University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
EBMT Statistical Unit, Leiden, The Netherlands.
Biol Blood Marrow Transplant. 2019 Nov;25(11):2134-2142. doi: 10.1016/j.bbmt.2019.07.004. Epub 2019 Jul 6.
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.
尽管高剂量治疗和自体干细胞移植联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一线治疗的标志，但对于有髓外疾病（EMD）和高风险细胞遗传学的患者，串联自体或自体/低强度同种异体移植的影响尚未确定。在这里，我们分析了 2003 年至 2015 年间 488 例接受单自体（n=373）、串联自体（n=84）或自体-异体移植（n=31）的有 EMD 的成人骨髓瘤患者的临床和细胞遗传学数据。至少存在 1 种高风险异常，占 41%（n=202），其中 del(17p)（40%）和 t(4;14)（45%）最为常见。54%的患者存在多种高风险异常。高风险细胞遗传学显示，4 年总生存率（OS）和无进展生存率（PFS）分别为 54%和 29%，而标准风险细胞遗传学分别为 78%和 49%（P<0.001）。高风险异常的共分离似乎并不影响结果。关于移植方案，单自体组的 OS 和 PFS 分别为 70%和 43%，串联自体组为 83%和 52%，自体-异体组为 88%和 58%（P=0.06 和 P=0.30）。多变量分析显示，高风险细胞遗传学与生存不良相关（风险比 [HR]，2.00；P=0.003），而串联自体与单自体移植相比，结果显著改善（HRs，0.46 和 0.64；P=0.02 和 P=0.03）。自体-异体移植的结果没有显著差异，但似乎改善了生存，但由于患者数量较少，结果有限（HR，0.31）。总之，新诊断的多发性骨髓瘤伴 EMD 中常观察到高风险细胞遗传学，且在单自体治疗后显著恶化，而串联自体移植策略可能克服预后不良。
