Although high-dose therapy and autologous stem cell transplant combined with novel agents continues to be the hallmark of first-line treatment in newly diagnosed transplant-eligible multiple myeloma patients, the impact of tandem autologous or autologous/reduced-intensity allogeneic transplant for patients with extramedullary disease (EMD) and high-risk cytogenetics is not yet defined. Here, we analyzed clinical and cytogenetic data from 488 adult myeloma patients with EMD undergoing single autologous (n = 373), tandem autologous (n = 84), or autologous-allogeneic transplant (n = 31) between 2003 and 2015. At least 1 high-risk abnormality was present in 41% (n = 202), with del(17p) (40%) and t(4;14) (45%) the most frequent. More than 1 high-risk abnormality was found in 54%. High-risk cytogenetics showed worse 4-year overall survival (OS) and progression-free survival (PFS) of 54% and 29%, respectively, versus 78% and 49% for standard-risk cytogenetics (P < .001). Co-segregation of high-risk abnormalities did not seem to affect outcome. Regarding transplant regimen, OS and PFS were 70% and 43% for single autologous versus 83% and 52% for tandem autologous and 88% and 58% for autologous-allogeneic (P = .06 and P = .30). In multivariate analysis high-risk cytogenetics were associated with worse survival (hazard ratio [HR], 2.00; P = .003), whereas tandem autologous significantly improved outcome versus single autologous transplant (HRs, .46 and .64; P = .02 and P = .03). Autologous-allogeneic transplant did not significantly differ in outcome but appeared to improve survival, but results were limited because of small population (HR, .31). In conclusion, high-risk cytogenetics is frequently observed in newly diagnosed myeloma with EMD and significantly worsens outcome after single autologous, whereas a tandem autologous transplant strategy may overcome onset poor prognosis.

中文翻译：

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串联自体干细胞移植改善了新诊断的多发性骨髓瘤伴髓外疾病和高危细胞遗传学的结果：一项来自欧洲血液和骨髓移植学会慢性恶性肿瘤工作组的研究。

尽管高剂量疗法和自体干细胞移植结合新型药物仍然是新诊断的适合移植的多发性骨髓瘤患者的一线治疗的标志，但自体或自体/强度降低的异体异体移植串联治疗对多发性骨髓瘤患者的影响髓外疾病（EMD）和高危细胞遗传学尚未定义。在这里，我们分析了2003年至2015年间接受单次自体（n = 373），串联自体（n = 84）或自体-异体移植（n = 31）的488例EMD成年骨髓瘤患者的临床和细胞遗传学数据。至少1高风险异常的发生率为41％（n = 202），最常见的是del（17p）（40％）和t（4; 14）（45％）。在54％的人中发现了1个以上的高风险异常。高风险细胞遗传学显示较差的4年总生存率（OS）和无进展生存期（PFS）分别为54％和29％，而标准风险细胞遗传学则分别为78％和49％（P <.001）。高风险异常的共同隔离似乎并未影响预后。关于移植方案，单自体的OS和PFS分别为70％和43％，而串联自体的OS和PFS分别为83％和52％，自体-异体的为88％和58％（P = .06和P = .30）。在多变量分析中，高风险的细胞遗传学与较差的生存率相关（危险比[HR]，2.00； P = .003），而与单次自体移植相比，串联自体显着改善了预后（HR，.46和.64； P = .02和P = .03）。自体同种异体移植的结局无明显差异，但似乎可以改善生存率，但由于人口少，结果有限（HR，.31）。总之，在新诊断为EMD的骨髓瘤中经常观察到高风险的细胞遗传学，并且单次自体移植后结局会明显恶化，而串联自体移植策略可能会克服不良的预后。