Rasche Leo, Röllig Christoph, Stuhler Gernot, Danhof Sophia, Mielke Stephan, Grigoleit Goetz Ulrich, Dissen Lea, Schemmel Lea, Middeke Jan Moritz, Rücker Viktoria, Schreder Martin, Schetelig Johannes, Bornhäuser Martin, Einsele Hermann, Thiede Christian, Knop Stefan
Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.
Department of Internal Medicine I, Carl Gustav Carus University, Dresden, Germany.
Biol Blood Marrow Transplant. 2016 Nov;22(11):1988-1996. doi: 10.1016/j.bbmt.2016.08.024. Epub 2016 Aug 31.
Although generally not applied as first-line treatment of multiple myeloma, allogeneic hematopoietic cell transplantation (allo-SCT) can still be chosen as ultimate escalation approach in high-risk patients, preferentially within the framework of clinical trials. In this study, we investigated whether decreasing donor chimerism (DC) is predictive for relapse. In addition, we comprehensively determined the impact of several other disease- and treatment-related factors on outcome. One hundred fifty-five multiple myeloma patients whose DC status was followed serially by the short tandem repeat-based techniques at a single lab were included in this retrospective study. Outcome variables were studied in univariate and multivariable analyses. Available were 2.324 DC samples (median, 12 per patient). Loss of full DC was associated with shorter progression-free survival (PFS) (HR, 1.7; 95% CI, 1.1 to 2.6) but did not impact overall survival. Two-thirds of patients with International Myeloma Working Group-defined relapses still displayed a full DC in peripheral blood or bone marrow. Extramedullary manifestations were observed in 33% of patients, accounting for the discrepancy between DC analysis and the actual disease status. In multivariable analysis, the 2 most relevant variables for an unfavorable PFS were progressive disease before allo-SCT (HR, 3.0; 95% CI, 1.5 to 5.9) and allo-SCT at least the second relapse (HR, 2.8; 95% CI, 1.5 to 4.9), whereas for overall survival progressive disease or partial response before allo-SCT had the strongest negative effects (HR, 4.2; 95% CI, 1.9 to 9, and HR, 2.0; 95% CI, 1.0 to 3.8, respectively). Adverse cytogenetics such as del17p, t(4,14) or amp(1q21) were not associated with shorter survival after allo-SCT. Extensive DC sampling beyond robust engraftment does not appear to provide additional information helpful for disease management in most patients and is challenged by a significant incidence of extramedullary disease. In our series, allo-SCT overcame unfavorable cytogenetics.
尽管异基因造血细胞移植（allo-SCT）一般不作为多发性骨髓瘤的一线治疗方法，但对于高危患者，仍可将其作为最终的强化治疗手段，优先考虑在临床试验框架内进行。在本研究中，我们调查了供体嵌合率降低（DC）是否可预测复发。此外，我们全面确定了其他一些疾病和治疗相关因素对预后的影响。本回顾性研究纳入了155例多发性骨髓瘤患者，这些患者的DC状态在单个实验室通过基于短串联重复序列的技术进行连续监测。在单变量和多变量分析中研究了预后变量。共有2324份DC样本（中位数为每位患者12份）。完全DC的丧失与无进展生存期（PFS）缩短相关（HR，1.7；95%CI，1.1至2.6），但不影响总生存期。国际骨髓瘤工作组定义的复发患者中有三分之二在外周血或骨髓中仍显示完全DC。33%的患者观察到髓外表现，这解释了DC分析与实际疾病状态之间的差异。在多变量分析中，对PFS不利的两个最相关变量是allo-SCT前的疾病进展（HR，3.0；95%CI，1.5至5.9）和至少第二次复发时进行allo-SCT（HR，2.8；95%CI，1.5至4.9），而对于总生存期，allo-SCT前的疾病进展或部分缓解具有最强的负面影响（HR分别为4.2；95%CI，1.9至9和HR，2.0；95%CI，1.0至3.8）。不良细胞遗传学如del17p、t(4,14)或amp(1q21)与allo-SCT后的生存期缩短无关。在大多数患者中，除了稳固植入后进行广泛的DC采样似乎并不能提供有助于疾病管理的额外信息，并且受到髓外疾病高发生率的挑战。在我们的系列研究中，allo-SCT克服了不良细胞遗传学的影响。
