131I-anti-CD45 antibody plus busulfan and cyclophosphamide before allogeneic hematopoietic cell transplantation for treatment of acute myeloid leukemia in first remission.
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.
Pagel
John M
JM
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
Appelbaum
Frederick R
FR
Eary
Janet F
JF
Rajendran
Joseph
J
Fisher
Darrell R
DR
Gooley
Ted
T
Ruffner
Katherine
K
Nemecek
Eneida
E
Sickle
Eileen
E
Durack
Larry
L
Carreras
Jeanette
J
Horowitz
Mary M
MM
Press
Oliver W
OW
Gopal
Ajay K
AK
Martin
Paul J
PJ
Bernstein
Irwin D
ID
Matthews
Dana C
DC
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
D000911:Antibodies, Monoclonal; D007456:Iodine Isotopes; D003520:Cyclophosphamide; D002066:Busulfan