Phase I study of 131I-anti-CD45 antibody plus cyclophosphamide and total body irradiation for advanced acute leukemia and myelodysplastic syndrome
Phase I study of 131I-anti-CD45 antibody plus cyclophosphamide and total body irradiation for advanced acute leukemia and myelodysplastic syndrome
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DOI：
10.1182/blood.v94.4.1237.416k34_1237_1247
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发表时间：
1999-08-15
期刊：
影响因子：
20.3
通讯作者：
Bernstein, ID
中科院分区：
文献类型：
--
作者：
Matthews, DC;Appelbaum, FR;Bernstein, ID
应用放射性标记单克隆抗体进行造血靶向照射治疗晚期急性白血病，可在不增加毒副反应的情况下减少复发，从而改善骨髓移植的疗效。我们进行了一项I期研究，检查了I-131标记的抗CD 45抗体的生物分布，并确定了递增剂量的靶向放射联合120 mg/kg环磷酰胺（CY）和12戈伊全身照射（TBI），随后进行HLA匹配的相关同种异体或自体移植的毒性。44例晚期急性白血病或骨髓增生异常患者接受了生物分布剂量为0.5 mg/kg的I-131-BC 8（鼠抗CDQ 5）抗体。平均+/- SEM估计辐射吸收剂量（每毫居里I-131厘戈瑞）分别为6.5 +/- 0.5和13.5 +/- 1.3，肝、肺、肾和全身接受的量较低，分别为2.8 +/- 0.2、1.8 +/- 0.1、0.6 +/- 0.04，和0.4 +/-0.02。37例患者（84%）的抗体生物分布良好，骨髓和脾脏的估计辐射吸收剂量高于正常器官。34名患者接受治疗剂量的I-131-抗体，标记76至612 mCi I-131，以向肝脏输送估计的辐射吸收剂量3.5戈伊（1级）~ 12.25戈伊（6级），最大耐受剂量为5级（向肝脏输送10.5戈伊），在6级治疗的2例患者中有2例出现III/IV级粘膜炎。在25例接受治疗的急性髓性白血病（AML）/骨髓增生异常综合征（MDS）患者中，7例在移植后15至89个月（中位数，65个月）无病生存。在9例接受治疗的急性淋巴细胞白血病（ALL）患者中，3例在移植后19、54和66个月无病生存。我们得出结论，当与常规CY/TBI组合时，I-131-抗-CD 45抗体可以安全地向骨髓（类似于24戈伊）和脾脏（类似于50戈伊）递送实质性补充剂量的辐射。(C)1999年，美国血液学会。
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 1 study that examined the biodistribution of I-131-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 I-131-BC8 (murine anti-CDQ5) 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 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 I-131-antibody labeled with 76 to 612 mCi I-131 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 I-131-anti-CD45 antibody can safely deliver substantial supplemental doses of radiation to bone marrow (similar to 24 Gy) and spleen (similar to 50 Gy) when combined with conventional CY/TBI. (C) 1999 by The American Society of Hematology.