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Development of a marrow transplant regimen for acute leukemia using
targeted hematopoietic irradiation delivered by 131I-labeled anti-CD45
antibody, combined with cyclophosphamide and total body irradiation
DC Matthews, FR Appelbaum, JF Eary, DR Fisher, LD Durack, SA Bush, TE Hui, PJ Martin, D Mitchell and OW Press
Division of Clinical Research, Fred Hutchinson Cancer Research Center,
Seattle 98104.
In an attempt to decrease the relapse rate after bone marrow
transplantation (BMT) for advanced acute leukemia, we initiated studies
using 131I-labeled anti-CD45 antibody (BC8) to deliver radiation
specifically to hematopoietic tissues, followed by a standard transplant
preparative regimen. Biodistribution studies were performed in 23 patients
using 0.5 mg/kg trace 131I-labeled BC8 antibody. The BC8 antibody was
cleared rapidly from plasma with an initial disappearance half-time of 1.5
+/- 0.2 hours, presumably reflecting rapid antigen- specific binding. The
mean radiation absorbed doses (cGy/mCi131I administered) were as follows:
marrow, 7.1 +/- 0.8; spleen, 10.8 +/- 1.4; liver, 2.7 +/- 0.2; lungs, 2.1
+/- 0.1; kidneys, 0.7 +/- 0.1; and total body, 0.4 +/- 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 retention of radionuclide in marrow. Twenty patients were
treated with a dose of 131I estimated to deliver 3.5 Gy (level 1) to 7 Gy
(level 3) to liver, with marrow doses of 4 to 30 Gy and spleen doses of 7
to 60 Gy, followed by 120 mg/kg cyclophosphamide (CY) and 12 Gy total body
irradiation (TBI). Nine of 13 patients with AML or refractory anemia with
excess blasts (RAEB) and two of seven with acute lymphocytic leukemia (ALL)
are alive disease-free at 8 to 41 months (median, 17 months) after BMT.
Toxicity has not been measurably greater than that of CY/TBI alone, and the
maximum tolerated dose has not been reached. This study demonstrates that
with the use of 131I-BC8 substantially greater doses of radiation can be
delivered to hematopoietic tissues as compared with liver, lung, or kidney,
which may improve the efficacy of marrow transplantation.
Volume 85,
Issue 4,
pp. 1122-1131,
02/15/1995
Copyright © 1995 by The American Society of Hematology
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