Mulroney C M, Glück S, Ho A D
University of California, San Diego Cancer Center 92103-8421.
Semin Oncol. 1994 Dec;21(6 Suppl 15):24-7.
High-dose chemotherapy and autologous bone marrow transplantation are an effective combination for treating a number of malignant disorders. Clinical trials have demonstrated a potential role for this regimen in the management of acute leukemia and non-Hodgkin's lymphoma. Autologous bone marrow transplantation continues to be limited by high relapse rates, as compared with allogeneic bone marrow transplantation. Two factors are thought to account for this observation. First, autologous transplants lack the immunologic "graft-versus-host" advantage of allogeneic transplants. Second, autologous grafts have the possibility of tumor cell contamination. Methods to reduce tumor cell contamination in autografts include exposure to chemical agents or monoclonal antibodies; long-term marrow cultures; and immunologic manipulation, either with immunomagnetic devices or antibody/complement combinations. Photodynamic therapy (PDT) with porfimer sodium (Photofrin; manufactured by Lederle Parenterals, Carolina, Puerto Rico, under license from Quadra Logic Technologies, Inc, Vancouver, British Columbia, Canada) or benzoporphyrin derivative (BPD verteporfin; BPD-MA; BPD-Quadra Logic Technologies, Inc, Vancouver, British Columbia, Canada) may be an effective means of purging bone marrow. The ability of malignant cells to selectively accumulate photosensitizing agents may account for efficacy of PDT in bone marrow purging. The efficacy of porfimer sodium and BPD has been evaluated in cell lines known to express multidrug resistance (MDR), and the results compared with corresponding MDR-negative cell lines. Multidrug resistance-positive cell lines appear relatively resistant to BPD; porfimer sodium remains active. The reason for the differential effect of MDR positivity on the cytotoxicity of porfimer sodium and BPD is unclear, but is believed to be related to the larger size of the porfimer sodium molecule. Clinical trials evaluating PDT in bone marrow transplantation are under way.
大剂量化疗和自体骨髓移植是治疗多种恶性疾病的有效组合。临床试验已证明该方案在急性白血病和非霍奇金淋巴瘤的治疗中具有潜在作用。与异基因骨髓移植相比，自体骨髓移植的复发率仍然很高，这限制了其应用。有两个因素被认为可以解释这一现象。首先，自体移植缺乏异基因移植的免疫“移植物抗宿主”优势。其次，自体移植物有可能被肿瘤细胞污染。减少自体移植物中肿瘤细胞污染的方法包括接触化学试剂或单克隆抗体；长期骨髓培养；以及使用免疫磁珠装置或抗体/补体组合进行免疫操作。使用卟吩姆钠（光卟啉；由Lederle Parenterals公司根据加拿大不列颠哥伦比亚省温哥华Quadra Logic Technologies公司的许可在波多黎各卡罗来纳生产）或苯并卟啉衍生物（维替泊芬；BPD-MA；Quadra Logic Technologies公司，加拿大不列颠哥伦比亚省温哥华）进行光动力疗法（PDT）可能是清除骨髓的有效方法。恶性细胞选择性积累光敏剂的能力可能是PDT在骨髓清除中发挥作用的原因。已在已知表达多药耐药性（MDR）的细胞系中评估了卟吩姆钠和BPD的疗效，并将结果与相应的MDR阴性细胞系进行了比较。多药耐药阳性细胞系对BPD相对耐药；卟吩姆钠仍然有效。MDR阳性对卟吩姆钠和BPD细胞毒性产生差异效应的原因尚不清楚，但认为与卟吩姆钠分子较大有关。评估PDT在骨髓移植中应用的临床试验正在进行中。
