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Acute and Late Toxicities with Total Marrow Irradiation

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Total Marrow Irradiation

Abstract

Total marrow with or without lymphoid irradiation (TM[L]I) is an approach that utilizes image-guided intensity-modulated radiation therapy to deliver a more targeted, organ sparing form of systemic radiotherapy or TBI. It is an approach either to dose escalate patients at higher-risk for relapse while maintaining acceptable organ doses or to incorporate radiation in a patient population that may not tolerate standard total body irradiation (TBI) as part of their conditioning regimen. The radiation-related toxicity profiles are, in general, favorable in TM(L)I compared to historical rates seen in TBI patient populations.

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References

  1. Shank B, O’Reilly RJ, Cunningham I, et al. Total body irradiation for bone marrow transplantation: the Memorial Sloan-Kettering Cancer Center experience. Radiother Oncol. 1990;18(Suppl 1):68–81.

    Article  PubMed  Google Scholar 

  2. Belkacémi Y, Pène F, Touboul E, et al. Total-body irradiation before bone marrow transplantation for acute leukemia in first or second complete remission. Results and prognostic factors in 326 consecutive patients. Strahlenther Onkol. 1998;174(2):92–104.

    Article  PubMed  Google Scholar 

  3. Ozsahin M, Pène F, Touboul E, et al. Total-body irradiation before bone marrow transplantation. Results of two randomized instantaneous dose rates in 157 patients. Cancer. 1992;69(11):2853–65.

    Article  CAS  PubMed  Google Scholar 

  4. Buchali A, Feyer P, Groll J, Massenkeil G, Arnold R, Budach V. Immediate toxicity during fractionated total body irradiation as conditioning for bone marrow transplantation. Radiother Oncol. 2000;54(2):157–62.

    Article  CAS  PubMed  Google Scholar 

  5. Valls A, Grañena A, Carreras E, Ferrer E, Algara M. Total body irradiation in bone marrow transplantation: fractionated vs single dose. Acute toxicity and preliminary results. Bull Cancer. 1989;76(8):797–804.

    CAS  PubMed  Google Scholar 

  6. Spitzer T, Friedman C, Bushnell W, Frankel S, Raschko J. Double-blind, randomized, parallel-group study on the efficacy and safety of oral granisetron and oral ondansetron in the prophylaxis of nausea and vomiting in patients receiving hyperfractionated total body irradiation. Bone Marrow Transplant. 2000;26(2):203–10.

    Article  CAS  PubMed  Google Scholar 

  7. Blume KG, Forman SJ, O’Donnell MR, et al. Total body irradiation and high-dose etoposide: a new preparatory regimen for bone marrow transplantation in patients with advanced hematologic malignancies. Blood. 1987;69(4):1015–20.

    Article  CAS  PubMed  Google Scholar 

  8. Moreau P, Facon T, Attal M, et al. Comparison of 200 mg/m(2) melphalan and 8 Gy total body irradiation plus 140 mg/m(2) melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myélome 9502 randomized trial. Blood. 2002;99(3):731–5.

    Article  CAS  PubMed  Google Scholar 

  9. Kelsey CR, Horwitz ME, Chino JP, et al. Severe pulmonary toxicity after myeloablative conditioning using total body irradiation: an assessment of risk factors. Int J Radiat Oncol. 2011;81(3):812–8.

    Article  Google Scholar 

  10. Kim TH, McGlave PB, Ramsay N, et al. Comparison of two total body irradiation regimens in allogeneic bone marrow transplantation for acute non-lymphoblastic leukemia in first remission. Int J Radiat Oncol Biol Phys. 1990;19(4):889–97.

    Article  CAS  PubMed  Google Scholar 

  11. Pino y Torres JL, Bross DS, Lam WC, Wharam MD, Santos GW, Order SE. Risk factors in interstitial pneumonitis following allogenic bone marrow transplantation. Int J Radiat Oncol Biol Phys. 1982;8(8):1301–7.

    Article  PubMed  Google Scholar 

  12. Cosset JM, Baume D, Pico JL, et al. Single dose versus hyperfractionated total body irradiation before allogeneic bone marrow transplantation: a non-randomized comparative study of 54 patients at the Institut Gustave-Roussy. Radiother Oncol. 1989;15(2):151–60.

    Article  CAS  PubMed  Google Scholar 

  13. Lohr F, Wenz F, Schraube P, et al. Lethal pulmonary toxicity after autologous bone marrow transplantation/peripheral blood stem cell transplantation for hematological malignancies. Radiother Oncol. 1998;48(1):45–51.

    Article  CAS  PubMed  Google Scholar 

  14. Gopal R, Ha CS, Tucker SL, et al. Comparison of two total body irradiation fractionation regimens with respect to acute and late pulmonary toxicity. Cancer. 2001;92(7):1949–58.

    Article  CAS  PubMed  Google Scholar 

  15. Sampath S, Schultheiss TE, Wong J. Dose response and factors related to interstitial pneumonitis after bone marrow transplant. Int J Radiat Oncol. 2005;63(3):876–84.

    Article  Google Scholar 

  16. Wong JYC, Rosenthal J, Liu A, Schultheiss T, Forman S, Somlo G. Image-guided total-marrow irradiation using helical tomotherapy in patients with multiple myeloma and acute leukemia undergoing hematopoietic cell transplantation. Int J Radiat Oncol. 2009;73(1):273–9.

    Article  Google Scholar 

  17. Somlo G, Spielberger R, Frankel P, et al. Total marrow irradiation: a new ablative regimen as part of tandem autologous stem cell transplantation for patients with multiple myeloma. Clin Cancer Res. 2011;17(1):174–82.

    Article  CAS  PubMed  Google Scholar 

  18. Shueng P-W, Lin S-C, Chong N-S, et al. Total marrow irradiation with helical tomotherapy for bone marrow transplantation of multiple myeloma: first experience in Asia. Technol Cancer Res Treat. 2009;8(1):29–37.

    Article  PubMed  Google Scholar 

  19. Lin S-C, Hsieh P-Y, Shueng P-W, Tien H-J, Wang L-Y, Hsieh C-H. Total marrow irradiation as part of autologous stem cell transplantation for Asian patients with multiple myeloma. Biomed Res Int. 2013;2013:1–7.

    Google Scholar 

  20. Patel P, Oh AL, Koshy M, et al. A phase 1 trial of autologous stem cell transplantation conditioned with melphalan 200 mg/m 2 and total marrow irradiation (TMI) in patients with relapsed/refractory multiple myeloma. Leuk Lymphoma. 2018;59(7):1666–71.

    Article  CAS  PubMed  Google Scholar 

  21. Rosenthal J, Wong J, Stein A, et al. Phase 1/2 trial of total marrow and lymph node irradiation to augment reduced-intensity transplantation for advanced hematologic malignancies. Blood. 2011;117(1):309–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Bearman SI, Appelbaum FR, Buckner CD, et al. Regimen-related toxicity in patients undergoing bone marrow transplantation. J Clin Oncol. 1988;6(10):1562–8.

    Article  CAS  PubMed  Google Scholar 

  23. Jensen LG, Stiller T, Wong JYC, Palmer J, Stein A, Rosenthal J. Total marrow lymphoid irradiation/fludarabine/melphalan conditioning for allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2018;24(2):301–7.

    Article  CAS  PubMed  Google Scholar 

  24. Stein A, Palmer J, Tsai N-C, et al. Phase I trial of total marrow and lymphoid irradiation transplantation conditioning in patients with relapsed/refractory acute leukemia. Biol Blood Marrow Transplant. 2017;23(4):618–24.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Patel P, Aydogan B, Koshy M, et al. Combination of linear accelerator–based intensity-modulated total marrow irradiation and myeloablative fludarabine/busulfan: a phase I study. Biol Blood Marrow Transplant. 2014;20(12):2034–41.

    Article  CAS  PubMed  Google Scholar 

  26. Hui S, Brunstein C, Takahashi Y, et al. Dose escalation of total marrow irradiation in high-risk patients undergoing allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2017;23(7):1110–6.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Corvò R, Zeverino M, Vagge S, et al. Helical tomotherapy targeting total bone marrow after total body irradiation for patients with relapsed acute leukemia undergoing an allogeneic stem cell transplant. Radiother Oncol. 2011;98(3):382–6.

    Article  PubMed  Google Scholar 

  28. Jiang Z, Jia J, Yue C, et al. Haploidentical hematopoietic SCT using helical tomotherapy for total-body irradiation and targeted dose boost in patients with high-risk/refractory acute lymphoblastic leukemia. Bone Marrow Transplant. 2018;53(4):438–48.

    Article  CAS  PubMed  Google Scholar 

  29. Kal HB, Van Kempen-Harteveld ML. Induction of severe cataract and late renal dysfunction following total body irradiation: dose-effect relationships. Anticancer Res. 2009;29(8):3305–9.

    PubMed  Google Scholar 

  30. Kersting S, Hené RJ, Koomans HA, Verdonck LF. Chronic kidney disease after myeloablative allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2007;13(10):1169–75.

    Article  PubMed  Google Scholar 

  31. Cheng JC, Schultheiss TE, Wong JYC. Impact of drug therapy, radiation dose, and dose rate on renal toxicity following bone marrow transplantation. Int J Radiat Oncol. 2008;71(5):1436–43.

    Article  CAS  Google Scholar 

  32. Berger C, Le-Gallo B, Donadieu J, et al. Late thyroid toxicity in 153 long-term survivors of allogeneic bone marrow transplantation for acute lymphoblastic leukaemia. Bone Marrow Transplant. 2005;35(10):991–5.

    Article  CAS  PubMed  Google Scholar 

  33. Farhadfar N, Stan MN, Shah P, et al. Thyroid dysfunction in adult hematopoietic cell transplant survivors: risks and outcomes. Bone Marrow Transplant. 2018;53(8):977–82.

    Article  CAS  PubMed  Google Scholar 

  34. Medinger M, Zeiter D, Heim D, et al. Hypothyroidism following allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia. Leuk Res. 2017;58:43–7.

    Article  CAS  PubMed  Google Scholar 

  35. Felicetti F, Manicone R, Corrias A, et al. Endocrine late effects after total body irradiation in patients who received hematopoietic cell transplantation during childhood: a retrospective study from a single institution. J Cancer Res Clin Oncol. 2011;137(9):1343–8.

    Article  PubMed  Google Scholar 

  36. van Kempen-Harteveld ML, Struikmans H, Kal HB, et al. Cataract-free interval and severity of cataract after total body irradiation and bone marrow transplantation: influence of treatment parameters. Int J Radiat Oncol Biol Phys. 2000;48(3):807–15.

    Article  PubMed  Google Scholar 

  37. van Kempen-Harteveld ML, van Weel-Sipman MH, Emmens C, 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(12):1151–6.

    Article  PubMed  Google Scholar 

  38. Curtis RE, Rowlings PA, Deeg HJ, et al. Solid cancers after bone marrow transplantation. N Engl J Med. 1997;336(13):897–904.

    Article  CAS  PubMed  Google Scholar 

  39. Bhatia S, Louie AD, Bhatia R, et al. Solid cancers after bone marrow transplantation. J Clin Oncol. 2001;19(2):464–71.

    Article  CAS  PubMed  Google Scholar 

  40. Bhatia S, Ramsay NK, Steinbuch M, et al. Malignant neoplasms following bone marrow transplantation. Blood. 1996;87(9):3633–9.

    Article  CAS  PubMed  Google Scholar 

  41. Chen C, Abraham R, Tsang R, Crump M, Keating A, Stewart A. Radiation-associated pneumonitis following autologous stem cell transplantation: predictive factors, disease characteristics and treatment outcomes. Bone Marrow Transplant. 2001;27(2):177–82.

    Article  CAS  PubMed  Google Scholar 

  42. Bölling T, Kreuziger DC, Ernst I, Elsayed H, Willich N. Retrospective, monocentric analysis of late effects after total body irradiation (TBI) in adults. Strahlentherapie und Onkol. 2011;187(5):311–5.

    Article  Google Scholar 

  43. Carruthers SA, Wallington MM. Total body irradiation and pneumonitis risk: a review of outcomes. Br J Cancer. 2004;90(11):2080–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Della Volpe A, Ferreri AJM, Annaloro C, et al. Lethal pulmonary complications significantly correlate with individually assessed mean lung dose in patients with hematologic malignancies treated with total body irradiation. Int J Radiat Oncol Biol Phys. 2002;52(2):483–8.

    Article  PubMed  Google Scholar 

  45. Savani BN, Montero A, Wu C, et al. Prediction and prevention of transplant-related mortality from pulmonary causes after total body irradiation and allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2005;11(3):223–30.

    Article  PubMed  Google Scholar 

  46. Esiashvili N, Lu X, Ulin K, et al. Higher reported lung dose received during total body irradiation for allogeneic hematopoietic stem cell transplantation in children with acute lymphoblastic leukemia is associated with inferior survival: a report from the Children’s Oncology Group. Int J Radiat Oncol Biol Phys. 2019;104(3):513–21.

    Article  PubMed  Google Scholar 

  47. Kim JH, Stein A, Tsai N, et al. Extramedullary relapse following total marrow and lymphoid irradiation in patients undergoing allogeneic hematopoietic cell transplantation. Int J Radiat Oncol. 2014;89(1):75–81.

    Article  Google Scholar 

  48. Hall MD, Schultheiss TE, Smith DD, Nguyen KH, Wong JYC. Dose response for radiation cataractogenesis: a meta-regression of hematopoietic stem cell transplantation regimens. Int J Radiat Oncol. 2015;91(1):22–9.

    Article  Google Scholar 

  49. Abugideiri M, Nanda RH, Butker C, et al. Factors influencing pulmonary toxicity in children undergoing allogeneic hematopoietic stem cell transplantation in the setting of total body irradiation-based myeloablative conditioning. Int J Radiat Oncol. 2016;94(2):349–59.

    Article  Google Scholar 

  50. Gao RW, Weisdorf DJ, DeFor TE, Ehler E, Dusenbery KE. Influence of total body irradiation dose rate on idiopathic pneumonia syndrome in acute leukemia patients undergoing allogeneic hematopoietic cell transplantation. Int J Radiat Oncol. 2019;103(1):180–9.

    Article  Google Scholar 

  51. Travis EL, Peters LJ, McNeill J, Thames HD, Karolis C. Effect of dose-rate on total body irradiation: lethality and pathologic findings. Radiother Oncol. 1985;4(4):341–51.

    Article  CAS  PubMed  Google Scholar 

  52. Weiner RS, Bortin MM, Gale RP, et al. Interstitial pneumonitis after bone marrow transplantation. Assessment of risk factors. Ann Intern Med. 1986;104(2):168–75.

    Article  CAS  PubMed  Google Scholar 

  53. Tarbell NJ, Amato DA, Down JD, Mauch P, Hellman S. Fractionation and dose rate effects in mice: a model for bone marrow transplantation in man. Int J Radiat Oncol Biol Phys. 1987;13(7):1065–9.

    Article  CAS  PubMed  Google Scholar 

  54. Zhuang AH, Liu A, Schultheiss TE, Wong JYC. Dosimetric study and verification of total body irradiation using helical tomotherapy and its comparison to extended SSD technique. Med Dosim. 2010;35(4):243–9.

    Article  PubMed  Google Scholar 

  55. Aydogan B, Yeginer M, Kavak GO, Fan J, Radosevich JA, Gwe-Ya K. Total marrow irradiation with RapidArc volumetric arc therapy. Int J Radiat Oncol. 2011;81(2):592–9.

    Article  Google Scholar 

  56. Springer A, Hammer J, Winkler E, et al. Total body irradiation with volumetric modulated arc therapy: dosimetric data and first clinical experience. Radiat Oncol. 2016;11:46.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Tas B, Durmus IF, Okumus A, et al. Total-body irradiation using linac-based volumetric modulated arc therapy: its clinical accuracy, feasibility and reliability. Radiother Oncol. 2018;129(3):527–33.

    Article  PubMed  Google Scholar 

  58. Gruen A, Ebell W, Wlodarczyk W, et al. Total body irradiation (TBI) using helical tomotherapy in children and young adults undergoing stem cell transplantation. Radiat Oncol. 2013;8(1):92.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Sarradin V, Simon L, Huynh A, Gilhodes J, Filleron T, Izar F. Total body irradiation using helical tomotherapy ® : treatment technique, dosimetric results and initial clinical experience. Cancer/Radiothérapie. 2018;22(1):17–24.

    Article  CAS  Google Scholar 

  60. Sullivan KM, Goldmuntz EA, Keyes-Elstein L, et al. Myeloablative autologous stem-cell transplantation for severe scleroderma. N Engl J Med. 2018;378(1):35–47.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA, USA

    Ashwin Shinde & Jeffrey Y. C. Wong

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  1. Ashwin Shinde
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  2. Jeffrey Y. C. Wong
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Correspondence to Ashwin Shinde or Jeffrey Y. C. Wong .

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Editors and Affiliations

  1. Department of Radiation Oncology, City Of Hope National Medical Center, Duarte, CA, USA

    Jeffrey Y. C. Wong

  2. Department of Radiation Oncology, City Of Hope National Medical Center, Duarte, CA, USA

    Susanta K. Hui

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Shinde, A., Wong, J.Y.C. (2020). Acute and Late Toxicities with Total Marrow Irradiation. In: Wong, J., Hui, S. (eds) Total Marrow Irradiation. Springer, Cham. https://doi.org/10.1007/978-3-030-38692-4_14

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  • DOI: https://doi.org/10.1007/978-3-030-38692-4_14

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