Ringdén Olle
Division of Clinical Immunology, Karolinska Institutet, Karolinska University, Hospital, Huddinge, SE-141 86 Stockholm, Sweden.
Adv Cancer Res. 2007;97:25-60. doi: 10.1016/S0065-230X(06)97002-X.
During the past three decades, allogeneic stem cell transplantation (ASCT) has developed from being an experimental therapy in patients with endstage leukemia into a well-established therapy in patients with a range of disorders of the immunohematopoietic system. Graft-versus-host disease (GVHD), acute or chronic, attacking host tissue is a major threat. However, donor immunocompetent T cells have a potent graft-versus-leukemia effect. A combination of calcineurin inhibitors and methotrexate is the standard therapy to prevent GVHD. Modulation of the immunosuppressive regimen may induce mild acute and mild chronic GVHD, reduce the risk of relapse, and improve long-term survival. Natural killer cells also play a role in this context. Killer cell immunoglobulin-like receptor incompatibility between recipient and donor may reduce the risk of relapse in patients with myeloid leukemia. Relapse of leukemia is a major cause of death after ASCT. Minimal residual disease and recipient leukemia lineage-specific chimerism are sensitive techniques for early detection of leukemic relapse. Donor lymphocyte infusions can enhance the antitumor effect, especially for patients with molecular relapse. The allogeneic graft-versus-cancer effect has been demonstrated in patients with metastatic breast, renal, colorectal, ovarian, prostatic, and pancreatic carcinoma. Mesenchymal stem cells have immunomodulatory properties and may be used for immunomodulation of GVHD and tissue repair. All things considered, the future looks promising for ASCT.
在过去三十年中，异基因干细胞移植（ASCT）已从一种针对晚期白血病患者的实验性疗法发展成为针对一系列免疫造血系统疾病患者的成熟疗法。移植物抗宿主病（GVHD），无论是急性还是慢性，侵袭宿主组织都是一个主要威胁。然而，供体具有免疫活性的T细胞具有强大的抗白血病作用。钙调神经磷酸酶抑制剂和甲氨蝶呤联合使用是预防GVHD的标准疗法。调整免疫抑制方案可能会诱发轻度急性和轻度慢性GVHD，降低复发风险，并提高长期生存率。自然杀伤细胞在这方面也发挥作用。受体与供体之间的杀伤细胞免疫球蛋白样受体不相容性可能会降低髓系白血病患者的复发风险。白血病复发是ASCT后死亡的主要原因。微小残留病和受体白血病谱系特异性嵌合体是早期检测白血病复发的敏感技术。供体淋巴细胞输注可以增强抗肿瘤作用，特别是对于分子复发的患者。异基因移植物抗肿瘤作用已在转移性乳腺癌、肾癌、结直肠癌、卵巢癌、前列腺癌和胰腺癌患者中得到证实。间充质干细胞具有免疫调节特性，可用于GVHD的免疫调节和组织修复。综上所述，ASCT的未来前景广阔。
