scholarly journals Radiolabeled anti-CD45 monoclonal antibodies target lymphohematopoietic tissue in the macaque

Blood ◽  
1991 ◽  
Vol 78 (7) ◽  
pp. 1864-1874 ◽  
Author(s):  
DC Matthews ◽  
FR Appelbaum ◽  
JF Eary ◽  
TE Hui ◽  
DR Fisher ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Monoclonal Antibodies ◽  
Lymph Nodes ◽  
Marrow Transplantation ◽  
Absorbed Dose ◽  
Hematologic Malignancies ◽  
Macaca Nemestrina ◽  
Improve Treatment ◽  
Antibody Uptake ◽  
Relative Specificity

Abstract Despite bone marrow transplantation, many patients with advanced leukemia subsequently relapse. If an additional increment of radiation could be delivered to lymphohematopoietic tissues with relative specificity, the relapse rate may decrease without a marked increase in toxicity. We have examined the biodistribution of two 131I-labeled monoclonal antibodies reactive with the CD45 antigen in Macaca nemestrina. Three animals received 0.5 mg/kg BC8, an IgG1 of low avidity (6 x 10(7) L/mol). Three received 0.5 mg/kg AC8, an IgG2a of moderate avidity (5 x 10(8) L/mol), and two received 4.5 mg/kg AC8. Estimates of radiation absorbed dose demonstrated that these antibodies could deliver up to five times more radiation to lymph nodes, and up to 2.6 times more to bone marrow, than to lung or liver. The higher avidity AC8 antibody at 0.5 mg/kg was cleared more rapidly from blood and resulted in lower antibody uptake in lymph nodes than did BC8 at 0.5 mg/kg. Increasing the dose of AC8 to 4.5 mg/kg resulted in slower blood clearance and higher lymph node uptake. These studies suggest that radiolabeled anti-CD45 antibodies can deliver radiation with relative specificity to lymphohematopoietic tissues. This approach, in combination with marrow transplantation, may improve treatment of hematologic malignancies.

scholarly journals Radiolabeled anti-CD45 monoclonal antibodies target lymphohematopoietic tissue in the macaque

Blood ◽  
1991 ◽  
Vol 78 (7) ◽  
pp. 1864-1874 ◽  
Author(s):  
DC Matthews ◽  
FR Appelbaum ◽  
JF Eary ◽  
TE Hui ◽  
DR Fisher ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Monoclonal Antibodies ◽  
Lymph Nodes ◽  
Marrow Transplantation ◽  
Absorbed Dose ◽  
Hematologic Malignancies ◽  
Macaca Nemestrina ◽  
Improve Treatment ◽  
Antibody Uptake ◽  
Relative Specificity

Despite bone marrow transplantation, many patients with advanced leukemia subsequently relapse. If an additional increment of radiation could be delivered to lymphohematopoietic tissues with relative specificity, the relapse rate may decrease without a marked increase in toxicity. We have examined the biodistribution of two 131I-labeled monoclonal antibodies reactive with the CD45 antigen in Macaca nemestrina. Three animals received 0.5 mg/kg BC8, an IgG1 of low avidity (6 x 10(7) L/mol). Three received 0.5 mg/kg AC8, an IgG2a of moderate avidity (5 x 10(8) L/mol), and two received 4.5 mg/kg AC8. Estimates of radiation absorbed dose demonstrated that these antibodies could deliver up to five times more radiation to lymph nodes, and up to 2.6 times more to bone marrow, than to lung or liver. The higher avidity AC8 antibody at 0.5 mg/kg was cleared more rapidly from blood and resulted in lower antibody uptake in lymph nodes than did BC8 at 0.5 mg/kg. Increasing the dose of AC8 to 4.5 mg/kg resulted in slower blood clearance and higher lymph node uptake. These studies suggest that radiolabeled anti-CD45 antibodies can deliver radiation with relative specificity to lymphohematopoietic tissues. This approach, in combination with marrow transplantation, may improve treatment of hematologic malignancies.

scholarly journals 52Fe for additional marrow ablation before bone marrow transplantation

Blood ◽  
1993 ◽  
Vol 81 (12) ◽  
pp. 3435-3439 ◽  
Author(s):  
A Ferrant ◽  
M Cogneau ◽  
N Leners ◽  
F Jamar ◽  
P Martiat ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Conditioning Regimen ◽  
Absorbed Dose ◽  
Hematologic Malignancies ◽  
Whole Body ◽  
Median Percentage ◽  
Preparative Regimen

Abstract The effectiveness of bone marrow transplantation (BMT) for malignant blood diseases remains limited by the inability of the preparative regimen to eliminate the disease without causing toxicity to normal organs. We have used 52Fe to deliver radiotherapy selectively to the BM. Fourteen patients with hematologic malignancies received 52Fe before a conventional BMT conditioning regimen. The median 52Fe dose was 58 mCi (range, 32 to 85 mCi). As evaluated by quantitative scanning, the median percentage of 52Fe taken up by the BM was 82% (range, 36% to 90%). This resulted in a median radiation-absorbed dose to the BM of 632 rad (range, 151 to 1,144 rad). The median uptake of 52Fe by the liver was 18% (range, 10% to 64%) and the median radiation-absorbed dose to the liver was 239 rad (range, 82 to 526 rad). The median whole body radiation-absorbed dose was 46 rad (range, 22 to 68 rad). No untoward effects were noted after the injections of 52Fe. The patients recovered hematopoiesis without toxicity in excess of that expected with conventional conditioning alone. The median follow-up was 8 months and three patients have relapsed. 52Fe should provide a way to boost the radiation dose to marrow-based diseases before marrow transplantation without increasing toxicity.

52Fe for additional marrow ablation before bone marrow transplantation

Blood ◽  
1993 ◽  
Vol 81 (12) ◽  
pp. 3435-3439
Author(s):  
A Ferrant ◽  
M Cogneau ◽  
N Leners ◽  
F Jamar ◽  
P Martiat ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Conditioning Regimen ◽  
Absorbed Dose ◽  
Hematologic Malignancies ◽  
Whole Body ◽  
Median Percentage ◽  
Preparative Regimen

The effectiveness of bone marrow transplantation (BMT) for malignant blood diseases remains limited by the inability of the preparative regimen to eliminate the disease without causing toxicity to normal organs. We have used 52Fe to deliver radiotherapy selectively to the BM. Fourteen patients with hematologic malignancies received 52Fe before a conventional BMT conditioning regimen. The median 52Fe dose was 58 mCi (range, 32 to 85 mCi). As evaluated by quantitative scanning, the median percentage of 52Fe taken up by the BM was 82% (range, 36% to 90%). This resulted in a median radiation-absorbed dose to the BM of 632 rad (range, 151 to 1,144 rad). The median uptake of 52Fe by the liver was 18% (range, 10% to 64%) and the median radiation-absorbed dose to the liver was 239 rad (range, 82 to 526 rad). The median whole body radiation-absorbed dose was 46 rad (range, 22 to 68 rad). No untoward effects were noted after the injections of 52Fe. The patients recovered hematopoiesis without toxicity in excess of that expected with conventional conditioning alone. The median follow-up was 8 months and three patients have relapsed. 52Fe should provide a way to boost the radiation dose to marrow-based diseases before marrow transplantation without increasing toxicity.

Monoclonal Antibodies in Bone Marrow Transplantation

1983 ◽  
pp. 121-128
Author(s):  
G. JANOSSY ◽  
A.V. HOFFBRAND ◽  
H.G. PRENTICE ◽  
G. FRANCIS ◽  
N. TIDMAN ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Monoclonal Antibodies ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation

scholarly journals Naturally occurring anticoagulants and bone marrow transplantation: plasma protein C predicts the development of venocclusive disease of the liver

Blood ◽  
1993 ◽  
Vol 81 (12) ◽  
pp. 3458-3462 ◽  
Author(s):  
EM Faioni ◽  
A Krachmalnicoff ◽  
SI Bearman ◽  
AB Federici ◽  
A Decarli ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Protein C ◽  
Antithrombin Iii ◽  
Function Analysis ◽  
Predictive Marker ◽  
Protein S ◽  
Hematologic Malignancies ◽  
Naturally Occurring

Abstract Venocclusive disease (VOD) of the liver is the major dose-limiting complication of pretransplant regimens for bone marrow transplantation. Recent reports from different groups point to the involvement of the hemostatic mechanism in the development of VOD. We measured the naturally occurring anticoagulants protein C, antithrombin III, and protein S in 45 patients undergoing bone marrow transplantation for hematologic malignancies before cytoreductive therapy and after transplant. The aim of this prospective study was both to evaluate the status of the naturally occurring anticoagulant pathway in patients who develop VOD compared with patients who do not, and to find a predictive marker of VOD. In transplant patients, protein C decreased from before cytoreductive therapy to posttransplant, whereas protein S and antithrombin III did not. In a multivariate analysis, protein C was the only variable that could independently discriminate between VOD and non- VOD patients at all times. Discriminant function analysis established that low protein C levels before cytoreductive therapy predicted the occurrence of VOD with good sensitivity and specificity.

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