Nonmyeloablative allogeneic stem cell transplantation: early promise and limitations.
Nonmyeloablative allogeneic stem cell transplantation: early promise and limitations.
复制标题
非清髓性同种异体干细胞移植：早期前景和局限性。
DOI：
10.1634/theoncologist.5-6-487
复制
发表时间：
2000
期刊：
影响因子：
--
通讯作者：
M. Bishop
中科院分区：
文献类型：
--
作者：
N. Mccarthy;M. Bishop
同种异体干细胞移植用于治疗多种恶性和非恶性血液病。传统上，基于高剂量放化疗的预备方案被认为是肿瘤根除和促进供体干细胞植入的必要条件。现在很明显，免疫介导的移植物抗肿瘤效应在同种异体干细胞移植的治疗潜力中起着关键作用。这促使了毒性较小、非清髓性但具有深度免疫抑制作用的制备方案的发展，通常以氟达拉滨或放射为基础。可以实现完全供体移植；然而，有相当数量的患者达到混合嵌合状态。混合造血嵌合为使用供体淋巴细胞输注的过继免疫疗法提供了一个平台，以最大限度地发挥免疫介导的抗肿瘤作用，但最佳的使用方法尚未确定。非清髓方案的即时手术相关死亡率很低，但移植物抗宿主病仍然是一个主要的临床问题和治疗挑战。主要的肿瘤反应已经在许多血液系统恶性肿瘤中发现，主要包括高度化疗难治性疾病的患者。随访数据很短，需要更多的时间来确定这种免疫疗法的疗效和毒性。该方法具有广泛的临床应用潜力，包括HLA错配和匹配的非亲属供体移植，探索移植物对抗实体瘤效应，以及纠正非恶性疾病的表型表达。
Allogeneic stem cell transplantation is used to treat a variety of malignant and nonmalignant hematologic diseases. Conventionally, high-dose chemoradiotherapy-based preparative regimens were considered essential both for tumor eradication and facilitation of donor stem cell engraftment. It is now apparent that an immune-mediated graft-versus-tumor effect has a pivotal role in the curative potential of allogeneic stem cell transplantation. This has prompted the development of less toxic, nonmyeloablative but profoundly immunosuppressive preparative regimens, often fludarabine- or radiation-based. Full donor engraftment can be achieved; however, a significant number of patients achieve a mixed chimeric state. Mixed hematopoietic chimerism provides a platform for the use of adoptive immunotherapy using donor lymphocyte infusions to maximize the immune-mediated antitumor effect, but the optimal usage has yet to be determined. Immediate procedure-related mortality with nonmyeloablative regimens has been low, but graft-versus-host disease remains a major clinical concern and treatment challenge. Major tumor responses have been seen in many hematologic malignancies primarily including patients with highly chemorefractory disease. Follow-up data have been short and additional time is needed to determine the efficacy and toxicities of this immunotherapy. This approach has potential for widespread clinical application including HLA mismatched and matched unrelated donor transplantation, exploration of a graft-versus-solid tumor effect, and correction of phenotypic expression in nonmalignant disorders.