采用¹⁸⁸Re标记的抗CD66抗体进行清髓性放射免疫疗法，用于高危白血病患者干细胞移植前的预处理：生物分布、生物动力学及近期毒性反应

Myeloablative radioimmunotherapy with Re-188-anti-CD66-antibody for conditioning of high-risk leukemia patients prior to stem cell transplantation: biodistribution, biokinetics and immediate toxicities.

作者信息

Buchmann Inga, Bunjes Donald, Kotzerke Jörg, Martin Hans, Glatting Gerhard, Seitz Ulrike, Rattat Dirk, Buck Andreas, Döhner Hartmut, Reske Sven N

机构信息

Department of Nuclear Medicine, University Hospital, Ulm, Germany.

出版信息

Cancer Biother Radiopharm. 2002 Apr;17(2):151-63. doi: 10.1089/108497802753773775.

DOI:10.1089/108497802753773775

PMID:12030109

Abstract

BACKGROUND

Stem cell transplantation (SCT) is potentially curative for high-risk leukemia patients. Conditioning regimens affect relapse rate and treatment-related mortality. We evaluated biodistribution, radiation absorbed organ doses and immediate toxicities of myeloablative radioimmunotherapy with marrow selective 188rhenium (188Re)-labeled anti-CD66 monoclonal antibody (mAb).

METHODS

Fifty high-risk leukemia patients were treated 14 +/- 2 days prior to SCT. Dosimetric measurements were performed at 1.5, 3, 20, 26, and 44 hours after about 1 GBq of 188Re followed by radioimmunotherapy with about 10 GBq 188Re. Standard conditioning consisted of high-dose chemotherapy and 12 Gy total-body irradiation. Forty-six patients received allogenic, and four received autologous, stem cell grafts.

RESULTS

The mean radiation absorbed doses (in Gy) were: marrow, 13.9 +/- 4.6; liver, 5.7 +/- 2.7; spleen, 22.6 +/- 25.5; kidneys, 6.8 +/- 2.6; lungs, 0.8 +/- 0.7; total body, 1.4 +/- 0.3. The tumor-to-organ-ratios were 2.4 for liver, 0.6 for the spleen, 2.0 for the kidneys and 17.8 for the lungs. Type of leukemia did not affect radiation absorbed doses of marrow, lungs, kidneys and liver. Mean marrow dose of transplanted patients in complete remission was 1.37 +/- 0.43 Gy/GBq, compared with 1.34 +/- 0.29 Gy/GBq for patients with leukemic blast marrow infiltration of 5-25%. Immediate side effects were moderate. All patients showed primary engraftment. After a median follow-up of 11.0 +/- 7.4 months 28/50 patients (56%) are in ongoing complete remission. Nine patients (5%) have relapsed, seven (4%) of them have died. Another 13 patients (7%) died of treatment-related causes.

CONCLUSIONS

Due to its biodistribution, radiation absorbed organ doses, low toxicity and clinical data, myeloablative radioimmunotherapy with 188Re-labeled anti-CD66 mAb seems to be a promising method for improving standard conditioning of high-risk leukemia patients prior to SCT.

摘要

背景

干细胞移植（SCT）对高危白血病患者可能具有治愈作用。预处理方案会影响复发率和治疗相关死亡率。我们评估了用骨髓选择性188铼（188Re）标记的抗CD66单克隆抗体（mAb）进行清髓性放射免疫治疗的生物分布、辐射吸收器官剂量及即时毒性。

方法

50例高危白血病患者在SCT前14±2天接受治疗。在给予约1GBq 188Re后1.5、3、20、26和44小时进行剂量测定，随后用约10GBq 188Re进行放射免疫治疗。标准预处理包括大剂量化疗和12Gy全身照射。46例患者接受异基因干细胞移植，4例接受自体干细胞移植。

结果

平均辐射吸收剂量（单位：Gy）为：骨髓，13.9±4.6；肝脏，5.7±2.7；脾脏，22.6±25.5；肾脏，6.8±2.6；肺，0.8±0.7；全身，1.4±0.3。肿瘤与器官的比值分别为：肝脏2.4，脾脏0.6，肾脏2.0，肺17.8。白血病类型不影响骨髓、肺、肾脏和肝脏的辐射吸收剂量。完全缓解的移植患者的平均骨髓剂量为1.37±0.43Gy/GBq，而白血病原始细胞骨髓浸润率为5%-25%的患者为1.34±0.29Gy/GBq。即时副作用为中度。所有患者均实现初次植入。中位随访11.0±7.4个月后，50例患者中有28例（56%）持续完全缓解。9例患者（5%）复发，其中7例（4%）死亡。另有13例患者（7%）死于治疗相关原因。