Development of a Marrow Transplant Regimen for Acute Leukemia Using Targeted Hematopoietic Irradiation Delivered by I3lI-Labeled Anti-CD45 Antibody, Combined With Cyclophosphamide and Total Body Irradiation
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چکیده
In an attempt t o decrease the relapse rate after bone marrow transplantation (BMT) for advanced acute leukemia, we initiated studies using '3'1-labeled anti-CD45 antibody (BC81 to deliver radiation specifically t o hematopoietic tissues, followed by a standard transplant preparative regimen. Biodistribution studies were performed in 23 patients using 0.5 mg/kg trace '3'1-labeled BC8 antibody. The BC8 antibody was cleared rapidly from plasma with an initial disappearance half-time of 1.5 f 0.2 hours, presumably reflecting rapid antigen-specific binding. The mean radiation absorbed doses (cGy/mCi l3lI administered) were as follows: marrow, 7.1 +0.8; spleen, 10.8 f 1.4; liver, 2.7 f 0.2; lungs, 2.1 C 0.1; kidneys, 0.7 f 0.1; and total body, 0.4 f 0.03. Patients with acute myelogenous leukemia (AML) in relapse had a higher marrow dose (11.4 cGy/mCi) than those in remission (5.2 cGy/mCi; P = .001) because of higher uptake and longer
منابع مشابه
Marrow ablative and immunosuppressive effects of 131I-anti-CD45 antibody in congenic and H2-mismatched murine transplant models.
Targeted hematopoietic irradiation delivered by 131I-anti-CD45 antibody has been combined with conventional marrow transplant preparative regimens in an effort to decrease relapse. Before increasing the proportion of therapy delivered by radiolabeled antibody, the myeloablative and immunosuppressive effects of such low dose rate irradiation must be quantitated. We have examined the ability of 1...
متن کاملCLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Phase I Study of 131I-Anti-CD45 Antibody Plus Cyclophosphamide and Total Body Irradiation for Advanced Acute Leukemia and Myelodysplastic Syndrome
Delivery of targeted hematopoietic irradiation using radiolabeled monoclonal antibody may improve the outcome of marrow transplantation for advanced acute leukemia by decreasing relapse without increasing toxicity. We conducted a phase I study that examined the biodistribution of 131I-labeled anti-CD45 antibody and determined the toxicity of escalating doses of targeted radiation combined with ...
متن کاملCLINICAL TRIALS AND OBSERVATIONS Allogeneic hematopoietic cell transplantation after conditioning with 131I–anti-CD45 antibody plus fludarabine and low-dose total body irradiation for elderly patients with advanced acute myeloid leukemia or high-risk myelodysplastic syndrome
We conducted a study to estimate the maximum tolerated dose (MTD) of 131I– anti-CD45 antibody (Ab; BC8) that can be combined with a standard reduced-intensity conditioning regimen before allogeneic hematopoietic cell transplantation. Fiftyeight patients older than 50 years with advanced acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) were treated with 131I-BC8 Ab and fl...
متن کاملAllogeneic hematopoietic cell transplantation after conditioning with 131I-anti-CD45 antibody plus fludarabine and low-dose total body irradiation for elderly patients with advanced acute myeloid leukemia or high-risk myelodysplastic syndrome.
We conducted a study to estimate the maximum tolerated dose (MTD) of (131)I-anti-CD45 antibody (Ab; BC8) that can be combined with a standard reduced-intensity conditioning regimen before allogeneic hematopoietic cell transplantation. Fifty-eight patients older than 50 years with advanced acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) were treated with (131)I-BC8 Ab an...
متن کاملImmunosuppressive effects of (131)I-anti-CD45 antibody in unsensitized and donor antigen-presensitized H2-matched, minor antigen-mismatched murine transplant models.
Iodine-131-labeled anti-CD45 antibody has been added to conventional hematopoietic stem cell transplant preparative regimens to deliver targeted radiation to hematopoietic tissues, with the goal of decreasing relapse rates without increasing toxicity. However, higher radiation doses could be delivered to leukemia cells by antibody if the systemic therapy were decreased or eliminated. To examine...
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تاریخ انتشار 2002