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Chromosome 1q21 aberrations identify ultra high-risk myeloma with prognostic and clinical implications
American Journal of Hematology ( IF 10.1 ) Pub Date : 2022-06-22 , DOI: 10.1002/ajh.26639
Efstathios Kastritis 1 , Magdalini Migkou 1 , Dimitra Dalampira 2 , Maria Gavriatopoulou 1 , Despina Fotiou 1 , Maria Roussou 1 , Nikolaos Kanellias 1 , Ioannis Ntanasis-Stathopoulos 1 , Panagiotis Malandrakis 1 , Foteini Theodorakakou 1 , Aggeliki Sevastoudi 2 , Evangelos Eleutherakis-Papaiakovou 1 , Theodora Triantafyllou 2 , Evangelos Terpos 1 , Eirini Katodritou 2 , Meletios A Dimopoulos 1
Affiliation  

Numerical abnormalities of chromosome 1q (+1q21) are common in patients with newly diagnosed multiple myeloma (MM) but their prognostic impact remains a matter of debate. In addition, the impact of the number of copies of 1q21 is not known. We analyzed 912 consecutive patients with symptomatic MM to evaluate the prognostic implications of +1q21 and of their copy number variations, as assessed by FISH. At the time of initial diagnosis, 249 (27.3%) patients had +1q21, of which 150 (16.4%) had 3 copies and 99 (10.9%) had 4 or more copies. Presence of +1q21 was associated with advanced ISS stage (p = .003), concurrent presence of other cytogenetics aberrations and advanced R-ISS stage (p < .001). Patients with +1q21 had inferior PFS (median 34 vs. 20 months, p < .001) and OS (median 75 vs. 44 months, p < .001) but the copy number of 1q21 had no additional prognostic impact. In multivariate analysis, adjusting for R-ISS, age, treatment and HDM, +1q21 remained an independent prognostic factor both for PFS (p < .001) and OS (p = .008). The detrimental prognostic effect of +1q21 was more profound in R-ISS-3 patients, identifying a subgroup with OS of just 16 months (vs. 46 for R-ISS-3 without +1q21, p < .001). We further validated our findings in an independent cohort of 272 patients. In conclusion, the presence of +1q21 is associated with more advanced disease, inferior PFS, and OS but especially patients with R-ISS-3 disease and +1q21 have a very poor outcome comprising an ultra-high-risk group.

中文翻译:

染色体 1q21 畸变识别具有预后和临床意义的超高危骨髓瘤

染色体 1q (+1q21) 的数值异常在新诊断的多发性骨髓瘤 (MM) 患者中很常见,但其对预后的影响仍存在争议。此外,1q21拷贝数的影响尚不清楚。我们分析了 912 名有症状 MM 的连续患者,以评估 +1q21 及其拷贝数变异的预后影响,如 FISH 评估的那样。在初步诊断时,249 名 (27.3%) 患者有 +1q21,其中 150 名 (16.4%) 有 3 个拷贝,99 名 (10.9%) 有 4 个或更多拷贝。+1q21 的存在与晚期 ISS 阶段 ( p  = .003)、同时存在其他细胞遗传学异常和晚期 R-ISS 阶段 ( p  <.001) 相关。+1q21 患者的 PFS 较差(中位 34 个月 vs. 20 个月,p < .001)和 OS(中位数 75 个月 vs. 44 个月,p < .001),但 1q21 的拷贝数没有额外的预后影响。在多变量分析中,调整 R-ISS、年龄、治疗和 HDM,+1q21 仍然是 PFS ( p  < .001) 和 OS ( p  = .008)的独立预后因素。+1q21 的不利预后影响在 R-ISS-3 患者中更为显着,确定了一个 OS 仅为 16 个月的亚组(而没有 +1q21 的 R-ISS-3 为 46 个月,p  < .001)。我们在一个由 272 名患者组成的独立队列中进一步验证了我们的发现。总之,+1q21 的存在与更晚期的疾病、较差的 PFS 和 OS 相关,但尤其是患有 R-ISS-3 疾病和 +1q21 的患者具有非常差的结果,包括超高风险组。
更新日期:2022-06-22
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