Ertz-Archambault Natalie, Kosiorek Heidi, Slack James L, Lonzo Melissa L, Greipp Patricia T, Khera Nandita, Kelemen Katalin
Department of Internal Medicine, Mayo Clinic Arizona, Phoenix, Arizona.
Division of Health Sciences Research, Mayo Clinic Arizona, Phoenix, Arizona.
Biol Blood Marrow Transplant. 2017 May;23(5):782-789. doi: 10.1016/j.bbmt.2017.02.003. Epub 2017 Feb 9.
Cytogenetic evolution (CGE) in patients with myeloid neoplasms who relapsed after an allogeneic (allo) hematopoietic cell transplantation (HCT) has been evaluated by only few studies. The effect of the CGE on survival of relapsed allo-HCT recipients is not clear. The effect of previously received chemotherapy to induce CGE in this patient population has not been studied. The aims of our study are to (1) characterize the patterns of cytogenetic change in patients with myeloid neoplasms who relapsed after an allo-HCT, (2) evaluate the effect of CGE on survival, and (3) explore the association of CGE with previous chemotherapy (including the lines of salvage therapy, type of induction, and conditioning therapy). Of 49 patients with a myeloid malignancy (27 acute myeloid leukemia [AML], 19 myelodysplastic syndrome [MDS]/myeloproliferative neoplasm [MPN], and 3 chronic myelogenous leukemia) who relapsed after an allo-HCT, CGE was observed in 25 (51%), whereas 24 patients had unchanged cytogenetic findings at relapse. The CGE group carried more cytogenetic abnormalities at original diagnosis. The most frequent cytogenetic change was the acquisition of 3 or more new chromosomal abnormalities followed by acquisition of unbalanced abnormalities, aneuploidy, and emergence of apparently new clones unrelated to the original clone. The CGE cohort had higher proportion of MDS and MPN and fewer patients with de novo AML. Disease risk assessment category showed a trend to higher frequency of high-risk patients in the CGE group, though the difference was not statistically significant. Time from diagnosis to transplantation and time from transplantation to relapse were not different between the CGE and non-CGE groups. CGE and non-CGE cohorts had similar exposures to salvage therapy and to induction chemotherapy, as well as similar conditioning regimens; thus, no particular type of chemotherapy emerged as a predisposing factor to CGE. CGE was associated with significantly shortened post-transplantation and postrelapse survival when compared with those of the non-CGE group (P = .004 and P < .001, respectively). Our results underscore the significance of CGE in progression of myeloid malignancies after an allo-HCT.
仅有少数研究评估了异基因造血细胞移植（allo-HCT）后复发的髓系肿瘤患者的细胞遗传学演变（CGE）。CGE对复发的allo-HCT受者生存的影响尚不清楚。此前接受的化疗在该患者群体中诱导CGE的作用尚未得到研究。我们研究的目的是：（1）描述allo-HCT后复发的髓系肿瘤患者的细胞遗传学变化模式；（2）评估CGE对生存的影响；（3）探讨CGE与先前化疗（包括挽救治疗线数、诱导类型和预处理方案）的关联。在49例allo-HCT后复发的髓系恶性肿瘤患者中（27例急性髓系白血病[AML]、19例骨髓增生异常综合征[MDS]/骨髓增殖性肿瘤[MPN]和3例慢性粒细胞白血病），25例（51%）观察到CGE，而24例患者在复发时细胞遗传学结果未改变。CGE组在初始诊断时携带更多的细胞遗传学异常。最常见的细胞遗传学变化是获得3个或更多新的染色体异常，其次是获得不平衡异常、非整倍体以及出现与原始克隆无关的明显新克隆。CGE队列中MDS和MPN的比例较高，初发AML患者较少。疾病风险评估类别显示CGE组高危患者的频率有升高趋势，尽管差异无统计学意义。CGE组和非CGE组从诊断到移植的时间以及从移植到复发的时间没有差异。CGE队列和非CGE队列在挽救治疗和诱导化疗的暴露情况以及预处理方案方面相似；因此，没有特定类型的化疗成为CGE的诱发因素。与非CGE组相比，CGE与移植后和复发后生存显著缩短相关（分别为P = 0.004和P < 0.001）。我们的结果强调了CGE在allo-HCT后髓系恶性肿瘤进展中的重要性。
