Phase I study of I-131-anti-CD45 antibody plus cyclophosphamide and total body irradiation for advanced acute leukemia and myelodysplastic syndrome

Delivery of targeted hematopoietic irradiation using radiolabeled monoclona l antibody may improve the outcome of marrow transplantation for advanced a cute leukemia by decreasing relapse without increasing toxicity. We conduct ed a phase 1 study that examined the biodistribution of I-131-labeled anti- CD45 antibody and determined the toxicity of escalating doses of targeted r adiation 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 myelodyspl asia received a biodistribution dose of 0.5 mg/kg I-131-BC8 (murine anti-CD Q5) antibody. The mean +/- SEM estimated radiation absorbed dose (centigray per millicurie of I-131) 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 biodistr ibution of antibody, with a higher estimated radiation absorbed dose to mar row and spleen than to normal organs. Thirty-four patients received a thera peutic dose of I-131-antibody labeled with 76 to 612 mCi I-131 to deliver e stimated radiation absorbed doses to liver (normal organ receiving the high est dose) of 3.5 Gy (level 1) to 12.25 Gy (level 6) in addition to CY and T BI, The maximum tolerated dose was level 5 (delivering 10.5 Gy to liver), w ith grade III/IV mucositis in 2 of 2 patients treated at level 6. Of 25 tre ated patients with acute myeloid leukemia (AML)/myelodysplastic syndrome (M DS), 7 survive disease-free 15 to 89 months (median, 65 months) posttranspl ant. Of 9 treated patients with acute lymphoblastic leukemia (ALL), 3 survi ve disease-free 19, 54, and 66 months posttransplant. We conclude that I-13 1-anti-CD45 antibody can safely deliver substantial supplemental doses of r adiation to bone marrow (similar to 24 Gy) and spleen (similar to 50 Gy) wh en combined with conventional CY/TBI. (C) 1999 by The American Society of H ematology.