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Relapse after Allogeneic Hematopoietic Cell Transplantation forMyelodysplastic Syndromes: Analysis of Late Relapse Using Comparative Karyotype andChromosome Genome Array Testing

机译:异基因造血细胞移植后复发骨髓增生异常综合征:使用比较核型和晚期复发分析染色体基因组阵列测试

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摘要

Relapse is a major cause of failure after allogeneic hematopoietic cell transplantation (HCT) in patients with myelodysplastic syndromes (MDS). We analyzed the relapse pattern in 1007 patients who underwent transplantation for MDS to identify factors that may determine the timing of relapse. Overall, 254 patients relapsed: 213 before 18 months and 41 later than 18 months after HCT, a time point frequently used in clinical trials. The hazard of relapse declined progressively with time since transplantation. A higher proportion of patients with early relapse had high-risk cytogenetics compared with patients with late relapse (P =.009). Patients with late relapse had suggestively longer postrelapse survival than patients who relapsed early, although the difference was not statistically significant (P =.07). Among 41 late relapsing patients, sequential cytogenetic data were available in 36. In 41% of these, new clonal abnormalities in addition to pre-HCT findings were identified at relapse; in 30% pre-HCT abnormalities were replaced by new clones, in 17.3% the same clone was present before HCT and at relapse, and in 9.7%, no abnormalities were present either before HCT or at relapse. Comparative chromosomal genomic array testing in 3 patients with late relapse showed molecular differences not detectable by cytogenetics between the pre-HCT clones and the clones at relapse. These data show that late relapses are not infrequent in patientswho undergo transplantation for MDS. The pattern of new cytogenetic alterations at laterelapse is similar to that observed in patients with early relapse and supports theconcept that MDS relapse early and late after HCT is frequently due to the emergence ofclones not detectable before HCT.
机译:复发是骨髓增生异常综合症(MDS)患者异基因造血细胞移植(HCT)后失败的主要原因。我们分析了1007例接受MDS移植的患者的复发模式,以确定可能决定复发时机的因素。总体而言,共有254例患者复发:HCT前18个月为213例,HCT后18个月为18例,这是临床试验中经常使用的时间点。自移植以来,随着时间的推移,复发的风险逐渐降低。与晚期复发的患者相比,早期复发的患者具有较高的细胞遗传学风险(P = .009)。提示晚期复发患者比早期复发患者具有更长的复发后生存期,尽管差异无统计学意义(P = .07)。在41位晚期复发患者中,有36位获得了连续的细胞遗传学数据。在这些患者中,有41%在复发时除了HCT前的发现还发现了新的克隆异常。在30%的HCT之前,异常被新的克隆所替代;在17.3%的HCT之前和复发时,存在相同的克隆;而在9.7%的HCT之前或复发时,均未发现异常。在3例晚期复发患者中进行的比较染色体基因组阵列测试显示,HCT之前的克隆与复发时的克隆之间的细胞遗传学检测不到分子差异。这些数据表明,患者晚期复发并非罕见接受MDS移植的人。晚期新的细胞遗传学改变的模式复发与早期复发患者中观察到的相似,并支持MDS在HCT后早期和晚期复发的概念通常是由于HCT之前无法检测到的克隆。

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