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Conditioning Regimens

A dose escalation study of total body irradiation followed by high-dose etoposide and allogeneic blood stem cell transplantation for the treatment of advanced hematologic malignancies

Bone Marrow Transplantation volume 25, pages 807–813 (2000)Cite this article

Abstract

Since approximately 30% of leukemia patients relapse after allogeneic BMT using total body irradiation (TBI)-based preparative regimens, treatment intensity may be suboptimal. The killing of leukemia cells is proportional to the radiation absorbed dose. We studied the feasibility and toxicity of escalating the doses of fractionated TBI above our previous prescription of 13.5 Gy. Sixteen evaluable patients with advanced hematologic malignancies were treated with twice daily TBI using a high-energy source (18–24 MV). The first patient cohort (n = 11) received a total dose of 14.4 Gy in nine fractions, and the second cohort (n = 5) received doses escalated to 15.3 Gy. All patients received high-dose etoposide (60 mg/kg) and allogeneic stem cell transplantation following the TBI. All patients had HLA-identical sibling donors. The median times for neutrophil and platelet engraftment were 13.5 and 12 days, respectively, and did not differ between the two cohorts. All but one patient developed treatment-related grade 3 or 4 mucositis. There were three cases of grade 4 pulmonary toxicity and three cases of grade 4 hepatic toxicity among the 14.4 Gy cohort, and one case each of grade 4 pulmonary and hepatic toxicities among the 15.3 Gy cohort. In most cases comorbid conditions contributed to these toxicities. Two patients had significant GVHD of the GI tract. Six relapses occurred, five (45%) in the 14.4 Gy cohort and one (20%) in the 15.3 Gy cohort. The 100-day treatment-related mortality rates were 9% and 20% for the 14.4 Gy and 15.3 Gy cohorts, respectively, and the median survivals were 226 and 201 days, respectively. We conclude that TBI dose escalation above the previously used 13.5 Gy dose is feasible using a high-energy source and high-dose etoposide. Acute and chronic toxicities were primarily related to GVHD, infection and relapse rather than to TBI. Bone Marrow Transplantation (2000) 25, 807–813.

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References

  1. Thomas ED, Storb R, Clift A et al. Bone marrow transplantation New Engl J Med 1975 292: 832–843, 895–902

    Google Scholar 

  2. Thomas ED, Buckner CD, Banaji M et al. One hundred patients with acute leukemia treated by chemotherapy, total body irradiation (TBI) and allogeneic marrow transplantation Blood 1977 49: 511–533

    CAS  PubMed  Google Scholar 

  3. Forman SJ, Blume K, Thomas ED . Bone Marrow Transplantation, 1st edn Little Brown and Co: Baltimore 1994

    Google Scholar 

  4. 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: 1015–1020

    CAS  PubMed  Google Scholar 

  5. Blume KG, Kopecky KJ, Henslee-Downey JP et al. 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: a Southwest Oncology Group Study Blood 1993 81: 2187–2193

    CAS  PubMed  Google Scholar 

  6. Brown RA, Wolff SN, Fay JW et al. High-dose etoposide, cyclophosphamide, and total body irradiation with allogeneic bone marrow transplantation for patients with acute myeloid leukemia in untreated first relapse: a study by the North American Transplant Group Blood 1995 85: 1391–1395

    CAS  PubMed  Google Scholar 

  7. 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: 889–897

    Article  CAS  Google Scholar 

  8. McGlave PB, Arthur DC, Kim TH et al. Successful allogeneic bone marrow transplantation for patients in the accelerated phase of chronic granulocytic leukemia Lancet 1982 2: 625–627

    Article  CAS  Google Scholar 

  9. Michel G, Gluckman E, Blaise D et al. Improvement in outcome for children receiving allogeneic bone marrow transplantation in first remission for acute myeloid leukemia: a report from the Group d'Etude des Greffes de Moelle Osseuse J Clin Oncol 1992 10: 1865–1869

    Article  CAS  Google Scholar 

  10. Schmitz N, Gassmann W, Rister M et al. Fractionated total body irradiation and high-dose VP 16-213 followed by allogeneic bone marrow transplantation in advanced leukemias Blood 1988 72: 1567–1573

    CAS  PubMed  Google Scholar 

  11. Spitzer TR, Peters C, Ortlieb M et al. Etoposide in combination with cyclophosphamide and total body irradiation or busulfan as conditioning for marrow transplantation in adults and children Int J Radiat Oncol Biol Phys 1994 29: 39–44

    Article  CAS  Google Scholar 

  12. Spruce WE . Bone Marrow Transplantation. I. Use in neoplastic diseases (review) Am J Public Health 1983 5: 287–294

    Article  CAS  Google Scholar 

  13. Deeg HJ, Storb R, Longton G et al. Single dose or fractionated total body irradiation and autologous marrow transplantation in dogs: effects of exposure rate, fraction size and fractionation interval on acute and delayed toxicity Int J Radiat Oncol Biol Phys 1988 15: 647–653

    Article  CAS  Google Scholar 

  14. Deeg HJ, Storb R, Weiden PL et al. High-dose total body irradiation and autologous marrow reconstitution in dogs: dose-rate-related acute toxicity and fractionation-dependent long-term survival Radiat Res 1981 88: 385–391

    Article  CAS  Google Scholar 

  15. Hagenbeek A, Martens ACM . The effect of fractionated versus unfractionated total body irradiation on the growth of the BN acute myelocytic leukemia Int J Radiat Oncol Biol Phys 1981 7: 1075–1079

    Article  CAS  Google Scholar 

  16. Lichter AS, Tracy D, Lam WC et al. Total body irradiation in bone marrow transplantation: the influence of fractionation and delay of marrow infusion Int J Radiat Oncol Biol Phys 1980 6: 301–309

    Article  CAS  Google Scholar 

  17. Deeg HJ, Sullivan KM, Buckner CD et al. Marrow transplantation for acute nonlymphoblastic leukemia in first remission: toxicity and long-term follow-up of patients conditioned with single dose or fractionated total body irradiation Bone Marrow Transplant 1986 1: 151–157

    CAS  PubMed  Google Scholar 

  18. Dinsmore R, Kirkpatrick D, Flomenberg N et al. Allogeneic bone marrow transplantation for patients with acute lymphoblastic leukemia Blood 1983 62: 381–388

    CAS  PubMed  Google Scholar 

  19. Thomas ED, Clift RA, Hersman J 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

    Article  CAS  Google Scholar 

  20. Cosset JM, Socie G, Dubray B et al. Single dose versus fractionated total body irradiation before bone marrow transplantation: radiobiological and clinical considerations Int J Radiat Oncol Biol Phys 1994 30: 477–492

    Article  CAS  Google Scholar 

  21. Petersen FB, Deeg HJ, Buckner CD et al. Marrow transplantation following escalating doses of fractionated total body irradiation and cyclophosphamide-A phase I trial Int J Radiat Oncol Biol Phys 1992 23: 1027–1032

    Article  CAS  Google Scholar 

  22. Clift RA, Buckner CD, Appelbaum FR et al. Allogeneic marrow transplantation in patients with chronic myeloid leukemia in the chronic phase: a randomized trial of two irradiation regimens Blood 1991 77: 1660–1665

    CAS  PubMed  Google Scholar 

  23. Bradley J, Reft C, Goldman S et al. High-energy total body irradiation as preparation for bone marrow transplantation in leukemia patients: treatment technique and related complications Int J Radiat Oncol Biol Phys 1998 40: 391–396

    Article  CAS  Google Scholar 

  24. Sibley GS, Mundt AJ, Goldman S et al. Patterns of failure following total body irradiation and bone marrow transplantation Int J Radiat Oncol Biol Phys 1995 32: 1127–1135

    Article  CAS  Google Scholar 

  25. Cancer Therapy and Evaluation Program . Common toxicity critera. In: NCI Division of Cancer Treatment Guidelines for Reporting of Adverse Drug Reactions National Cancer Institute: Bethesda, MD 1989

  26. Quast U . Total body irradiation. Review of treatment techniques in Europe Radiother Oncol 1987 9: 91–106

    Article  CAS  Google Scholar 

  27. Shank B . Techniques of magna field irradiation Int J Radiat Oncol Biol Phys 1983 9: 1925–1931

    Article  CAS  Google Scholar 

  28. Shank B . Total body irradiation for marrow or stem cell transplantation Cancer Invest 1998 16: 397–404

    Article  CAS  Google Scholar 

  29. Lindsley K, Deeg HJ . Total body irradiation for marrow or stem cell transplantation Cancer Invest 1998 16: 424–425

    Article  CAS  Google Scholar 

  30. Clift RA, Buckner CD, Bianco J et al. Marrow transplantation in patients with acute myeloid leukemia Leukemia 1992 6: (Suppl. 2) 104–109

    PubMed  Google Scholar 

  31. Clift RA, Buckner CD, Applebaum FR et al. 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

    CAS  PubMed  Google Scholar 

  32. Dopfer R, Henz G, Bender-Gotze C et al. Allogeneic bone marrow transplantation for childhoood acute lymphoblastic leukemia in second remission after intensive primary and relapse therapy according to the BFM and CoAll protocols. Results of the German Cooperative Study Blood 1991 78: 2780–2784

    CAS  Google Scholar 

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Acknowledgements

This research was supported in part by grants from the National Institutes of Health (CA-14599, CA-70937 and CA-58506), Bethesda, Maryland. We thank Beth Weseman, RN and Collen Tazic, RN for their expert nursing and Melissa Ellifson for data management.

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Authors and Affiliations

  1. Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, IL, USA

    RM Sobecks, CK Daugherty, GF Laport, ND Wagner & RA Larson

  2. Department of Radiation and Cellular Oncology, and the Cancer Research Center, The University of Chicago, Chicago, IL, USA

    DE Hallahan

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  1. RM Sobecks
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Sobecks, R., Daugherty, C., Hallahan, D. et al. A dose escalation study of total body irradiation followed by high-dose etoposide and allogeneic blood stem cell transplantation for the treatment of advanced hematologic malignancies. Bone Marrow Transplant 25, 807–813 (2000). https://doi.org/10.1038/sj.bmt.1702230

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