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


Authors: Burke, J. M. ; Caron, P. C.; Papadopoulos, E. B.; Divgi, C. R.; Sgouros, G.; Panageas, K. S.; Finn, R. D.; Larson, S. M.; O'Reilly, R. J.; Scheinberg, D. A.; Jurcic, J. G.
Article Title: Cytoreduction with iodine-131-anti-CD33 antibodies before bone marrow transplantation for advanced myeloid leukemias
Abstract: 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 (122-437mCi) 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.
Keywords: adolescent; adult; cancer survival; child; clinical article; controlled study; human tissue; treatment outcome; child, preschool; middle aged; survival analysis; leukemia; transplantation, homologous; acute granulocytic leukemia; human cell; busulfan; hydroxyurea; clinical trial; cancer recurrence; cytotoxic agent; advanced cancer; ascites; dose response; drug safety; drug targeting; radiation dose; methotrexate; controlled clinical trial; infection; liver toxicity; bone marrow; bone marrow suppression; spleen; protein targeting; antineoplastic combined chemotherapy protocols; cyclophosphamide; allogenic bone marrow transplantation; chronic myeloid leukemia; time; radiation dosage; monoclonal antibodies; abdominal pain; dyspnea; fever; flushing; imaging system; standard; survival time; liver; antibodies, monoclonal; myelodysplastic syndrome; rigor; donor; feasibility study; recombinant antibody; iodine 131; drug distribution; isotope labeling; drug combination; tissue distribution; iodine radioisotopes; dosimetry; paracetamol; immunogenicity; hepatomegaly; leukemia cell; leukemia, myeloid; graft versus host reaction; transplantation conditioning; nausea and vomiting; methylprednisolone; hyperbilirubinemia; drug blood level; antigens, cd; radioisotope; drug half life; mesna; immunoglobulin g2a; immunosuppressive treatment; body burden; radioimmunotherapy; cyclosporin a; bone marrow transplantation; hemorrhagic cystitis; glycoprotein; cancer cell destruction; drug delivery system; urticaria; immunosuppressive agent; relative; cd33 antigen; thymocyte antibody; leukemia remission; antigens, differentiation, myelomonocytic; diphenhydramine; interstitial pneumonia; chronic myeloid; weight gain; myeloid leukemia; frequency analysis; allopurinol; immunoconjugates; vein occlusion; scintillation camera; radiation absorption; monoclonal antibody m 195; body weight disorder; humans; human; male; female; priority journal; article; acute myelocytic leukemia; lugol; potassium perchlorate
Journal Title: Bone Marrow Transplantation
Volume: 32
Issue: 6
ISSN: 0268-3369
Publisher: Nature Publishing Group  
Date Published: 2003-09-01
Start Page: 549
End Page: 556
Language: English
DOI: 10.1038/sj.bmt.1704201
PUBMED: 12953125
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 12 September 2014 -- Source: Scopus
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MSK Authors
  1. George Sgouros
    143 Sgouros
  2. Chaitanya Divgi
    139 Divgi
  3. John Burke
    4 Burke
  4. Ronald D Finn
    268 Finn
  5. Joseph G Jurcic
    130 Jurcic
  6. Katherine S Panageas
    332 Panageas
  7. Steven M Larson
    812 Larson
  8. Philip C Caron
    39 Caron
  9. Richard O'Reilly
    508 O'Reilly