|
|
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.
 Previous Article | Table of Contents | Next Article 
TRANSPLANTATION
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
From the Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA; the Departments of Pediatrics, Medicine, and Radiology, University of Washington, Seattle, WA; the Pacific Northwest National Laboratory, Richland, WA; and the Medical College of Wisconsin, Milwaukee, WI.
In an attempt to improve outcomes for patients with acute myeloid leukemia (AML) after allogeneic hematopoietic cell transplantation (HCT), we conducted a phase 1/2 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 (88%) of 59 patients 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 to 298 mCi (3774-11 026 MBq) 131I, delivering an estimated 5.3 to 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 nonrelapse mortality and disease-free survival (DFS) were 21% and 61%, respectively. These results were compared with those from 509 similar International Bone Marrow Transplant Registry patients who underwent transplantation 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 2 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:
|
|
|
|
 
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]
|
|
|
| |
