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Blood, Vol. 94 No. 4 (August 15), 1999:
pp. 1237-1247
Phase I Study of 131I-Anti-CD45 Antibody Plus
Cyclophosphamide and Total Body Irradiation for Advanced Acute Leukemia
and Myelodysplastic Syndrome
Dana C. Matthews,
Frederick R. Appelbaum,
Janet F. Eary,
Darrell
R. Fisher,
Lawrence D. Durack,
T. Edmond Hui,
Paul J. Martin,
David Mitchell,
Oliver W. Press,
Rainer Storb, and
Irwin D. Bernstein
From the Division of Clinical Research, Fred Hutchinson Cancer
Research Center, and the Departments of Pediatrics, Medicine and
Radiology, University of Washington, Seattle, WA; and Pacific Northwest
National Laboratories, Richland, WA.
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 120 mg/kg cyclophosphamide (CY) and 12 Gy total body
irradiation (TBI) followed by HLA-matched related allogeneic or
autologous transplant. Forty-four patients with advanced acute leukemia
or myelodysplasia received a biodistribution dose of 0.5 mg/kg
131I-BC8 (murine anti-CD45) antibody. The mean ± SEM
estimated radiation absorbed dose (centigray per
millicurie of 131I) delivered to bone marrow
and spleen was 6.5 ± 0.5 and 13.5 ± 1.3, respectively, with liver,
lung, kidney, and total body receiving lower amounts of 2.8 ± 0.2, 1.8 ± 0.1, 0.6 ± 0.04, and 0.4 ± 0.02, respectively. Thirty-seven
patients (84%) had favorable biodistribution of antibody,
with a higher estimated radiation absorbed dose to marrow and spleen
than to normal organs. Thirty-four patients received a therapeutic dose
of 131I-antibody labeled with 76 to 612 mCi
131I to deliver estimated radiation absorbed doses to liver
(normal organ receiving the highest dose) of 3.5 Gy (level 1) to 12.25 Gy (level 6) in addition to CY and TBI. The maximum tolerated dose was
level 5 (delivering 10.5 Gy to liver), with grade III/IV mucositis in 2 of 2 patients treated at level 6. Of 25 treated patients with acute
myeloid leukemia (AML)/myelodysplastic syndrome (MDS), 7 survive disease-free 15 to 89 months (median, 65 months) posttransplant. Of 9 treated patients with acute lymphoblastic leukemia
(ALL), 3 survive disease-free 19, 54, and 66 months
posttransplant. We conclude that 131I-anti-CD45 antibody
can safely deliver substantial supplemental doses of radiation to bone
marrow (~24 Gy) and spleen (~50 Gy) when combined with conventional
CY/TBI.
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