Cytoreduction with iodine-131-anti-CD33 antibodies before bone marrow transplantation for advanced myeloid leukemias.
The monoclonal antibodies M195 and HuM195 target CD33, a glycoprotein found on myeloid leukemia cells. When labeled with iodine-131 ((131)I), these antibodies can eliminate large disease burdens and produce prolonged myelosuppression. We studied whether (131)I-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 (131)I-M195 or (131)I-HuM195 (122-437 mCi) 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.
Burke
J M
JM
Department of Medicine, Memorial Sloan-Kettering Cancer Center and the Weill Medical College of Cornell University, New York, NY, USA.
Caron
P C
PC
Papadopoulos
E B
EB
Divgi
C R
CR
Sgouros
G
G
Panageas
K S
KS
Finn
R D
RD
Larson
S M
SM
O'Reilly
R J
RJ
Scheinberg
D A
DA
Jurcic
J G
JG
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000379:methods* / Q000401:mortality; D002066:Busulfan / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000493:pharmacokinetics / Q000627:therapeutic use; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use; D007951:Leukemia, Myeloid / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011829:Radiation Dosage; D063268:Sialic Acid Binding Ig-like Lectin 3; D016019:Survival Analysis; D014018:Tissue Distribution; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D018796:Immunoconjugates; D007457:Iodine Radioisotopes; D063268:Sialic Acid Binding Ig-like Lectin 3; C101579:monoclonal antibody M195; D003520:Cyclophosphamide; D002066:Busulfan