title: Dose-escalation trial of M195 labeled with iodine 131 for cytoreduction and marrow ablation in relapsed or refractory myeloid leukemias.
abstract: OBJECTIVE
  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 substantial 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Leukemia Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
authors.forename: M A
authors.initials: MA
authors.lastname: Schwartz
authors.forename: D R
authors.initials: DR
authors.lastname: Lovett
authors.forename: A
authors.initials: A
authors.lastname: Redner
authors.forename: R D
authors.initials: RD
authors.lastname: Finn
authors.forename: M C
authors.initials: MC
authors.lastname: Graham
authors.forename: C R
authors.initials: CR
authors.lastname: Divgi
authors.forename: L
authors.initials: L
authors.lastname: Dantis
authors.forename: T S
authors.initials: TS
authors.lastname: Gee
authors.forename: M
authors.initials: M
authors.lastname: Andreeff
authors.forename: L J
authors.initials: LJ
authors.lastname: Old
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001853:Bone Marrow / Q000528:radiation effects; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D007951:Leukemia, Myeloid / Q000532:radiotherapy*; D008297:Male; D051379:Mice; D008875:Middle Aged; D016499:Radioimmunotherapy / Q000009:adverse effects; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes