Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research.
Department of Computational and Quantitative Medicine.
Blood Adv. 2022 Sep 13;6(17):4936-4948. doi: 10.1182/bloodadvances.2022007597.
Allogenic hematopoietic cell transplantation (alloHCT) is a well-established curative modality for acute lymphoblastic leukemia (ALL), yet large amounts of data describing alloHCT outcomes in Philadelphia (Ph)-like ALL are lacking. We retrospectively analyzed archived DNA samples from consecutive adults with B-cell Ph-negative ALL who underwent alloHCT in complete remission (CR) (n = 127) at our center between 2006 and 2020. Identification of fusions associated with Ph-like ALL was performed using cumulative results from RNA-seq, conventional cytogenetics, fluorescence in situ hybridization, and whole genome array studies. Fusions associated with Ph-like ALL were detected in 56 (44%) patients, of whom 38 were carrying CRLF2r. Compared with other non-Ph-like ALL (n = 71), patients with fusions associated with Ph-like ALL were more frequently Hispanic (P = .008), were less likely to carry high-risk cytogenetics (P < .001), and were more likely to receive blinatumomab prior to HCT (P = .019). With the median followup of 3.5 years, patients with Ph-like ALL fusions had comparable posttransplant outcomes compared with other B-cell ALL: 3-year relapse-free survival (RFS) (41% vs 44%; P = .36), overall survival (OS) (51% vs 50%; P = .59), and relapse (37% vs 31%; P = .47). In multivariable analysis, age (P = .023), disease status at the time of transplant (P < .001), and donor type (P = .015) influenced OS. RFS (primary endpoint) was significantly influenced by disease status (P < .001) and conditioning regimen intensity (P = .014). In conclusion, our data suggest that alloHCT consolidation results in similarly favorable survival outcomes in adult patients with Ph-like fusions and other high-risk B-cell ALL.
同种异体造血细胞移植(alloHCT)是治疗急性淋巴细胞白血病(ALL)的一种成熟方法,但缺乏大量描述费城(Ph)样 ALL alloHCT 结果的数据。我们回顾性分析了 2006 年至 2020 年期间在我中心接受完全缓解(CR)alloHCT 的连续 B 细胞 Ph 阴性 ALL 成年患者的存档 DNA 样本(n = 127)。使用 RNA-seq、常规细胞遗传学、荧光原位杂交和全基因组阵列研究的累积结果来鉴定与 Ph 样 ALL 相关的融合。在 56 名(44%)患者中检测到与 Ph 样 ALL 相关的融合,其中 38 名患者携带 CRLF2r。与其他非 Ph 样 ALL(n = 71)相比,与 Ph 样 ALL 相关融合的患者更常为西班牙裔(P =.008),不太可能携带高危细胞遗传学(P <.001),并且更有可能在 HCT 前接受blinatumomab(P =.019)。中位随访 3.5 年后,与 Ph 样 ALL 融合的患者与其他 B 细胞 ALL 的移植后结果相似:3 年无复发生存率(RFS)(41% vs 44%;P =.36),总生存率(OS)(51% vs 50%;P =.59),和复发(37% vs 31%;P =.47)。多变量分析显示,年龄(P =.023)、移植时疾病状态(P <.001)和供者类型(P =.015)影响 OS。RFS(主要终点)显著受疾病状态(P <.001)和预处理方案强度(P =.014)的影响。总之,我们的数据表明,alloHCT 巩固治疗可使携带 Ph 样融合和其他高危 B 细胞 ALL 的成年患者获得相似的生存获益。