Myeloablative radioimmunotherapy with Re-188-anti-CD66-antibody for conditioning of high-risk leukemia patients prior to stem cell transplantation: biodistribution, biokinetics and immediate toxicities.
BACKGROUND
Stem cell transplantation (SCT) is potentially curative for high-risk leukemia patients. Conditioning regimens affect relapse rate and treatment-related mortality. We evaluated biodistribution, radiation absorbed organ doses and immediate toxicities of myeloablative radioimmunotherapy with marrow selective 188rhenium (188Re)-labeled anti-CD66 monoclonal antibody (mAb).


METHODS
Fifty high-risk leukemia patients were treated 14 +/- 2 days prior to SCT. Dosimetric measurements were performed at 1.5, 3, 20, 26, and 44 hours after about 1 GBq of 188Re followed by radioimmunotherapy with about 10 GBq 188Re. Standard conditioning consisted of high-dose chemotherapy and 12 Gy total-body irradiation. Forty-six patients received allogenic, and four received autologous, stem cell grafts.


RESULTS
The mean radiation absorbed doses (in Gy) were: marrow, 13.9 +/- 4.6; liver, 5.7 +/- 2.7; spleen, 22.6 +/- 25.5; kidneys, 6.8 +/- 2.6; lungs, 0.8 +/- 0.7; total body, 1.4 +/- 0.3. The tumor-to-organ-ratios were 2.4 for liver, 0.6 for the spleen, 2.0 for the kidneys and 17.8 for the lungs. Type of leukemia did not affect radiation absorbed doses of marrow, lungs, kidneys and liver. Mean marrow dose of transplanted patients in complete remission was 1.37 +/- 0.43 Gy/GBq, compared with 1.34 +/- 0.29 Gy/GBq for patients with leukemic blast marrow infiltration of 5-25%. Immediate side effects were moderate. All patients showed primary engraftment. After a median follow-up of 11.0 +/- 7.4 months 28/50 patients (56%) are in ongoing complete remission. Nine patients (5%) have relapsed, seven (4%) of them have died. Another 13 patients (7%) died of treatment-related causes.


CONCLUSIONS
Due to its biodistribution, radiation absorbed organ doses, low toxicity and clinical data, myeloablative radioimmunotherapy with 188Re-labeled anti-CD66 mAb seems to be a promising method for improving standard conditioning of high-risk leukemia patients prior to SCT.
Buchmann
Inga
I
Department of Nuclear Medicine, University Hospital, Ulm, Germany. inga.buchmann@medizin.uni-ulm.de
Bunjes
Donald
D
Kotzerke
Jörg
J
Martin
Hans
H
Glatting
Gerhard
G
Seitz
Ulrike
U
Rattat
Dirk
D
Buck
Andreas
A
Döhner
Hartmut
H
Reske
Sven N
SN
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015703:Antigens, CD / Q000276:immunology*; D000943:Antigens, Differentiation / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology / Q000528:radiation effects; D015815:Cell Adhesion Molecules; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007938:Leukemia / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000628:therapy*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000000981:diagnostic imaging / Q000378:metabolism / Q000628:therapy; D007951:Leukemia, Myeloid / Q000000981:diagnostic imaging / Q000378:metabolism / Q000628:therapy; D008099:Liver / Q000378:metabolism / Q000528:radiation effects; D008168:Lung / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000000981:diagnostic imaging / Q000378:metabolism / Q000628:therapy; D011829:Radiation Dosage; D016499:Radioimmunotherapy; D011868:Radioisotopes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D011877:Radionuclide Imaging; D012211:Rhenium / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015996:Survival Rate; D014018:Tissue Distribution; D019172:Transplantation Conditioning
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D011868:Radioisotopes; D012211:Rhenium