title: 131I-anti-CD45 antibody plus busulfan and cyclophosphamide before allogeneic hematopoietic cell transplantation for treatment of acute myeloid leukemia in first remission.
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.
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center D5-380, 1100 Fairview Ave N, PO Box 19024, Seattle, WA 98109, USA. jpagel@fhcrc.org
authors.forename: John M
authors.initials: JM
authors.lastname: Pagel
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: Janet F
authors.initials: JF
authors.lastname: Eary
authors.forename: Joseph
authors.initials: J
authors.lastname: Rajendran
authors.forename: Darrell R
authors.initials: DR
authors.lastname: Fisher
authors.forename: Ted
authors.initials: T
authors.lastname: Gooley
authors.forename: Katherine
authors.initials: K
authors.lastname: Ruffner
authors.forename: Eneida
authors.initials: E
authors.lastname: Nemecek
authors.forename: Eileen
authors.initials: E
authors.lastname: Sickle
authors.forename: Larry
authors.initials: L
authors.lastname: Durack
authors.forename: Jeanette
authors.initials: J
authors.lastname: Carreras
authors.forename: Mary M
authors.initials: MM
authors.lastname: Horowitz
authors.forename: Oliver W
authors.initials: OW
authors.lastname: Press
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Gopal
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Martin
authors.forename: Irwin D
authors.initials: ID
authors.lastname: Bernstein
authors.forename: Dana C
authors.initials: DC
authors.lastname: Matthews
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001853:Bone Marrow / Q000473:pathology; D002066:Busulfan / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007456:Iodine Isotopes / Q000008:administration & dosage; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011878:Radiotherapy / Q000379:methods; D012074:Remission Induction; D012307:Risk Factors; D013154:Spleen / Q000473:pathology; D014184:Transplantation, Homologous
chemical_list: D000911:Antibodies, Monoclonal; D007456:Iodine Isotopes; D003520:Cyclophosphamide; D002066:Busulfan