Dose-escalation trial of M195 labeled with iodine 131 for cytoreduction and marrow ablation in relapsed or refractory myeloid leukemias Journal Article

Authors: Schwartz, M. A.; Lovett, D. R.; Redner, A.; Finn, R. D.; Graham, M. C.; Divgi, C. R.; Dantis, L.; Gee, T. S.; Andreeff, M.; Old, L. J.; Larson, S. M.; Scheinberg, D. A.
Article Title: Dose-escalation trial of M195 labeled with iodine 131 for cytoreduction and marrow ablation in relapsed or refractory myeloid leukemias
Abstract: Purpose: Mouse monoclonal antibody (mAb) M195 (anti-CD33) is reactive with most myeloid leukemia cells, monocytes, and hematopoietic progenitors, but not with other hematopoietic cells or stem cells nor with nonhematopoietic human tissues. A therapeutic dose-escalation study of M195 labeled with iodine 131 was conducted in patients with relapsed or refractory myeloid leukemias. Methods: Twenty-four patients (16 relapsed or refractory acute myeloid leukemias, five blastic myelodysplastic syndromes [MDS], two chemotherapy-related secondary leukemias, and one blastic chronic myelogenous leukemia [CML]), including seven who had failed to respond to prior bone marrow transplantation (BMT), received from 50 mCi/m2 to 210 mCi/m2 of 131I-M195 in divided doses. Results: In 22 patients, whole-body gamma-imaging demonstrated marked uptake of antibody into all areas of bone marrow. Twenty-three patients (96%) demonstrated decreases in peripheral-blood cell counts, with decreased percentage of bone marrow blasts seen in 83% of cases. Eighty-nine percent of bone marrow biopsies examined quantitatively demonstrated sub-stantial decreases in the number of blasts, with greater than 99% of blasts killed in some patients. The two cases that failed to demonstrate leukemic cytoreduction occurred in the first two dose levels. For 131I doses of 135 mCi/m2 or greater, pancytopenia was profound and lasted for at least 12 days. Eight patients had sufficient marrow cytoreduction to proceed to BMT. Three of these achieved marrow remission, one of 6+, and one of 9 months' duration. Two patients in blastic phase temporarily reverted to their original myelodysplastic states. Thirty-seven percent of assessable patients developed human anti-mouse antibody (HAMA). In two patients with HAMA who were re-treated, plasma 131I-M195 levels could not be maintained and no therapeutic effect resulted. Significant nonhematologic toxicity (hepatic) was seen in one patient and the maximum-tolerated dose (MTD) was not reached. Conclusion: These data suggest that safe leukemic cytoreduction can be achieved with 131I-M195 even in multiply relapsed or chemotherapy-refractory leukemias. This agent may be useful as part of a preparative regimen for BMT. © 1993 by American Society of Clinical Oncology.
Keywords: adolescent; adult; child; clinical article; treatment outcome; aged; child, preschool; cancer recurrence; dose response; drug efficacy; flow cytometry; animal; mice; cancer immunotherapy; bone marrow; recurrence; bone pain; antineoplastic activity; drug effect; monoclonal antibody; fever; antibodies, monoclonal; drug uptake; isotope labeling; iodine radioisotopes; bone marrow biopsy; leukemia, myeloid; target cell; radioimmunotherapy; blast cell; middle age; myeloid leukemia; monoclonal antibody m 195; human; male; female; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.
Journal Title: Journal of Clinical Oncology
Volume: 11
Issue: 2
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 1993-02-01
Start Page: 294
End Page: 303
Language: English
DOI: 10.1200/jco.1993.11.2.294
PUBMED: 8426207
PROVIDER: scopus
Notes: Article -- Export Date: 1 March 2019 -- Source: Scopus
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MSK Authors
  1. Chaitanya Divgi
    128 Divgi
  2. Ronald D Finn
    255 Finn
  3. Steven M Larson
    784 Larson
  4. Lloyd J Old
    386 Old
  5. Martin C Graham
    31 Graham
  6. Lucy A Dantis
    8 Dantis