Bock Fabian, Lu Gary, Srour Samer A, Gaballa Sameh, Lin Heather Y, Baladandayuthapani Veerabhadran, Honhar Medhavi, Stich Maximilian, Shah Nina Das, Bashir Qaiser, Patel Krina, Popat Uday, Hosing Chitra, Korbling Martin, Delgado Ruby, Rondon Gabriela, Shah Jatin J, Thomas Sheeba K, Manasanch Elisabet E, Isermann Berend, Orlowski Robert Z, Champlin Richard E, Qazilbash Muzaffar H
Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas; Institute of Clinical Chemistry and Pathobiochemistry, Otto-von-Guericke-University, Magdeburg, Germany.
Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, Texas.
Biol Blood Marrow Transplant. 2016 Dec;22(12):2159-2164. doi: 10.1016/j.bbmt.2016.09.003. Epub 2016 Sep 13.
The gain/amplification of the CKS1B gene on chromosome 1q21 region is associated with a poor outcome in patients with multiple myeloma (MM). However, there are limited data on the outcome of patients with CKS1B amplification after a single high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HCT). We retrospectively evaluated the outcome of patients with CKS1B amplification who received an auto-HCT between June 2012 and July 2014 at our institution. We identified 58 patients with MM and CKS1B gene amplification detected by fluorescent in situ hybridization (FISH). We compared their outcomes with a propensity score-matched control group of 58 patients without CKS1B amplification who were treated at approximately the same time. The primary objective was to compare the progression-free (PFS) and overall survival (OS) between the CKS1B and the control groups. Stratified log-rank test with the matched pairs as strata and double robust estimation under the Cox model were used to assess the effect of CKS1B gene amplification on PFS or OS in the matched cohort. Patients in the CKS1B and control groups were well matched for age, gender, disease status, year of auto-HCT, response to pretransplantation therapy, and baseline hemoglobin level. In both groups, 57% patients were in first remission and 43% had relapsed disease at auto-HCT. Twenty-seven (47%) patients with CKS1B amplification had concurrent monosomy 13 or 13q deletion; 6 (10%) by conventional cytogenetics only, 16 (28%) by FISH only, and 5 (9%) by both. Median follow-up after auto-HCT was 25.4 months. The median PFS of the CKS1B and the control groups were 15.0 months and 33.0 months (P = .002), respectively. The median OS have not been reached yet. The 2-year OS rates in the CKS1B and the control groups were 62% and 91% (P = .02), respectively. In conclusion, Patients with CKS1B amplification are more likely to have additional high-risk cytogenetic abnormalities and a shorter PFS and OS after an auto-HCT.
1号染色体1q21区域CKS1B基因的增益/扩增与多发性骨髓瘤（MM）患者的不良预后相关。然而，关于单剂量大剂量化疗和自体造血干细胞移植（auto-HCT）后CKS1B扩增患者的预后数据有限。我们回顾性评估了2012年6月至2014年7月在我们机构接受auto-HCT的CKS1B扩增患者的预后。我们通过荧光原位杂交（FISH）鉴定出58例MM且CKS1B基因扩增的患者。我们将他们的预后与倾向评分匹配的58例同期接受治疗的无CKS1B扩增的对照组患者进行比较。主要目的是比较CKS1B组和对照组之间的无进展生存期（PFS）和总生存期（OS）。以匹配对为分层的分层对数秩检验和Cox模型下的双重稳健估计用于评估CKS1B基因扩增对匹配队列中PFS或OS的影响。CKS1B组和对照组患者在年龄、性别、疾病状态、auto-HCT年份、移植前治疗反应和基线血红蛋白水平方面匹配良好。两组中，57%的患者处于首次缓解期，43%的患者在auto-HCT时疾病复发。27例（47%）CKS1B扩增患者同时存在13号染色体单体或13q缺失；仅通过传统细胞遗传学检测到6例（10%），仅通过FISH检测到16例（28%），两种方法均检测到5例（9%）。auto-HCT后的中位随访时间为25.4个月。CKS1B组和对照组的中位PFS分别为15.0个月和33.0个月（P = 0.002）。中位OS尚未达到。CKS1B组和对照组的2年OS率分别为62%和91%（P = 0.02）。总之，CKS1B扩增患者更有可能存在其他高危细胞遗传学异常，且auto-HCT后的PFS和OS更短。
