移植前染色体基因组阵列检测改善骨髓纤维化移植患者的预后。

IF 3.6 3区医学 Q2 HEMATOLOGY

Transplantation and Cellular Therapy Pub Date : 2025-03-01 DOI:10.1016/j.jtct.2024.12.018

Xiaoyu Qu , Emily Stevens , Matthew P. Fitzgibbon , Lan Beppu , Tim M. Monahan , Cecilia Yeung , Derek L. Stirewalt , David Wu , Jerald P. Radich , H. Joachim Deeg , Min Fang

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引用次数: 0

摘要

背景：尽管与核型和FISH研究相比，染色体基因组阵列检测（CGAT）对染色体异常的诊断率更高，但它并未被用作骨髓纤维化的常规临床检测。同时，尽管存在许多预后系统在诊断时对患者进行风险分层，但用于预测移植结果的工具有限。目的：本研究旨在检测移植前获得的CGAT结果与目前的风险分类系统DIPSS +相比，是否能改善骨髓纤维化患者移植后的预后。研究设计：我们研究了2000年至2017年间在本中心接受造血细胞移植的骨髓纤维化患者（n=44）。我们评估了CGAT、DIPSS +和基因突变总数对移植后临床结果的预后意义，包括无复发生存期（RFS）、总生存期（OS）和移植物抗宿主病（GVHD）。结果：24例患者（55%）出现CGAT结果异常，其中18例为拷贝中性杂合性缺失（cnLOH, 41%）。从CGAT样本日期开始的中位随访为91个月（范围2-258），RFS为59%，OS为68%。结果分析显示CGAT（正常与异常）具有显著的预后意义，特别是对于DIPSS-plus评分为中等风险的患者和0 ~ 2突变的患者。单独的CGAT对患者的RFS结果有显著的分层（P=0.03）。在DIPSS-plus中添加CGAT将显著性P值从0.08提高到0.003，在突变数中添加CGAT将显著性P值从0.02提高到0.01。当综合考虑CGAT、DIPSS-plus和突变计数时，获得了RFS的最佳分层系统（P = 1e-08）。目前的研究还证实了个体异常的预后意义，包括U2AF1突变（n=5， P=0.03）和1q增益（n=3， P=0.01），它们与较差的RFS相关。ASXL1突变（n=14）似乎与慢性GVHD的晚发相关（P=0.03）。结论：移植前CGAT分析增加了现有的风险分层工具，可作为骨髓纤维化的常规临床检测。

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Pretransplant Chromosome Genomic Array Testing Improves Prognostication for Myelofibrosis Patients Undergoing Transplantation

Background

Despite its known superior diagnostic yield for chromosomal anomalies compared with karyotype and fluorescence in situ hybridization (FISH) studies, chromosome genomic array testing (CGAT) is not used as a routine clinical test for myelofibrosis. Although many prognostic systems exist that risk stratify patients at diagnosis, limited tools are available to prognosticate transplant outcome.

Objective

The current study aimed at testing whether CGAT results obtained before transplantation improves prognosis of post-transplant outcome in patients with myelofibrosis compared with current risk categorization systems, for example, DIPSS plus (Dynamic International Prognostic Scoring System).

Study Design

We studied patients with myelofibrosis who underwent hematopoietic cell transplantation between 2000 and 2017 at our center (N = 44). We assessed the prognostic significance of CGAT, DIPSS plus, and the total count of gene mutations for post-transplant clinical outcomes, including relapse-free survival (RFS), overall survival (OS), and graft-versus-host-disease (GVHD).

Results

Abnormal CGAT results were seen in 24 patients (55%), including 18 with copy-neutral loss of heterozygosity (cnLOH, 41%). With a median follow-up of 91 (range 2-258) months starting from the CGAT sample date, RFS was 59% and OS was 68%. The outcome analysis showed significant prognostic implication from CGAT (normal vs. abnormal), specifically for patients with intermediate risk by DIPSS-plus scores and those with 0∼2 mutations. CGAT alone significantly stratified the patients’ RFS outcome (P = .03). The addition of CGAT to DIPSS-plus improved the significance from a P value of .08 to .003, whereas the addition of CGAT to mutation count improved the P value from .02 to .01. The best stratification system for RFS was achieved when CGAT, DIPSS-plus, and mutation count were all considered (P = 1e-08). The current study also confirmed individual anomalies that are prognostically significant, including U2AF1 mutation (n = 5, P = .03) and 1q gain (n = 3, P = .01), which were associated with worse RFS. ASXL1 mutations (n = 14) appeared to associate with a later onset of chronic GVHD (P =.03).