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Blood, 1 March 2006, Vol. 107, No. 5, pp. 2184-2191. Prepublished online as a Blood First Edition Paper on October 27, 2005; DOI 10.1182/blood-2005-06-2317. This Article Full Text (PDF) All Versions of this Article: 2005-06-2317v1 107/5/2184    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Pagel, J. M Articles by Matthews, D. C Search for Related Content PubMed PubMed Citation Articles by Pagel, J. M Articles by Matthews, D. C Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 16, 2005 Accepted October 12, 2005 131I-ANTI-CD45 antibody plus busulfan and cyclophosphamide before allogeneic hematopoietic cell transplantation for treatment of acute myeloid leukemia in first remission John M Pagel*, Frederick R Appelbaum, Janet F Eary, Joseph Rajendran, Darrell R Fisher, Ted Gooley, Katherine Ruffner, Eneida Nemecek, Eileen Sickle, Larry Durack, Jeanette Carreras, Mary M Horowitz, Oliver W Press, Ajay K Gopal, Paul J Martin, Irwin D Bernstein, and Dana C Matthews Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Pediatrics, University of Washington, Seattle, WA, USA Department of Radiology, University of Washington, Seattle, WA, USA Pacific Northwest National Laboratory, Richland, WA, USA Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USA Medical College of Wisconsin, Milwaukee, WI, USA * Corresponding author; email: jpagel{at}fhcrc.org. In an attempt to improve outcomes for patients with acute myeloid leukemia (AML) after allogeneic hematopoietic cell transplantation (HCT), we conducted a Phase I/II study in which targeted irradiation delivered by 131I-anti-CD45 antibody was combined with targeted busulfan (BU; area-under-curve, 600-900 ng/ml) and cyclophosphamide (CY; 120 mg/kg). Fifty-two of 59 patients (88%) receiving a trace 131I-labeled dose of 0.5 mg/kg anti-CD45 murine antibody had higher estimated absorbed radiation in bone marrow and spleen than in any other organ. Forty-six patients were treated with 102-298 mCi 131I delivering an estimated 5.3-19 (mean 11.3) Gy to marrow, 17-72 (mean 29.7) Gy to spleen, and 3.5 Gy (n=4) to 5.25 Gy (n=42) to the liver. The estimated 3-year non-relapse mortality and disease-free survival (DFS) were 21% and 61%, respectively. These results were compared to those from 509 similar International Bone Marrow Transplant Registry patients transplanted using BU/CY alone. After adjusting for differences in age and cytogenetics-risk, the hazard of mortality among all antibody-treated patients was 0.65 times that of the Registry patients (95% CI 0.39-1.08; p=.09). The addition of targeted hematopoietic irradiation to conventional BU/CY is feasible and well tolerated, and Phase II results are sufficiently encouraging to warrant further study. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. J. Green, J. M. Pagel, E. R. Nemecek, Y. Lin, A. Kenoyer, A. Pantelias, D. K. Hamlin, D. S. Wilbur, D. R. Fisher, J. G. Rajendran, et al. Pretargeting CD45 enhances the selective delivery of radiation to hematolymphoid tissues in nonhuman primates Blood, August 6, 2009; 114(6): 1226 - 1235. [Abstract] [Full Text] [PDF] A. K. Gopal, J. M. Pagel, J. R. Fromm, S. Wilbur, and O. W. Press 131I anti-CD45 radioimmunotherapy effectively targets and treats T-cell non-Hodgkin lymphoma Blood, June 4, 2009; 113(23): 5905 - 5910. [Abstract] [Full Text] [PDF] H. Nakamae, D. S. Wilbur, D. K. Hamlin, M. S. Thakar, E. B. Santos, D. R. Fisher, A. L. Kenoyer, J. M. Pagel, O. W. Press, R. Storb, et al. Biodistributions, Myelosuppression, and Toxicities in Mice Treated with an Anti-CD45 Antibody Labeled with the {alpha}-Emitting Radionuclides Bismuth-213 or Astatine-211 Cancer Res., March 15, 2009; 69(6): 2408 - 2415. [Abstract] [Full Text] [PDF] P. Kletting, D. Bunjes, S. N. Reske, and G. Glatting Improving Anti-CD45 Antibody Radioimmunotherapy Using a Physiologically Based Pharmacokinetic Model J. Nucl. Med., February 1, 2009; 50(2): 296 - 302. [Abstract] [Full Text] [PDF] J. M. Pagel, D. C. Matthews, A. Kenoyer, D. K. Hamlin, D. S. Wilbur, D. R. Fisher, A. K. Gopal, Y. Lin, L. Saganic, F. R. Appelbaum, et al. Pretargeted Radioimmunotherapy Using Anti-CD45 Monoclonal Antibodies to Deliver Radiation to Murine Hematolymphoid Tissues and Human Myeloid Leukemia Cancer Res., January 1, 2009; 69(1): 185 - 192. [Abstract] [Full Text] [PDF] A. K. Gopal, O. W. Press, S. M. Wilbur, D. G. Maloney, and J. M. Pagel Rituximab blocks binding of radiolabeled anti-CD20 antibodies (Ab) but not radiolabeled anti-CD45 Ab Blood, August 1, 2008; 112(3): 830 - 835. [Abstract] [Full Text] [PDF] R. B. Walter, K. M. Boyle, F. R. Appelbaum, I. D. Bernstein, and J. M. Pagel Simultaneously targeting CD45 significantly increases cytotoxicity of the anti-CD33 immunoconjugate, gemtuzumab ozogamicin, against acute myeloid leukemia (AML) cells and improves survival of mice bearing human AML xenografts Blood, May 1, 2008; 111(9): 4813 - 4816. [Abstract] [Full Text] [PDF] J. M. Pagel, N. Hedin, L. Drouet, B. L. Wood, A. Pantelias, Y. Lin, D. K. Hamlin, D. S. Wilbur, A. K. Gopal, D. Green, et al. Eradication of disseminated leukemia in a syngeneic murine leukemia model using pretargeted anti-CD45 radioimmunotherapy Blood, February 15, 2008; 111(4): 2261 - 2268. [Abstract] [Full Text] [PDF] G. Glatting, M. Muller, B. Koop, K. Hohl, C. Friesen, B. Neumaier, E. Berrie, P. Bird, G. Hale, N. M. Blumstein, et al. Anti-CD45 Monoclonal Antibody YAML568: A Promising Radioimmunoconjugate for Targeted Therapy of Acute Leukemia J. Nucl. Med., August 1, 2006; 47(8): 1335 - 1341. [Abstract] [Full Text] [PDF] Y. Lin, J. M. Pagel, D. Axworthy, A. Pantelias, N. Hedin, and O. W. Press A Genetically Engineered Anti-CD45 Single-Chain Antibody-Streptavidin Fusion Protein for Pretargeted Radioimmunotherapy of Hematologic Malignancies. Cancer Res., April 1, 2006; 66(7): 3884 - 3892. [Abstract] [Full Text] [PDF] C. A. Schiffer Clinical Issues in the Management of Patients with Myelodysplasia Hematology, January 1, 2006; 2006(1): 205 - 210. [Abstract] [Full Text] [PDF]

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