Harousseau Jean-Luc, Attal Michel
Centre Hospitalier Universitaire, Service d'Hématologie, Place Alexis Ricordeau, 44093 Nantes Cedex 01, France.
Blood Rev. 2002 Dec;16(4):245-53. doi: 10.1016/s0268-960x(02)00043-7.
High-dose therapy with autologous stem cell transplantation (ASCT) has been extensively used in the past 15 years in multiple myeloma. The IFM 90 trial has shown that autologous bone marrow transplantation (BMT) is superior to conventional chemotherapy in terms of response rate, event free survival, overall survival. Several other randomized studies confirm that ASCT yields superior complete remission and event free survival rates. However, the benefit for overall survival is not always significant because some patients may receive high-dose therapy at the time of relapse. While ASCT appears to be the treatment of choice for younger patients, a number of questions have been addressed in the past few years (optimal conditioning regimen, best source of stem cells, impact of tandem autotransplants, role of maintenance therapy, results of transplantation in patients over 65 years of age or with renal failure). These issues are addressed in this review. Analysis of large cohorts of patients indicate that a low beta2 microglobulin level and the absence of chromosome 13 abnormalities are associated with a better outcome. However patients with a high-beta2 microglobulin level and chromosome 13 abnormalities, the prognosis is poor even after tandem transplantations. Allogeneic BMT is offered to a minority of younger patients with an HLA identical sibling. Initial series have shown a high-toxic death rate and no survival advantage compared to ASCT. However, allogeneic BMT is possibly the only curative therapy. Reports of CR achieved after infusion of donor lymphoid cells in patients relapsing after allogeneic BMT support the concept of graft versus myeloma effect. Therefore, the objectives of current studies is to reduce transplant related mortality by using earlier BMT, better selection of patients, better graft-versus host prophylaxis or non myeloablative conditioning regimens.
在过去15年中,大剂量自体干细胞移植(ASCT)疗法已在多发性骨髓瘤治疗中得到广泛应用。IFM 90试验表明,自体骨髓移植(BMT)在缓解率、无事件生存期和总生存期方面均优于传统化疗。其他多项随机研究证实,ASCT能产生更高的完全缓解率和无事件生存率。然而,总生存期的获益并不总是显著,因为一些患者可能在复发时才接受大剂量治疗。虽然ASCT似乎是年轻患者的首选治疗方法,但在过去几年中人们探讨了一些问题(最佳预处理方案、最佳干细胞来源、串联自体移植的影响、维持治疗的作用、65岁以上或肾衰竭患者的移植结果)。本综述将探讨这些问题。对大量患者队列的分析表明,低β2微球蛋白水平和无13号染色体异常与较好的预后相关。然而,β2微球蛋白水平高且有13号染色体异常的患者,即使经过串联移植,预后也较差。少数有 HLA 相同同胞的年轻患者可接受异基因BMT。初步研究系列显示,与ASCT相比,异基因BMT的毒性死亡率高且无生存优势。然而,异基因BMT可能是唯一的治愈性疗法。关于异基因BMT后复发患者输注供体淋巴细胞后实现完全缓解的报道支持移植物抗骨髓瘤效应的概念。因此,当前研究的目标是通过采用更早的BMT、更好地选择患者、更好地预防移植物抗宿主病或非清髓性预处理方案来降低移植相关死亡率。