131I-anti-CD45 antibody plus busulfan and cyclophosphamide before allogeneic hematopoietic cell transplantation for treatment of acute myeloid leukemia in first remission - PubMed (original) (raw)
Clinical Trial
. 2006 Mar 1;107(5):2184-91.
doi: 10.1182/blood-2005-06-2317. Epub 2005 Oct 27.
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, Dana C Matthews
Affiliations
- PMID: 16254140
- PMCID: PMC1895719
- DOI: 10.1182/blood-2005-06-2317
Clinical Trial
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 et al. Blood. 2006.
Abstract
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.
Figures
Figure 1.
131I–anti-CD45 antibody localization. Anterior images of pelvis demonstrating localization of 131I-BC8 antibody in a patient with AML in remission 0 hours (A) and 41 hours (B) after infusion of trace-labeled antibody.
Figure 2.
Estimates of the probability of DFS, NRM, and relapse among all patients who received a therapeutic dose of 131I-BC8 antibody, followed by BU/CY.
Figure 3.
Estimates of the probability of DFS, NRM, and relapse among patients with intermediate-risk cytogenetics who received a therapeutic dose of 131I-BC8 antibody, followed by BU/CY.
Figure 4.
Estimates of the probability of DFS, NRM, and relapse among patients with unfavorable cytogenetics who received a therapeutic dose of 131I-BC8 antibody, followed by BU/CY.
References
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