Reske S N, Bunjes D, Buchmann I, Seitz U, Glatting G, Neumaier B, Kotzerke J, Buck A, Martin H, Döhner H, Bergmann L
Abteilung Nuklearmedizin, Universitätsklinikum Ulm, Germany.
Eur J Nucl Med. 2001 Jul;28(7):807-15. doi: 10.1007/s002590100544.
Disease recurrence following stem cell transplantation (SCT) remains a major problem. Despite the sensitivity of leukaemias to chemotherapy and irradiation, conventional conditioning before SCT is limited by significant organ toxicity. Targeted irradiation of bone marrow and spleen by radioimmunotherapy may provide considerable dose escalation, with limited toxicity to non-target organs. In this study, 27 patients with high-risk or relapsing leukaemia were treated with rhenium-188-labelled CD66a,b,c,e radioimmunoconjugates (188Re-mAb) specific for normal bone marrow in addition to conventional conditioning with high-dose chemotherapy and 12 Gy total body irradiation prior to SCT. A mean activity of 10.2+/-2.1 (range 6.9-15.8) GBq 188Re-mAb was administered intravenously. Acute side-effects were assessed according to the CTC classification and patient outcome was determined. Mean radiation doses (Gy; range in parentheses) to relevant organs and whole body were as follows: 13.1 (6.5-22) to bone marrow, 11.6 (1.7-31.1) to spleen, 5.0 (2.0-11.7) to liver, 7.0 (2.3-11.6) to kidneys, 0.7 (0.3-1.3) to lungs and 1.4 (0.8-2.1) to the whole body. Stem cells engrafted in all patients within 9-18 days post SCT. Acute organ toxicity of grade II or less was observed. During follow-up for 25.4+/-5.3 (range 18-34) months, 4/27 (15%) patients died from relapse, and 9/27 (33%) from transplantation-related complications. Fourteen patients (52%) are still alive and in ongoing complete clinical remission. Radioimmunotherapy with the bone marrow-seeking 188Re-labelled CD66 mAb can double the dose to bone marrow and spleen without undue extramedullary acute organ toxicity, when given in addition to high-dose chemotherapy and 12 Gy TBI before allogeneic SCT. This intensified conditioning regimen may reduce the relapse rate of high-risk leukaemia.
干细胞移植（SCT）后的疾病复发仍然是一个主要问题。尽管白血病对化疗和放疗敏感，但SCT前的传统预处理受到显著器官毒性的限制。放射免疫疗法对骨髓和脾脏进行靶向照射可能会使剂量大幅增加，而对非靶器官的毒性有限。在本研究中，27例高危或复发白血病患者在SCT前除接受大剂量化疗和12 Gy全身照射的传统预处理外，还接受了针对正常骨髓的铼-188标记的CD66a、b、c、e放射免疫缀合物（188Re-单克隆抗体）治疗。静脉注射188Re-单克隆抗体的平均活度为10.2±2.1（范围6.9 - 15.8）GBq。根据CTC分类评估急性副作用并确定患者预后。相关器官和全身的平均辐射剂量（Gy；括号内为范围）如下：骨髓13.1（6.5 - 22）、脾脏11.6（1.7 - 31.1）、肝脏5.0（2.0 - 11.7）、肾脏7.0（2.3 - 11.6）、肺0.7（0.3 - 1.3）、全身1.4（0.8 - 2.1）。所有患者的干细胞在SCT后9 - 18天内植入。观察到二级或以下的急性器官毒性。在25.4±5.3（范围18 - 34）个月的随访期间，27例患者中有4例（15%）死于复发，9例（33%）死于移植相关并发症。14例患者（52%）仍然存活且处于持续完全临床缓解状态。在异基因SCT前，除大剂量化疗和12 Gy全身照射外，使用靶向骨髓的188Re标记的CD66单克隆抗体进行放射免疫疗法可使骨髓和脾脏的剂量增加一倍，而不会产生过度的髓外急性器官毒性。这种强化预处理方案可能会降低高危白血病的复发率。
