, Rosenthal J et al. Targeted total marrow irradiation using three-dimensional image-guided tomographic intensity-modulated radiation therapy: an alternative to standard total body irradiation. Biol Blood Marrow Transplant 2006; 12: 306–315.
Lee CT, Bilton SD, Famiglietti RM, Riley BA, Mahajan A, Chang EL et al. Treatment planning with protons for pediatric retinoblastoma, medulloblastoma, and pelvic sarcoma: how do protons compare with other conformal techniques? Int J Radiat Oncol Biol Phys 2005; 63: 362–372.
Timmermann B, Lomax AJ, Nobile L, Grotzer MA, Weiss M, Kortmann RD et al. Novel technique of craniospinal axis proton therapy with the spot-scanning system: avoidance of patching multiple fields and optimized ventral dose distribution. Strahlenther Onkol 2007; 183: 685–688.
Bethge WA, Lange T, Meisner C, von Harsdorf S, Bornhaeuser M, Federmann B et al. Radioimmunotherapy with yttrium-90-ibritumomab tiuxetan as part of a reduced-intensity conditioning regimen for allogeneic hematopoietic cell transplantation in patients with advanced non-Hodgkin lymphoma: results of a phase 2 study. Blood 2010; 116 (10): 1795–1802.
Barbet J, Chatal JF, Kraeber-Bodéré F . Radiolabeled antibodies for cancer treatment. Med Sci (Paris) 2009; 25: 1039–1045.
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Hill-Kayser, C., Plastaras, J., Tochner, Z. et al. TBI during BM and SCT: review of the past, discussion of the present and consideration of future directions. Bone Marrow Transplant 46, 475–484 (2011). https://doi.org/10.1038/bmt.2010.280
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DOI: https://doi.org/10.1038/bmt.2010.280
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