Department of Hematology and Hematopoietic cell transplantation, City of Hope Medical Center, Duarte, California.
Department of Hematology and Oncology, Loma Linda Medical Center, Loma Linda, California.
Biol Blood Marrow Transplant. 2019 Feb;25(2):e41-e45. doi: 10.1016/j.bbmt.2018.09.041. Epub 2018 Oct 5.
Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) is a subset of high-risk B cell ALLs. A large proportion of Ph-like ALL cases carry activating kinase mutations that could potentially allow them to be targeted by tyrosine kinase inhibitors. Ph-like ALL is not an uncommon entity, especially among adults, with a frequency exceeding 20%, including in older patients (>60 years old) with ALL. Ph-like ALL is associated with inferior outcomes across all ages, and studies have consistently shown a higher incidence of persistent postinduction minimal residual disease in patients carrying Ph-like ALL compared with other subgroups of ALL, and this translates into inferior leukemia-related outcomes. The inferior outcome of conventional chemotherapy for Ph-like ALL in adults raises the fundamental question of whether all adults with Ph-like ALL require an allogeneic hematopoietic cell transplantation (HCT) in first complete remission (CR1) regardless of other presenting features and treatment response parameters. Here we present and discuss several scenarios in which adults with Ph-like ALL underwent or were considered for HCT in CR1 for various reasons. Although the decision to proceed with HCT was clear and indisputable in some of these situations, in others we struggled with the decision to transplant in CR1 because of the lack of published data regarding the efficacy of allogeneic HCT as consolidation for Ph-like ALL. We emphasize the urgent need for developing well-designed studies to address this important question.
费城染色体样(Ph-like)急性淋巴细胞白血病(ALL)是高危 B 细胞 ALL 的一个亚组。很大一部分 Ph-like ALL 病例携带激活激酶突变,这些突变可能使它们能够被酪氨酸激酶抑制剂靶向。Ph-like ALL 并不罕见,尤其是在成年人中,其频率超过 20%,包括年龄较大(>60 岁)的 ALL 患者。Ph-like ALL 在所有年龄段的预后均较差,研究一致表明,与其他 ALL 亚组相比,携带 Ph-like ALL 的患者在诱导后持续微小残留病的发生率更高,这转化为较差的白血病相关结局。成人 Ph-like ALL 对常规化疗的不良预后提出了一个基本问题,即无论其他表现特征和治疗反应参数如何,所有 Ph-like ALL 成年患者是否都需要在首次完全缓解(CR1)时进行异基因造血细胞移植(HCT)。在这里,我们提出并讨论了几种情况下,Ph-like ALL 成人患者因各种原因在 CR1 中接受或考虑进行 HCT。尽管在某些情况下,进行 HCT 的决定是明确和无可争议的,但在其他情况下,由于缺乏关于异体 HCT 作为 Ph-like ALL 巩固治疗的疗效的已发表数据,我们在 CR1 中移植的决定存在争议。我们强调迫切需要制定精心设计的研究来解决这个重要问题。