Non-Hodgkin’s Lymphoma High Dose Therapy

Part of the Medical Radiology book series (MEDRAD)


 In the past several decades, progress has been made in treatment of non-Hodgkin’s lymphoma with radiolabeled antibodies. Early work was performed using high doses of I-131 antibodies, followed by use of Y-90 labeled constructs. Specific radiolabeling techniques were developed for these uses. Principles of dosimetry estimation using imaging and other techniques were also developed for radiation absorbed dose estimation in dose escalation patient cohorts. Radiation safety guidelines and procedures also play an important role in this form of treatment. These involve specifics of patient care as well as protection of healthcare workers and providers. Clinical trials and results, as well as the comparison literature are reviewed and cited to provide a solid background for understanding high dose radioimmunotherapy in Non-Hodgkin’s lymphoma.


High Dose Chemotherapy Normal Organ Radiation Safety High Dose Therapy Autologous Stem Cell Rescue 
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  1. Baldissera RC, Nucci M, Vigorito AC et al (2006) Frontline therapy with early intensification and autologous stem cell transplantation versus conventional chemotherapy in unselected high-risk aggressive non-Hodgkin’s lymphoma patients: a prospective randomized GEMOH report. Acta Haematol 115(1–2):15–21PubMedCrossRefGoogle Scholar
  2. Behr TM, Griesinger F, Riggert J, Gratz S, Behe M, Kaufmann CC, Worman B, Brittinger G, Becker W (2002) High-dose myeloablative radioimmunotherapy of mantle cell non-Hodgkin lymphoma with the iodine-131-labeled chimeric anti-CD-20 antibody C2B8 and auotologous stem cell support. Results of a pilot study. Cancer 94(4 Suppl):1363–1372Google Scholar
  3. Cilley J, Winter JN (2006) Radioimmunotherapy and autologous stem cell transplantation for the treatment of B-cell lymphomas. Haematologica 91(1):114–120PubMedGoogle Scholar
  4. Corcoran MC, Eary J, Bernstein I, Press OW (1997) Radioimmunotherapy strategies for non-Hodgkin’s lymphomas. Ann Oncol 8(Suppl):S133–S138CrossRefGoogle Scholar
  5. Divizzi L, Guidetti A, Tarella C, Mange M, Metteucci P, Seregni E, Chiesa C, Bombardieri E, DiNicola M, Carlo-Stella C, Gianni AM (2008) High-dose Yttrium-90-Ibritumoab Tiuxetan with tandem stem-cell re-infusion: an outpatient preparative regimen for autologous hematopoetic cell transplantation. J Clin Oncol 26:5175–5182CrossRefGoogle Scholar
  6. Durack LD, Eary JF (1995) Data collection techniques for pre-radioimmunotherapy imaging. J Nucl Med Tech 23:65–69Google Scholar
  7. Eary JF, Appelbaum FL, Durack L, Brown P (1989) Preliminary validation of the opposing view method for quantitative gamma camera imaging. Med Phys 16(3):382–387PubMedCrossRefGoogle Scholar
  8. Eary JF, Press OW, Badger CC, Durack L, Richter KY, Addison SJ, Krohn KA, Fisher DR, Porter B, Williams DL, Martin P, Appelbaum FR, Levy R, Brown S, Miller R, Nelp W, Bernstein ID (1990) Imaging and treatment of B-cell lymphoma. J Nucl Med 31(8):1257–1268PubMedGoogle Scholar
  9. Eary JF, Pollard KR, Durack LD, Bice AN, Lewellen TK, Matthews D, Press OW, Nelp WB, Appelbaum FR, Bernstein I (1994) Post therapy imaging in high dose I-131 radioimmunotherapy patients. Med Phys 21(7):1157–1162PubMedCrossRefGoogle Scholar
  10. Eary JF, Krohn KA, Press OW, Durack L, Bernstein I (1997) Importance of pre-treatment radiation absorbed dose estimation for radioimmunotherapy of non-Hodgkin’s lymphoma. Nucl Med Biol 24(7):635–638PubMedCrossRefGoogle Scholar
  11. Elton MA, Jemal A, Mbulaiteye SM, Devese SS, Biggar RJ (2002) Trends in Kaposi’s sarcoma and non-Hodgkin’s lymphoma incidence in the United States from 1973 through 1998. J Natl Cancer Inst 94(16):1204–1210CrossRefGoogle Scholar
  12. Fisher DR, Badger CC, Breitz H, Eary JF, Durham JS, Hui TE, Hill RL, Nelp WB (1991) Internal radiation dosimetry for clinical testing of radiolabeled monoclonal antibodies. Antib Immunoconj Radiopharm 4(4):655–664Google Scholar
  13. Fisher RI, LeBlanc M, Press OW, Maloney DG, Unger JM, Miller TP (2005) New treatment options have changed the survival of patient with follicular lymphoma. J Clin Oncol 23(33):8447–8452PubMedCrossRefGoogle Scholar
  14. Gisselbrecht C, Vose J, Nademanee A, Gianni AM, Nagler A (2009) Radioimmunotherapy for stem cell transplantation in non-Hodgkin’s lymphoma: in pursit of a complete response. Oncologist 14(suppl 3):41–51PubMedCrossRefGoogle Scholar
  15. Gopal AK, Gooley TA, Maloney DG, Petersdorf SH, Eary JF, Rajendran JG, Bush SA, Durack LD, Golden J, Martin PJ, Matthews DC, Appelbaum FR, Bernstein ID, Press OW (2003) High-dose radioimmunotherapy versus conventional high-dose therapy and autologous hematopoietic stem cell transplantation for relapsed follicular non-Hodgkin lymphoma: a multivariable cohort analysis. Blood. Oct 1;102(7):2351-7. Epub 2003 May 15Google Scholar
  16. Gopal AK, Rajendran JG, Gooley TA, Pagel JM, Fisher DR, Petersdorf SH, Maloney DG, Eary JF, Appelbaum FR, Press OW (2007) High-dose [131I]Tositumomab (anti-CD20) Radioimmunotherapy and Autologous Hematopoietic Stem-Cell Transplantation for Adults > = 60 Years Old With Relapsed or Refractory B-Cell Lymphoma. J Clin Oncol. 2007 Apr 10;25911) 1396−1402Google Scholar
  17. Gopal AK, Rajendran J, Petersdorf SH, Maloney DG, Eary J, Wood B, Gooley TA, Martin P, Matthews D, Appelbaum FR, Bernstein I, Press OW (2002) High dose chemo-radioimmunotherapy with autologous stem cell support for relapsed mantle cell lymphoma. Blood 99(9):3158–3162PubMedCrossRefGoogle Scholar
  18. Gopal AK, Pagel JM, Rajendran JG, Maloney DG, Appelbaum FR, sorror ML, Sandmaier BM, Storb R, Press OW (2006) Improving the efficacy of reduced intensity allogenic transplantation for lymphoma using radioimmunotherapy. Biol Blood Marrow Transplant 7:697–702CrossRefGoogle Scholar
  19. Hui TE, Fisher DR, Press OW, Eary JF, Weinstein JN, Badger CC, Bernstein ID (1992) Localized beta dosimetry of 131I-labeled antibodies in follicular lymphoma. Med Phys 19(1):97–104PubMedCrossRefGoogle Scholar
  20. Inwards DJ, Cliiey JC, Winer JN (2006) Radioimmunotherapeutic strategies in autologous hematopoietic stem-cell transplantation for malignant lymphoma. Best Pract Res Clin Haematol. 119(4):669–684CrossRefGoogle Scholar
  21. Kishore R, Eary JF, Krohn KA, Nelp WB, Menard TW, Beaumier PL, Hellstrom KE, Hellstrom I (1986) Autoradiolysis of iodinated monoclonal antibody preparations. J Nucl Med Biol 13(4):457–459Google Scholar
  22. Liu SY, Eary JF, Petersdorf SH, Martin PJ, Maloney DG, Appelbaum FR, Matthews DC, Bush SA, Durack LD, Fisher DR, Gooley TA, Bernstein ID, Press OW (1998) Follow-up of relapsed B-cell lymphoma patients treated with Iodine-131-labeled anti-CD20 antibody and autologous stem-cell rescue. J Clin Oncol 16(10):3270–3278PubMedGoogle Scholar
  23. McBaugh (1989) Deborah Masters thesis “Radiation Safety aspects of Radioimmunotherapy”. University of Washington Department of Health physicsGoogle Scholar
  24. Moskowitz CH (1999) Conventional treatments for non-Hodgkin’s lymphoma: the need for new therapies. J Nucl Med 40(11):1967–1968Google Scholar
  25. Nademanee A, Forman S, Molina A, Fung H, Smith D, Dagis A, Kwok C, Yamauchi D, Anderson A-L, Falk P, Krishnan A, Kirschbaum M, Kogut N, Nakamura R, O’Donnell M, Parker P, Popplewell L, Pullarkat V, Rodriguez R, Sahebi F, Smith E, Snyder D, Stein A, Spielberger R, Zain J, White C, Raubitschek A (2005) A phase 1/2 trial of high-dose yttrium-90-ibritumoab tiuxetan in combination with high-dose etoposide and cyclophosphamide followed by autologous stem cell transplantation in patient with poor-risk or relapsed non-Hodgkin lymphoma. Blood 106(8):2896–2902PubMedCentralPubMedCrossRefGoogle Scholar
  26. Pollard KR, Bice AN, Eary JF, Durack LD, Lewellen TK (1992) A method for imaging therapeutic doses of Iodine-131 with a clinical gamma camera. J Nucl Med 33(5):771–776PubMedGoogle Scholar
  27. Pollard KR, Lewellen TK, Kaplan MS, Haynor DR, Miyaoka RS, Eary JF, Durack LD (1996) Energy-based scatter corrections for scintillation camera images of iodine-131. J Nucl Med 37(12):2030–2037PubMedGoogle Scholar
  28. Press OW (1999) Radiolabeled antibody therapy of B-cell lymphomas. Semin Oncol 26(5 Suppl 14):58–65PubMedGoogle Scholar
  29. Press OW, Eary JF, Badger CC, Martin PJ, Appelbaum FR, Nelp WB, Krohn KA, Fisher D, Porter B, Thomas ED et al (1990) High dose radioimmunotherapy of B-cell lymphomas. Front Radiat Ther Oncol 24:204–213PubMedGoogle Scholar
  30. Press OW, Eary JF, Appelbaum FR, Martin PJ, Badger CC, Nelp WB, Glenn S, Butchko G, Fisher D, Porter B, Matthews DC, Fisher LD, Bernstein ID (1993a) Radiolabeled-antibody therapy of B-cell lymphoma with autologous bone marrow support. NEJM 329(17):1219–1224PubMedCrossRefGoogle Scholar
  31. Press OW, Eary J, Badger CC, Appelbaum FR, Wiseman G, Matthews D, Martin PJ, Bernstein ID (1993b) High-dose radio immunotherapy of lymphomas. Cancer Treat Res 68:13–22PubMedCrossRefGoogle Scholar
  32. Press OW, Eary JF, Appelbaum FR, Martin PJ, Nelp WB, Glenn S, Fisher DR, Porter B, Matthews DC, Gooley T, Bernstein ID (1995) Phase II trial of 131I–B1 (anti-CD20) antibody therapy with autologous stem cell transplantation for relapsed B cell lymphomas. Lancet 346(8971):336–340PubMedCrossRefGoogle Scholar
  33. Press OW, Eary JF, Gooley T, Gopal AK, Liu S, Rajendran JG, Maloney DG, Petersdorf S, Bush SA, Durack LD, Martin PJ, Fisher DR, Wood B, Borrow JW, Porter B, Smith JP, Matthews DC, Appelbaum FR, Bernstein ID (2000) A phase I/II trial of Iodine-131-Tositumomab (Anti-CD20), Etoposide, Cyclophosphamide, and autologous stem cell transplantation for relapsed B cell lymphoma. Blood 96(9):2934–2942PubMedGoogle Scholar
  34. Rajendran JG, Fisher DR, Gopal AK, Durack LD, Press OW, Eary JF (2004) High-dose (131)I-tositumomab (anti-CD20) radioimmunotherapy for non-Hodgkin’s lymphoma: adjusting radiation absorbed dose to actual organ volumes. J Nucl Med 45(6):1059–1064PubMedGoogle Scholar
  35. Shenoi J, Gopal AK, Press OW. Pagel JM. Recent advances in novel radioimunotherapeutic approaches for allogeneic hematopoetic cell transplantation. Curr Opin Oncol 2009 (epub ahead of print)Google Scholar
  36. Shimoni A, Nagler A (2007) Radioimmnotherapy and stem cell transplantation in the treatment of aggressive B-cell lymphoma. Leuk Lymphoma 48(11):2110–2120PubMedCrossRefGoogle Scholar
  37. Shipp MA, Abeloff MD, Antman KH et al (1999) International Consensus Conference on high-dose therapy with hematopoetic stem cell transplantation in aggressive non-Hodgkin’s lymphomas: a report of the jury. J Clin Oncol 17(1):423–429PubMedGoogle Scholar
  38. Winter JN, Inwards DJ, Spies S, Wiseman G, Patton D, Erwin W, Rademaker AW, Weitner BB, Willimas SF, Talman MS, Micallef I, Mehta J, Singhai S, Evans AM, Zimmer M, Molina A, White CA, Gordon LI (2009). Ytrrium-90 ibritumoab tiuxetan doses calculated to deliver up to 15 Gy to critical organs may be safely combined with high-dose BEAM and autologous transplantation in relapsed or refractory B-cell non-Hodgkin’s lymphoma. J Clin Oncol 27(10):1853–1859CrossRefGoogle Scholar
  39. Zhang M, Gopal AK (2008) Radioimmunotherapy based conditioning regimens for stem cell transplantation. Semin Hematol 45(2):118–125PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Division of Nuclear MedicineUniversity of Washington Medical CenterSeattleUSA

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