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

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.

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Figures

Figure 1.

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.

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.

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.

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

    1. Ringden O, Labopin M, Tura S, et al. A comparison of busulphan versus total body irradiation combined with cyclophosphamide as conditioning for autograft or allograft bone marrow transplantation in patients with acute leukaemia: Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Br J Haematol. 1996;93: 637-645. - PubMed
    1. Gale RP, Horowitz MM, Weiner RS, et al. Impact of cytogenetic abnormalities on outcome of bone marrow transplants in acute myelogenous leukemia in first remission. Bone Marrow Transplant. 1995;16: 203-208. - PubMed
    1. Ferrant A, Labopin M, Frassoni F, et al. Karyotype in acute myeloblastic leukemia: prognostic significance for bone marrow transplantation in first remission: a European Group for Blood and Marrow Transplantation study: Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Blood. 1997;90: 2931-2938. - PubMed
    1. Grimwade D, Walker H, Oliver F, et al. The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial: The Medical Research Council Adult and Children's Leukaemia Working Parties. Blood. 1998;92: 2322-2333. - PubMed
    1. Harousseau JL, Cahn JY, Pignon B, et al. Comparison of autologous bone marrow transplantation and intensive chemotherapy as postremission therapy in adult acute myeloid leukemia: The Groupe Ouest Est Leucemies Aigues Myeloblastiques (GOELAM). Blood. 1997;90: 2978-2986. - PubMed

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