Clonal evolution defines risk stratification for central nervous system leukemia in adult acute lymphoblastic leukemia.
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It is well established that central nervous system leukemia (CNSL) is an adverse prognostic factor in acute lymphoblastic leukemia (ALL), yet whether prognostic heterogeneity reside in CNSL is less addressed. Therefore, we aimed to develop potential risk classification for CNSL. We retrospectively analyzed a study in PDT-ALL-2016 pediatric-inspired cohort (N = 494). Flow cytometry (FCM) and next-generation sequencing (NGS) were tested on bone marrow (BM) and cerebrospinal fluid (CSF). The 5-year OS of 437 non-CNSL patients was 62.3% and 33.7% in 57 CNSL patients (P < 0.001). 57 CNSL including 16 primary CNS involvement and 41 CNS relapse patients were divided into 3 groups. The 5-year OS was 48.9% in patients with concordant FCM and NGS between BM and CSF, which were defined as non-clonal evolutionary CNSL, a standard-risk subgroup, while the 5-year OS was 30.2% in patients with discordant FCM or NGS between BM and CSF and isolated CNS relapse (P < 0.05), which were defined as clonal evolutionary CNSL, a high-risk subgroup. Furthermore, the mean times of lumbar punctures to achieve complete remission (CR) in CSF was 4.14 in clonal evolutionary CNSL, comparing to 1.62 in non-clonal evolutionary CNSL (P < 0.05). Based on the evidence of clonal evolution, we develop a risk stratification for CNSL for the first time.