Hematology, Department of Experimental Clinical Medicine, Udine, Italy.
Biol Blood Marrow Transplant. 2012 Apr;18(4):617-26. doi: 10.1016/j.bbmt.2011.07.026. Epub 2011 Aug 3.
Allogeneic stem cell transplantation (allo-SCT) using reduced-intensity conditioning (RIC) is a feasible procedure in selected patients with relapsed multiple myeloma (MM), but its efficacy remains a matter of debate. The mortality and morbidity related to the procedure and the rather high relapse risk make the use of allo-SCT controversial. In addition, the availability of novel antimyeloma treatments, such as bortezomib and immunomodulatory agents, have made allo-SCT less appealing to clinicians. We investigated the role of RIC allo-SCT in patients with MM who relapsed after autologous stem cell transplantation and were then treated with a salvage therapy based on novel agents. This study was structured similarly to an intention-to-treat analysis and included only those patients who underwent HLA typing immediately after the relapse. Patients with a donor (donor group) and those without a suitable donor (no-donor group) were compared. A total of 169 consecutive patients were evaluated retrospectively in a multicenter study. Of these, 75 patients found a donor and 68 (91%) underwent RIC allo-SCT, including 24 from an HLA-identical sibling (35%) and 44 from an unrelated donor (65%). Seven patients with a donor did not undergo allo-SCT for progressive disease or concomitant severe comorbidities. The 2-year cumulative incidence of nonrelapse mortality was 22% in the donor group and 1% in the no-donor group (P < .0001). The 2-year progression-free survival (PFS) was 42% in the donor group and 18% in the no-donor group (P < .0001). The 2-year overall survival (OS) was 54% in the donor group and 53% in the no-donor group (P = .329). In multivariate analysis, lack of a donor was a significant unfavorable factor for PFS, but not for OS. Lack of chemosensitivity after salvage treatment and high-risk karyotype at diagnosis significantly shortened OS. In patients who underwent allo-SCT, the development of chronic graft-versus-host disease had a significant protective effect on OS. This study provides evidence for a significant PFS benefit of salvage treatment with novel drugs followed by RIC allo-SCT in patients with relapsed MM who have a suitable donor.
异基因造血干细胞移植（allo-SCT）采用强度减低预处理（RIC）在选择的复发性多发性骨髓瘤（MM）患者中是一种可行的方法，但疗效仍存在争议。该程序相关的死亡率和发病率以及相当高的复发风险使得 allo-SCT 存在争议。此外，新型骨髓瘤治疗药物（如硼替佐米和免疫调节药物）的应用使得 allo-SCT 对临床医生的吸引力降低。我们研究了在接受自体造血干细胞移植后复发并随后接受新型药物挽救治疗的 MM 患者中 RIC allo-SCT 的作用。这项研究的设计类似于意向治疗分析，仅包括那些在复发后立即进行 HLA 配型的患者。将患者分为有供者（供者组）和无供者（无供者组）。共对 169 例连续患者进行了回顾性多中心研究。其中，75 例患者找到了供者，68 例（91%）接受了 RIC allo-SCT，其中 24 例来自 HLA 完全相同的同胞（35%），44 例来自无关供者（65%）。7 例有供者的患者因疾病进展或同时存在严重合并症而未接受 allo-SCT。供者组 2 年无复发生存率为 22%，无供者组为 1%（P<0.0001）。供者组 2 年无进展生存率（PFS）为 42%，无供者组为 18%（P<0.0001）。供者组 2 年总生存率（OS）为 54%，无供者组为 53%（P=0.329）。多变量分析显示，无供者是 PFS 的显著不利因素，但对 OS 无影响。挽救治疗后无化疗敏感性和诊断时高危核型显著缩短 OS。在接受 allo-SCT 的患者中，慢性移植物抗宿主病的发生对 OS 有显著的保护作用。这项研究为在有合适供者的复发性 MM 患者中，新型药物挽救治疗后进行 RIC allo-SCT 可显著改善 PFS 提供了证据。
