Ballen K K, Becker P S, Stewart F M, Quesenberry P J
University of Massachusetts Cancer Center, Worcester, USA.
Semin Oncol. 2000 Oct;27(5):512-23.
Hematologic malignancies affect more than 80,000 patients in the United States each year. Some patients with lymphoma and leukemia are cured with conventional chemotherapy treatments. For others, autologous or allogeneic bone marrow transplantation may be the best therapeutic option. This chapter will explore novel therapies for the hematologic malignancies, using the stem cell as a target. We review work in the murine model looking at (1) the phenotype of the engrafting cells, (2) stem cell competition and host stem cells, (3) allochimerism with low-dose total body irradiation, and (4) the tolerance approach with costimulator blockade. Human data, including stem cell migration, adhesion receptor expression, and manipulations for gene therapy, are reviewed. The NOD/scid mouse model serves as a bridge between the basic bench work and human clinical trials, and we discuss applications related to umbilical cord blood and gene therapy, as well as discuss the inherent variability of this system. Finally, we address unique clinical applications in gene therapy, high-dose cell transplants, minimal myeloablation, and cellular immune therapy as approaches to treatment of for patients with hematologic malignancies.
在美国，每年有超过8万名患者受到血液系统恶性肿瘤的影响。一些淋巴瘤和白血病患者通过传统化疗得以治愈。而对于其他患者，自体或异基因骨髓移植可能是最佳治疗选择。本章将探讨以干细胞为靶点的血液系统恶性肿瘤的新型疗法。我们回顾了在小鼠模型中的研究工作，内容包括：（1）植入细胞的表型；（2）干细胞竞争与宿主干细胞；（3）低剂量全身照射后的异源嵌合现象；（4）共刺激阻断的耐受性方法。同时也回顾了人类相关数据，包括干细胞迁移、黏附受体表达以及基因治疗操作。NOD/scid小鼠模型是基础研究与人类临床试验之间的桥梁，我们将讨论其在脐带血和基因治疗方面的应用，以及该系统固有的变异性。最后，我们将阐述基因治疗、高剂量细胞移植、最小化骨髓消融和细胞免疫治疗等独特的临床应用，作为治疗血液系统恶性肿瘤患者的方法。
