In:
Blood, American Society of Hematology, Vol. 94, No. 4 ( 1999-08-15), p. 1237-1247
Abstract:
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/kg131I-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 mCi131I 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.
Type of Medium:
Online Resource
ISSN:
1528-0020
,
0006-4971
DOI:
10.1182/blood.V94.4.1237.416k34_1237_1247
Language:
English
Publisher:
American Society of Hematology
Publication Date:
1999
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
Permalink
