Carella Angelo M
Department of Hematology and BMT Unit, Azienda Ospedaliera e Cliniche Universitarie Convenzionate Ospedale San Martino, Genova, Italy.
Hematol J. 2004;5 Suppl 1:S68-75. doi: 10.1038/sj.thj.6200393.
Allogeneic stem cell transplantation (alloSCT) is an accepted therapeutic option for various hematological malignancies. For many years, alloSCT was based on the concept that a myeloablative dose of chemoradiotherapy was necessary to allow successful donor stem cell engraftment. These high-dose regimens cause considerable toxicity in graft recipients and even the most intensive conditioning regimens do not reliably eliminate all malignant cells. During the last decade, it became clear that the curative potential of alloSCT was not solely due to the conditioning regimen but also to an immune response of donor cells against the malignancy, termed the graft-versus-leukemia (GVL) effect. The increasing evidence that the GVL effect is essential for the eradication of host tumor cells has led to the development of a new concept in alloSCT: the use of reduced intensity, nonmyeloablative conditioning regimens that allow exploitation of the GVL effect without the toxicity of myeloablative therapy. The purine analog fludarabine is immunosuppressive and has activity against many hematological malignancies. The introduction of nonmyeloablative fludarabine-based conditioning regimens has facilitated alloSCT, while limiting regimen-related morbidity and mortality in patients with susceptible hematological malignancies. This potentially curative approach extends the use of alloSCT to older patients and to those with comorbidities that preclude high-dose chemoradiotherapy. The purpose of this review is to summarize the results obtained with fludarabine-based nonmyeloablative conditioning regimens and alloSCT in patients with malignant hematological disorders.
异基因干细胞移植（alloSCT）是治疗多种血液系统恶性肿瘤的一种公认的治疗选择。多年来，alloSCT基于这样一种观念，即需要进行清髓剂量的放化疗才能使供体干细胞成功植入。这些高剂量方案会给移植受者带来相当大的毒性，而且即使是最强化的预处理方案也不能可靠地清除所有恶性细胞。在过去十年中，人们清楚地认识到alloSCT的治愈潜力不仅归因于预处理方案，还归因于供体细胞对恶性肿瘤的免疫反应，即移植物抗白血病（GVL）效应。越来越多的证据表明GVL效应对于根除宿主肿瘤细胞至关重要，这导致了alloSCT新概念 的发展：使用强度降低的非清髓性预处理方案，该方案能够利用GVL效应而无清髓性治疗的毒性。嘌呤类似物氟达拉滨具有免疫抑制作用，对多种血液系统恶性肿瘤有活性。引入基于氟达拉滨的非清髓性预处理方案促进了alloSCT，同时限制了易感血液系统恶性肿瘤患者与方案相关的发病率和死亡率。这种潜在的治愈方法将alloSCT的应用扩展到老年患者以及那些因合并症而不能进行高剂量放化疗的患者。本综述的目的是总结基于氟达拉滨的非清髓性预处理方案和alloSCT在恶性血液疾病患者中取得的结果。
