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Conditioning Regimens

Cytoreduction with iodine-131-anti-CD33 antibodies before bone marrow transplantation for advanced myeloid leukemias

Bone Marrow Transplantation volume 32, pages 549–556 (2003)Cite this article

Summary:

The monoclonal antibodies M195 and HuM195 target CD33, a glycoprotein found on myeloid leukemia cells. When labeled with iodine-131 (131I), these antibodies can eliminate large disease burdens and produce prolonged myelosuppression. We studied whether 131I-labeled M195 and HuM195 could be combined safely with busulfan and cyclophosphamide (BuCy) as conditioning for allogeneic BMT. A total of 31 patients with relapsed/refractory acute myeloloid leukemia (AML) (n=16), accelerated/myeloblastic chronic myeloid leukemia (CML) (n=14), or advanced myelodysplastic syndrome (n=1) received 131I-M195 or 131I-HuM195 (122–437 mCi) plus busulfan (16 mg/kg) and cyclophosphamide (90–120 mg/kg) followed by infusion of related-donor bone marrow (27 first BMT; four second BMT). Hyperbilirubinemia was the most common extramedullary toxicity, occurring in 69% of patients during the first 28 days after BMT. Gamma camera imaging showed targeting of the radioisotope to the bone marrow, liver, and spleen, with absorbed radiation doses to the marrow of 272–1470 cGy. The median survival was 4.9 months (range 0.3–90+ months). Three patients with relapsed AML remain in complete remission 59+, 87+, and 90+ months following bone marrow transplantation (BMT). These studies show the feasibility of adding CD33-targeted radioimmunotherapy to a standard BMT preparative regimen; however, randomized trials will be needed to prove a benefit to intensified conditioning with radioimmunotherapy.

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Authors and Affiliations

  1. Departments of Medicine, Radiology, Medical Physics, and Biostatistics, Memorial Sloan-Kettering Cancer Center and the Weill Medical College of Cornell University, New York, NY, USA

    J M Burke, P C Caron, E B Papadopoulos, C R Divgi, G Sgouros, K S Panageas, R D Finn, S M Larson, R J O'Reilly, D A Scheinberg & J G Jurcic

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  1. J M Burke
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Correspondence to J G Jurcic.

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This work was supported by National Institutes of Health Grants PO1 CA33049 and RO1 CA55349.

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Burke, J., Caron, P., Papadopoulos, E. et al. Cytoreduction with iodine-131-anti-CD33 antibodies before bone marrow transplantation for advanced myeloid leukemias. Bone Marrow Transplant 32, 549–556 (2003). https://doi.org/10.1038/sj.bmt.1704201

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