The gain/amplification CKS1B gene at chromosome region 1q21 (1q+) is one of the most common genetic aberrations in multiple myeloma (MM). Amplification of CKS1B is frequently associated with the deletion of the CDKN2C gene at chromosome region 1p32 (1p-), which is also associated with inferior outcomes. In this retrospective study, we evaluated the outcomes of patients with 1q+ and/or 1p- after high-dose therapy and autologous hematopoietic cell transplantation (auto-HCT). From January 2006 to December 2015, 1491 newly diagnosed patients with MM underwent upfront high-dose therapy and auto-HCT at our institution. Of those, 899 had the fluorescent in situ hybridization (FISH) data available. FISH was performed at diagnosis and before the start of induction in 686 (76%) patients and after the initiation of induction therapy in 213 (24%) patients. We identified 100 patients with 1q+ and/or 1p- by FISH from the cohort of 899 patients. A control group (n = 287) with diploid cytogenetics and normal FISH panel was selected from the same cohort. From the above 2 cohorts, using a propensity score matched analysis, we identified matched controls for 85 of the 100 patients with 1q+/1p-. Patients were matched for age at auto-HCT, sex, International Staging System stage, induction regimen, creatinine level, disease status at auto-HCT, conditioning regimen, and maintenance therapy. Sixty-seven (79%), 4 (5%), and 14 (16%) patients had 1q+, 1p-, or both 1q+ and 1p-, respectively. There was no significant difference in induction therapy, preparative regimen, or maintenance therapy between the 1q+/1p- and the control group. The median follow-up time for all patients was 29.2 months (range, 0.29 to 84.96). The cumulative incidence of 100-day nonrelapse mortality was 1.2% and 0% for the 1q+/1p- and the control group, respectively. Forty-two patients (50%) in the 1q+/1p- group achieved complete response compared with 40 patients (47%) in the control group. The estimated 3-year progression-free survival (PFS) and overall survival (OS) rates were 41% and 79% for the 1q+/1p- group and 56% and 86% for the control group. Patients in the 1q+/1p- group were at significantly increased risk of progression or death compared to the control group (hazard ratio [HR], 2.21; confidence interval [CI], 1.18 to 4.16; P = .014). No significant association between OS in the 2 groups was observed. The outcome of the 1q+/1p- alone (with no additional high-risk cytogenetics) and the propensity score matched control groups was also compared. Median PFS for the 1q+/1p- alone subgroup was 26.6 months, compared with 38.8 months for the control group (HR, 1.9; CI, 0.9 to 4.08; P = .09). The median OS had not been reached for the 1q+/1p- alone subgroup and was 81.1 months for the control group (HR, 1.25; CI, 0.3 to 4.6; P= .73). 1q+/1p- abnormalities with amplification of CKS1B and deletion ofCDKN2Cgenes were associated with shorter PFS compared with a propensity score matched group of patients with diploid cytogenetics and normal a FISH panel. The outcomes of 1q+/1p- patients with MM have improved with the use of more effective induction, conditioning, and maintenance therapy compared with historical controls, but we still need more effective therapeutic approaches to fully overcome the negative impact of 1q+/1p-.

中文翻译：

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自体造血干细胞移植后具有染色体 1q 增益和 1p 缺失的多发性骨髓瘤的结果：倾向评分匹配分析。

染色体区域 1q21 (1q+) 的增益/扩增 CKS1B 基因是多发性骨髓瘤 (MM) 中最常见的遗传畸变之一。CKS1B 的扩增通常与染色体区域 1p32 (1p-) 处 CDKN2C 基因的缺失有关，这也与较差的结果有关。在这项回顾性研究中，我们评估了 1q+ 和/或 1p- 患者在高剂量治疗和自体造血细胞移植 (auto-HCT) 后的结果。2006 年 1 月至 2015 年 12 月，1491 名新诊断的 MM 患者在我院接受了前期大剂量治疗和自体 HCT。其中，899 个具有可用的荧光原位杂交 (FISH) 数据。686 名 (76%) 患者在诊断时和诱导开始前进行 FISH，213 名 (24%) 患者在诱导治疗开始后进行 FISH。我们从 899 名患者的队列中通过 FISH 确定了 100 名 1q+ 和/或 1p- 患者。从同一队列中选择具有二倍体细胞遗传学和正常 FISH 面板的对照组 (n = 287)。从上述 2 个队列中，使用倾向评分匹配分析，我们为 100 名 1q+/1p- 患者中的 85 名确定了匹配的对照。患者在 auto-HCT 时的年龄、性别、国际分期系统分期、诱导方案、肌酐水平、auto-HCT 时的疾病状态、预处理方案和维持治疗方面进行了匹配。67 名 (79%)、4 名 (5%) 和 14 名 (16%) 患者分别有 1q+、1p- 或 1q+ 和 1p-。1q+/1p- 组和对照组在诱导治疗、准备方案或维持治疗方面没有显着差异。所有患者的中位随访时间为 29.2 个月（范围，0.29 至 84.96）。1q+/1p- 和对照组的 100 天非复发死亡率的累积发生率分别为 1.2% 和 0%。1q+/1p- 组有 42 名患者 (50%) 达到完全缓解，而对照组为 40 名患者 (47%)。1q+/1p- 组的估计 3 年无进展生存 (PFS) 和总生存 (OS) 率分别为 41% 和 79%，对照组为 56% 和 86%。与对照组相比，1q+/1p- 组患者的进展或死亡风险显着增加（风险比 [HR]，2.21；置信区间 [CI]，1.18 至 4.16；P = .014）。未观察到两组的 OS 之间存在显着关联。还比较了单独 1q+/1p- 的结果（没有额外的高风险细胞遗传学）和倾向评分匹配的对照组。1q+/1p- 单独亚组的中位 PFS 为 26.6 个月，而对照组为 38.8 个月（HR，1.9；CI，0.9 至 4.08；P = .09）。1q+/1p- 单独亚组的中位 OS 尚未达到，对照组为 81.1 个月（HR，1.25；CI，0.3 至 4.6；P= .73）。与具有二倍体细胞遗传学和正常 FISH 面板的倾向评分匹配组相比，具有 CKS1B 扩增和 CDKN2C 基因缺失的 1q+/1p- 异常与更短的 PFS 相关。与历史对照相比，1q+/1p- MM 患者的预后随着使用更有效的诱导、调理和维持治疗而有所改善，但我们仍然需要更有效的治疗方法来完全克服 1q+/1p- 的负面影响。对照组为 8 个月（HR，1.9；CI，0.9 至 4.08；P = .09）。1q+/1p- 单独亚组的中位 OS 尚未达到，对照组为 81.1 个月（HR，1.25；CI，0.3 至 4.6；P= .73）。与具有二倍体细胞遗传学和正常 FISH 面板的倾向评分匹配组相比，具有 CKS1B 扩增和 CDKN2C 基因缺失的 1q+/1p- 异常与更短的 PFS 相关。与历史对照相比，1q+/1p- MM 患者的预后随着使用更有效的诱导、调理和维持治疗而有所改善，但我们仍然需要更有效的治疗方法来完全克服 1q+/1p- 的负面影响。对照组为 8 个月（HR，1.9；CI，0.9 至 4.08；P = .09）。1q+/1p- 单独亚组的中位 OS 尚未达到，对照组为 81.1 个月（HR，1.25；CI，0.3 至 4.6；P= .73）。与具有二倍体细胞遗传学和正常 FISH 面板的倾向评分匹配组相比，具有 CKS1B 扩增和 CDKN2C 基因缺失的 1q+/1p- 异常与更短的 PFS 相关。与历史对照相比，1q+/1p- MM 患者的预后随着使用更有效的诱导、调理和维持治疗而有所改善，但我们仍然需要更有效的治疗方法来完全克服 1q+/1p- 的负面影响。CI，0.3 至 4.6；P = .73）。与具有二倍体细胞遗传学和正常 FISH 面板的倾向评分匹配组相比，具有 CKS1B 扩增和 CDKN2C 基因缺失的 1q+/1p- 异常与更短的 PFS 相关。与历史对照相比，1q+/1p- MM 患者的预后随着使用更有效的诱导、调理和维持治疗而有所改善，但我们仍然需要更有效的治疗方法来完全克服 1q+/1p- 的负面影响。CI，0.3 至 4.6；P = .73）。与具有二倍体细胞遗传学和正常 FISH 面板的倾向评分匹配组相比，具有 CKS1B 扩增和 CDKN2C 基因缺失的 1q+/1p- 异常与更短的 PFS 相关。与历史对照相比，1q+/1p- MM 患者的预后随着使用更有效的诱导、调理和维持治疗而有所改善，但我们仍然需要更有效的治疗方法来完全克服 1q+/1p- 的负面影响。