Skip to main content
SpringerLink
Log in

Myeloablative Radiolabeled Antibody Therapy with Autologous Bone marrow Transplantation for Relapsed B Cell Lymphomas

  • Chapter
Technical and Biological Components of Marrow Transplantation

Part of the book series: Cancer Treatment and Research ((CTAR,volume 76))

Abstract

In spite of recent advances in radiation therapy and combination chemotherapy, patients with relapsed non-Hodgkin’s lymphomas are currently incurable with conventional treatments. Investigators at many institutions, including our own, have studied the potential of supralethal doses of chemoradiotherapy in conjunction with allogeneic or autologous bone marrow transplantation to cure patients with relapsed lymphomas [1–12]. A variety of marrow transplant conditioning regimens have been investigated, including high-dose cyclophosphamide plus total body irradiation (TBI); busulfan plus cyclophosphamide; busulfan, cyclophosphamide, and TBI; TBI and high-dose cytarabine; cyclophosphamide, bis-chloroethyl-nitrosourea (BCNU), and etoposide; and cyclophosphamide, etoposide, and TBI [1–12]. None of these regimens has demonstrated clear superiority. Most regimens yield long-term disease-free survival rates of 40–50% for patients transplanted in early first relapse or second remission and 10–20% for patients transplanted with more advanced disease. Although these results are superior to those achievable with any standard chemotherapeutic approach, over half of the transplanted patients still die of lymphomatous relapse. Further dose escalation to decrease relapse rates is not feasible because of lethal toxicities, such as interstitial lung disease, veno-occlusive disease of the liver, and renal failure, which kill 5–15% of patients treated with existing regimens.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Appelbaum FR, Sullivan KM, Buckner CD, et al.: Treatment of malignant lymphoma in 100 patients with chemotherapy, total body irradiation, and marrow transplantation. J Clin Oncol 5:1340, 1987.

    PubMed  CAS  Google Scholar 

  2. Freedman AS, Takvorian T, Neuberg D, et al.: Autologous bone marrow transplantation in poor-prognosis intermediate-grade and high-grade B-cell non-Hodgkin’s lymphoma in first remission: A pilot study. J Clin Oncol 11:931, 1993.

    PubMed  CAS  Google Scholar 

  3. Takvorian T, Canellos GP, Ritz J, et al.: Prolonged disease-free survival after autologous bone marrow transplantation in patients with non-Hodgkin’s lymphoma with a poor-prognosis. N Engl J Med 316:1499, 1987.

    Article  PubMed  CAS  Google Scholar 

  4. Horning SJ, Chao NJ, Negrin RS, et al.: The Stanford experiment with high-dose etoposide cytoreductive regimens and autologous bone marrow transplantation in Hodgkin’s disease and non-Hodgkin’s lymphoma: Preliminary data. Ann Oncol 2:47, 1991.

    PubMed  Google Scholar 

  5. Philip T, Armitage JO, Spitzer G, et al.: High-dose therapy and autologous bone marrow transplantation after failure of conventional chemotherapy in adults with intermediate-grade or high-grade non-Hodgkin’s lymphoma. N Engl J Medi 316:1494, 1987.

    Google Scholar 

  6. Armitage JO: Bone marrow transplantation for indolent lymphomas. Semin Oncol 20:136, 1993.

    PubMed  CAS  Google Scholar 

  7. Petersen FB, Buckner CD, Appelbaum FR, Sanders JE, Bensinger WI, Storb R, Deeg HJ, Witherspoon RP, Sullivan KM, Clift RA, et al.: Etoposide, cyclophosphamide and fractionated total body irradiation as a preparative regimen for marrow transplantation in patients with advanced hematological malignancies: a phase I study. Bone Marrow Transplant 10:83, 1992.

    PubMed  CAS  Google Scholar 

  8. Van der Jagt RH, Appelbaum FR, Petersen FB, Bigelow CL, Fisher LD, Schoch GH, Buckner CD, Sanders JE, Storb R, Sullivan KM, et al.: Busulfan and cyclophosphamide as a preparative regimen for bone marrow transplantation in patients with prior chest radiotherapy. Bone Marrow Transplant 3:211–1991.

    Google Scholar 

  9. Petersen FB, Appelbaum FR, Hill R, Fisher LD, Bigelow CL, Sanders JE Sullivan KM, Bensinger WI, Witherspoon RP, Storb R, et al.: Autologous marrow transplantation for malignant lymphoma: A report of 101 cases from Seattle. J Clin Oncol 8:638, 1990.

    PubMed  CAS  Google Scholar 

  10. Petersen FB, Appelbaum FR, Bigelow CL, Buckner CD, Clift RA, Sanders JE, Storb R, Sullivan KM, Weiden PL, Fefer A, et al.: High-dose cytosine arabinoside, total body irradiation and marrow transplantation for advanced malignant lymphoma. Bone Marrow Transplant 4:483, 1989.

    PubMed  CAS  Google Scholar 

  11. Weaver CH, Appelbaum FR, Petersen FB, Clift R, Singer J, Press O, Bensinger W, Bianco J, Martin P, Anasetti C, et al.: High-dose cyclophosphamide, carmustine, and etoposide followed by autologous bone marrow transplantation in patients with lymphoid malignancies who have received dose-limiting radiation therapy. J Clin Oncol 7:1329, 1993.

    Google Scholar 

  12. Bearman SI, Appelbaum FR, Back A, Petersen FB, Buckner CD, Sullivan KM, Schoch HG, Fisher LD, Thomas ED: Regimen-related toxicity and early posttransplant survival in patients undergoing marrow transplantation for lymphoma. J Clin Oncol 9:1288, 1989.

    Google Scholar 

  13. Grossbard M, Press O, Appelbaum F, Bernstein I, Nadler L: Monoclonal antibody-based therapies of leukemia and lymphoma. Blood 80:863, 1992.

    PubMed  CAS  Google Scholar 

  14. Press OW, Eary J, Appelbaum F, et al.: Radiolabeled-antibody therapy of B-cell lymphoma with autologous bone marrow support. N Engl J Med 329:1219, 1993.

    Article  PubMed  CAS  Google Scholar 

  15. Press OW, Eary J, Badger C, Appelbaum FR, Martin PJ, Levy R, Miller R, Brown S, Nelp WB, Krohn KA, Fisher D, DeSantes K, Porter B, Kidd P, Thomas ED, Bernstein ID: Treatment of patients with refractory non-Hodgkin’s lymphomas with radiolabeled MB-1 (anti-CD37) antibody. J Clin Oncol 7:1027, 1989.

    PubMed  CAS  Google Scholar 

  16. Press OW, Eary J, Appelbaum F, Badger C, Bernstein I. ‘High dose radioimmunotherapy with marrow transplantation’. In Rosen S, Kuzul T (eds): Immunoconjugate Therapy of Hematologic Malignancies. Boston: Kluwer Academic, 1993, p 13.

    Chapter  Google Scholar 

  17. Foon KA, Schroff RW, Gale RP: Surface markers on leukemia and lymphoma cells: Recent advances. Blood 60:1, 1982.

    PubMed  CAS  Google Scholar 

  18. Horibe K, Nadler LM: Human B cell associated antigens defined by monoclonal antibodies. In Heise ER (ed): Lymphocyte Surface Antigens, New York, ASHI, 1984, pp 309–323.

    Google Scholar 

  19. Barclay AN, Birkeland ML, Brown MH: The Leukocyte Antigen Facts Book. San Diego, CA: Academic Press, 1993.

    Google Scholar 

  20. Kaminski MS, Zasadny KR, Francis IR, et al.: Radioimmunotherapy of B-cell lymphoma with 1-131 anti-Bl (anti-CD20) antibody. N Engl J Med 329:459, 1993.

    Article  PubMed  CAS  Google Scholar 

  21. Meeker TC, Lowder J, Maloney DG, et al.: A clinical trial of anti-idiotype therapy for B cell malignancy. Blood 65:1349, 1985.

    PubMed  CAS  Google Scholar 

  22. Shawler DL, Bartholomew RM, Smith LM, et al.: Human immune response to multiple injections of murine monoclonal IgG. J Immunol 135:1530, 1985.

    PubMed  CAS  Google Scholar 

  23. Press OW, Eary JF, Appelbaum FR, et al.: Treatment of relapsed B cell lymphomas with high-dose radioimmunotherapy and bone marrow transplantation. In Goldenberg D (ed): Cancer Therapy with Radiolabeled Antibodies. Boca Raton, Fl: CRC Press, in press.

    Google Scholar 

  24. Press OW, Eary JF, Appelbaum FR, Bernstein ID: Radiolabeled antibody therapy of lymphomas. In De Vita V, Hellman S, Rosenberg SA (eds): Biologic Therapy of Cancer Updates. Philadelphia: JB Lippincott, 1994, pp 1–13.

    Google Scholar 

  25. Press OW, Eary JF, Appelbaum FR, et al.: Radiolabeled antibody therapy of lymphoma. In Dana B (ed): Malignant Lymphomas, Including Hodgkin’s Disease: Diagnosis, Management and Special Problems. Boston: Kluwer Academic, 1993, p 127.

    Chapter  Google Scholar 

  26. Nourigat C, Badger CC, Bernstein I: Treatment of lymphoma with radiolabeled antibody: Elimination of tumor cells lacking target antigen. J Natl Cancer Inst 82:47, 1990.

    Article  PubMed  CAS  Google Scholar 

  27. Leunig M, Yuan F, Menger MD, et al.: Angiogenesis, microvascular architecture, micro-hemodynamics and interstitial fluid pressure during early growth of human adenocarcinoma LS174T in SCID mice. Cancer Res 52:6553, 1992.

    PubMed  CAS  Google Scholar 

  28. Roselli M, Schlom J, Gansow OA, et al.: Comparative biodistribution of yttrium-and indium-labeled monoclonal antibody B72.3 in athymic mice bearing human colon carcinoma xenografts. J Nuclear Med 30:672, 1989.

    CAS  Google Scholar 

  29. Raubitschek AA: Yttrium-90 labeled T101 in the treatment of hematologic malignancies. Proceedings of the Fifth International Conference on Monoclonal Antibody Conjugates for Cancer, 1990.

    Google Scholar 

  30. Hnatowich DJ: Label stability in serum of four radionuclides on DPTA-coupled antibodies — An evaluation. Nuclear Med Biol 13:353, 1986.

    CAS  Google Scholar 

  31. Gansow OA: Newer approaches to the radiolabeling of monoclonal antibodies by use of metal chelates. Int J Radiat Appli Instrument 18:369, 1991.

    CAS  Google Scholar 

  32. Kosmas C, Snook D, Gooden CS, et al.: Development of humoral immune responses against a macrocyclic chelating agent (DOTA) in cancer patients receiving radioimmuno-conjugates for imaging and therapy. Cancer Res 52:904, 1992.

    PubMed  CAS  Google Scholar 

  33. Buchsbaum DJ, Lawrence TS, Roberson PL, et al.: Comparison of 1-131 and Y-90 labeled monoclonal antibody 17-1A for treatment of human colon cancer xenografts. Int J Radiat Oncpl Biol Phys 25:629, 1993.

    Article  CAS  Google Scholar 

  34. Buchsbaum DJ, Langmuir VK, Wessels BW: Experimental radioimmunotherapy. Med Phys 20:551, 1993.

    Article  PubMed  CAS  Google Scholar 

  35. Sharkey RM, Motta-Hennessy C, Pawlyk D, et al.: Biodistribution and radiation dose estimates for yttrium-and iodine-labeled monoclonal antibody IgG and fragments in nude mice bearing human colonic tumor xenografts. Cancer Res 50:2330, 1990.

    PubMed  CAS  Google Scholar 

  36. Boven E, Lindmo T, Mitchell JB, et al.: Selective cytotoxicity of I-125-labeled monoclonal antibody T101 in human malignant T cell lines. Blood 67:429, 1986.

    PubMed  CAS  Google Scholar 

  37. Woo DV, Li D, Mattis JA, et al.: Selective chromosomal damage and cytotoxicity of 1-125 labeled monoclonal antibody 17-1A in human cancer cells. Cancer Res 49:2952, 1989.

    PubMed  CAS  Google Scholar 

  38. Order SE, Stillwagon GB, Klein JL, et al.: Iodine 131 anti-ferritin, a new treatment modality in hepatoma: A Radiation Therapy Oncology Group Study. J Clin Oncol 3:1573, 1985.

    PubMed  CAS  Google Scholar 

  39. Vriesendorp HM, Herpst JM, Germack MA, et al.: Phase I-II studies of yttrium-labeled antiferritin treatment for end-stage Hodgkin’s disease, including Radiation Therapy Oncology Group 87-01. J Clin Oncol 9:918, 1991.

    PubMed  CAS  Google Scholar 

  40. Kohler G, Milstein C: Continuous cultures of fused cells secreting antibody of predefined specifity. Nature 256:495, 1975.

    Article  PubMed  CAS  Google Scholar 

  41. Press OW, Farr AG, Borroz I, et al.: Endocytosis and degradation of monoclonal antibodies targeting human B-cell malignancies. Cancer Res 49:4906, 1989.

    PubMed  CAS  Google Scholar 

  42. Press OW, Howell-Clark J, Anderson SK: Retention of B-cell specific monoclonal antibodies by human lymphoma cells. Blood 83:1390, 1994.

    PubMed  CAS  Google Scholar 

  43. Press OW, DeSantes K, Anderson SK, et al.: Inhibition of catabolism of radiolabeled antibodies by tumor cells using lysosomotropic amines and carboxylic ionophores. Cancer Res 50:1243, 1990.

    PubMed  CAS  Google Scholar 

  44. Zimmer AM, Kaplan EH, Kazikiewicz J, et al.: Pharmacokinetics of 1-131 T101 monoclonal antibody in patients with chronic lymphocytic leukemia. Antibody Immunoconju Radio-pharma 1:291, 1988.

    Google Scholar 

  45. Naruki Y, Carrasquillo JA, Reynolds JC, et al.: Differential cellular catabolism of In-111, Y-90, and I-125 radiolabeled T101 anti-CD5 monoclonal antibody. Nuclear Med Biol 17:201, 1990.

    CAS  Google Scholar 

  46. Carrasquillo JA, Mulshine JL, Bunn PAJ, et al.: Indium-111 T101 monoclonal antibody is superior to iodine-131 T101 in imaging of cutaneous T-cell lymphoma. J Nuclear Med 28:281, 1987.

    CAS  Google Scholar 

  47. Lenhard RE, Order SE, Spunberg JJ, et al.: Isotopic immunoglobulin: A new systemic therapy for advanced Hodgkin’s disease. J Clin Oncol 3:1296, 1985.

    PubMed  Google Scholar 

  48. DeNardo GL, DeNardo SJ, O’Grady LF, et al.: Fractionated radioimmunotherapy of B-cell malignancies with I-131-Lym-1. Cancer Res 50(Suppl):1014s, 1990.

    CAS  Google Scholar 

  49. Parker BA, Vassos AB, Halpern SF, et al.: Radioimmunotherapy of human B-cell lymphoma with Y-90-conjugated anti-idiotype monoclonal antibody. Cancer Res 50:1022s, 1990.

    PubMed  CAS  Google Scholar 

  50. Czuczman MS, Straus DJ, Divgi CR, et al.: Phase I dose-escalation trial of iodine 131-labeled monoclonal antibody OKB7 in patients with non-Hodgkin’s lymphoma. J Clin Oncol 11:2021, 1993.

    PubMed  CAS  Google Scholar 

  51. Scheinberg DA, Straus DJ, Yeh SD, et al.: A phase I toxicity, pharmacology, and dosimetry trial of monoclonal antibody OKB7 in patients with non-Hodgkin’s lymphoma: Effects of tumor burden and antigen expression. J Clin Oncol 8:792, 1990.

    PubMed  CAS  Google Scholar 

  52. Goldenberg DM, Horowitz JA, Sharkey RM, et al.: Targeting, dosimetry and radioimmunotherapy of B-cell lymphomas with iodine-131 labeled LL2 monoclonal antibody. J Clin Oncol 9:548, 1991.

    PubMed  CAS  Google Scholar 

  53. Kaminski MS, Fig LM, Zasadny KR, et al.: Imaging, dosimetry, and radioimmunotherapy with iodine 131-labeled anti-CD37 antibody in B cell lymphoma. J Clin Oncol 10:1696, 1992.

    PubMed  CAS  Google Scholar 

  54. Waldmann TA, Pastan IH, Gansow OA, et al.: The multichain interleukin-2 receptor: A target for immunotherapy. Ann Intern Med 116:148, 1992.

    PubMed  CAS  Google Scholar 

  55. Rosen ST, Zimmer AM, Goldman-Leikin R, et al.: Progress in the treatment of cutaneous T cell lymphomas with radiolabeled monoclonal antibodies. Nuclear Med Biol 16:667, 1989.

    CAS  Google Scholar 

  56. Zimmer AM, Rosen ST, Spies SM, et al.: Radioimmunotherapy of patients with cutaneous T-cell lymphoma using an iodine-131-labeled monoclonal antibody: analysis of retreatment following plasmapheresis. J Nuclear Med 29:124, 1988.

    Google Scholar 

  57. Kaminski MS, Zasadny KR, Milik AW, et al.: Updated results of a phase I trial of 131-1-anti-Bl (anti-CD20) radioimmunotherapy (RIT) for refractory B-cell lymphomas. Blood 82:332, 1993.

    Google Scholar 

  58. Blumenthal RD, Sharkey RM, Snyder DJ, et al.: Reduction of radioantibody-induced myelotoxicity in hamsters by recombinant interleukin-1. Cancer Res 48:5403, 1988.

    PubMed  CAS  Google Scholar 

  59. Bierman PJ, Vose JM, Leichner PK, et al.: Yttrium-90-labeled antiferritin followed by high-dose chemotherapy and autologous bone marrow transplantation for poor-prognosis Hodgkin’s disease. J Clin Oncol 11:698, 1993.

    PubMed  CAS  Google Scholar 

  60. Eary JF, Press OW, Badger CC, et al.: Imaging and treatment of B-cell lymphoma. J Nuclear Med 31:1257, 1990.

    CAS  Google Scholar 

  61. Fisher DR, Badger CC, Breitz H, et al.: Internal radiation dosimetry for clinical testing of radiolabeled monoclonal antibodies. Antibody Immunoconj Radiopharm 4:655, 1991.

    Google Scholar 

  62. Fujimori K, Covell DG, Fletcher, JE et al.: A modeling analysis of monoclonal antibody percolation through tumors: A binding-site barrier. J Nuclear Med 31:1191, 1990.

    CAS  Google Scholar 

  63. Curti BD, Urba WJ, Alvord WG, et al.: Interstitial pressure of subcutaneous nodules in melanoma and lymphoma patients: Changes during treatment. Cancer Res 53:2204, 1993.

    PubMed  CAS  Google Scholar 

  64. Ali SA, Warren SD, Richter KY, et al.: Improving the tumor retention of radioiodinated antibody: Aryl carbohydrate adducts. Cancer Res 50(Suppl):783s, 1990.

    PubMed  CAS  Google Scholar 

  65. Zalutsky MR, Noska MA, Colapinto EV, et al.: Enhanced tumor localization and in vivo stability of a monoclonal antibody radioiodinated using N-succinimidyl 3-(tri-n-butylstannyl)benzoate. Cancer Res 49:5543, 1989.

    PubMed  CAS  Google Scholar 

  66. Breitz HB, Weiden PL, Vanderheyden J, et al.: Clinical experience with rhenium-186-labeled monoclonal antibodies for radioimmunotherapy: Results of phase I trials. J Nuclear Med 33:1099, 1992.

    CAS  Google Scholar 

  67. LoBuglio AF, Wheeler RH, Trang J, et al.: Mouse/human chimeric monoclonal antibody in man: Kinetics and immune response. Proc Natl Acad Sci USA 86:4220, 1989.

    Article  PubMed  CAS  Google Scholar 

  68. Hale G, Clark MR, Marcus R, et al.: Remission induction in non-Hodgkin lymphoma with reshaped human monoclonal antibody Campath-1H. Lancet 1394:1394–1399, 1988.

    Article  Google Scholar 

Download references

Authors
  1. Ollie W. Press
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Janet F. Eary
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Frederick R. Appelbaum
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Irwin D. Bernstein
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

    C. Dean Buckner  & R. A. Clift  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1995 Springer Science+Business Media New York

About this chapter

Cite this chapter

Press, O.W., Eary, J.F., Appelbaum, F.R., Bernstein, I.D. (1995). Myeloablative Radiolabeled Antibody Therapy with Autologous Bone marrow Transplantation for Relapsed B Cell Lymphomas. In: Buckner, C.D., Clift, R.A. (eds) Technical and Biological Components of Marrow Transplantation. Cancer Treatment and Research, vol 76. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2013-9_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-2013-9_13

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5832-9

  • Online ISBN: 978-1-4615-2013-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation