Rhenium 188-labeled anti-CD66 (a, b, c, e) monoclonal antibody to intensify the conditioning regimen prior to stem cell transplantation for patients with high-risk acute myeloid leukemia or myelodysplastic syndrome: results of a phase I-II study.
The conditioning regimen prior to stem cell transplantation in 36 patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) was intensified by treating patients with a rhenium 188-labeled anti-CD66 monoclonal antibody. Dosimetry was performed prior to therapy, and a favorable dosimetry was observed in all cases. Radioimmunotherapy with the labeled antibody provided a mean of 15.3 Gy of additional radiation to the marrow; the kidney was the normal organ receiving the highest dose of supplemental radiation (mean 7.4 Gy). Radioimmunotherapy was followed by standard full-dose conditioning with total body irradiation (12 Gy) or busulfan and high-dose cyclophosphamide with or without thiotepa. Patients subsequently received a T-cell-depleted allogeneic graft from a HLA-identical family donor (n = 15) or an alternative donor (n = 17). In 4 patients without an allogeneic donor, an unmanipulated autologous graft was used. Infusion-related toxicity due to the labeled antibody was minimal, and no increase in treatment-related mortality due to the radioimmunoconjugate was observed. Day +30 and day +100 mortalities were 3% and 6%, respectively, and after a median follow-up of 18 months treatment-related mortality was 22%. Late renal toxicity was observed in 17% of patients. The relapse rate of 15 patients undergoing transplantation in first CR (complete remission) or second CR was 20%; 21 patients not in remission at the time of transplantation had a 30% relapse rate. (Blood. 2001;98:565-572)
Bunjes
D
D
Department of Haematology/Oncology, Ulm University Hospital, Robert-Koch-Strasse 8, 89091 Ulm, Germany. donald.bunjes@medizin.uni-ulm.de
Buchmann
I
I
Duncker
C
C
Seitz
U
U
Kotzerke
J
J
Wiesneth
M
M
Dohr
D
D
Stefanic
M
M
Buck
A
A
Harsdorf
S V
SV
Glatting
G
G
Grimminger
W
W
Karakas
T
T
Munzert
G
G
Döhner
H
H
Bergmann
L
L
Reske
S N
SN
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology*; D000943:Antigens, Differentiation / Q000276:immunology*; D015815:Cell Adhesion Molecules; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D007951:Leukemia, Myeloid / Q000150:complications / Q000175:diagnosis* / Q000628:therapy; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000175:diagnosis* / Q000628:therapy; D016499:Radioimmunotherapy / Q000009:adverse effects / Q000379:methods* / Q000592:standards; D011868:Radioisotopes; D012211:Rhenium; D012307:Risk Factors; D013601:T-Lymphocytes; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D011868:Radioisotopes; D012211:Rhenium