A Multicenter Analysis of Allogeneic Transplant Outcomes in Adults with Philadelphia-like B-cell Acute Lymphoblastic Leukemia in First Complete Remission.
Zaid Abdel Rahman, Tamer Othman, Rima M Saliba, Yenny Alejandra Moreno Vanegas, Razan Mohty, Celina Ledesma, Gabriela Rondon, Nitin Jain, Elias Jabbour, Vinod Pullarkat, Hassan B Alkhateeb, Hagop M Kantarjian, Patricia T Greipp, Ryotaro Nakamura, Mohamed A Kharfan-Dabaja, Richard E Champlin, Stephen J Forman, Elizabeth J Shpall, Mark R Litzow, James M Foran, Ibrahim Aldoss, Paul B Koller, Partow Kebriaei
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Abstract
Background: Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subset of B-cell ALL with a poor prognosis with conventional therapies. Diagnostic challenges and lack of standardized treatment protocols contribute to suboptimal outcomes. Additionally, while allogeneic hematopoietic cell transplantation (HCT) is frequently recommended in adults with Ph-like ALL given its high-risk nature, data supporting its role remains limited.
Objective: We conducted a multicenter retrospective study evaluating outcomes of adult patients undergoing HCT in first complete remission (CR1) for Ph-like ALL compared to Philadelphia chromosome positive ALL (Ph-pos) and other B-cell Philadelphia negative (Ph-neg) ALL.
Study design: Data was collected from from five academic centers across the US, focusing on HCT outcomes for patients with ALL. Patients undergoing HCT in CR1 between 2006 and 2021 were included.
Results: Among 673 patients, 83 (12.3%) had Ph-like ALL, while 271 (40.3%) had Ph-pos and 319 (47.4%) had Ph-neg ALL. Outcomes following HCT in CR1 for Ph-like ALL were comparable to Ph-neg ALL, with no significant differences in 3-year overall survival (66% vs 59%, p=0.1), progression-free survival (59% and 54%, p=0.1), or relapse rates (22% vs 20%, p=0.7). In contrast, Ph-pos ALL had superior outcomes; 3-year OS (75%, p<0.001), PFS (70%, p=0.001) and relapse (12%, p=0.003), this is likely attributed to tyrosine kinase inhibitor therapy.
Conclusion: Our study suggests that HCT, coupled with effective 2nd line therapies can possibly mitigate the poor prognosis associated with Ph-like ALL and offers promising outcomes for patients with Ph-like ALL.
背景：费城样急性淋巴细胞白血病（Ph-like ALL）是B细胞ALL的高危亚型，传统疗法预后较差。诊断难题和标准化治疗方案的缺乏导致疗效不理想。此外，虽然异基因造血细胞移植（HCT）经常被推荐用于高危的成人类Ph-like ALL患者，但支持其作用的数据仍然有限：我们开展了一项多中心回顾性研究，评估了首次完全缓解（CR1）的Ph样ALL成人患者接受HCT治疗的疗效，并与费城染色体阳性ALL（Ph-pos）和其他B细胞费城阴性ALL（Ph-neg）进行了比较：研究设计：从全美五个学术中心收集数据，重点关注ALL患者的HCT疗效。研究结果：在673名患者中，83人（12人）接受了HCT治疗：在673名患者中，83人（12.3%）为Ph-like ALL，271人（40.3%）为Ph-pos ALL，319人（47.4%）为Ph-neg ALL。Ph-样ALL在CR1期接受造血干细胞移植后的结果与Ph-neg ALL相当，3年总生存率（66% vs 59%，P=0.1）、无进展生存率（59%和54%，P=0.1）或复发率（22% vs 20%，P=0.7）均无显著差异。相比之下，Ph-pos ALL 的疗效更佳；3 年 OS（75%，p=0.1），或复发率（22% vs 20%，p=0.7）：我们的研究表明，造血干细胞移植与有效的二线疗法相结合，有可能减轻与Ph-like ALL相关的不良预后，并为Ph-like ALL患者提供有希望的治疗结果。
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