Clinical lymphoma, myeloma & leukemia · 2025
Identifying Risk Factors and Outcome for CNS Involvement in AML.
СтатьяНазвание и аннотация: Перевод в очереди
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Seki Jack T, Daher-Reyes Georgina S, Atenafu Eshetu G, Sibai Jad, Bankar Aniket, Young Tayler, Chan Steven, Yee Karen, Gupta Vikas, Minden Mark D, Maze Dawn, Schuh Andre, Schimmer Aaron, Sibai Hassan
Аннотация
BACKGROUND: Central nervous system infiltration (CNS+) leads to serious complications in AML. Molecular characteristics associated with CNS disease is not well defined.
MATERIAL AND METHODS: 259 patients received lumbar puncture (LP) and prophylaxis intrathecal (IT) chemotherapy based on neurological symptoms and / or hyperleukocytosis RESULTS: : 31 (11.97%) patients were confirmed CNS+. The most common mutation by Next-generation sequencing (NGS) were NPM1 (48.4%), FLT3 (29.0%), TET2 (25.8%), DNMT3A (19.4%), ASXL1 (16.1%). Univariate analysis, NPM1 (OR: 2.880), FLT3-ITD (OR:3.222), and their combination (OR:3.912) revealed higher incidence in CNS+ . Multivariable analysis, confirmed independent associations with CNS+: WBC ≥100 × 10⁹/L (OR 5.61, P = .0001), WBC ≥30 (OR 3.73, P = .0039), WBC ≥40 (OR 2.93, P = .0149), LDH & NPM1 combined (OR: 2.503) and the presence of an 11q23 abnormality (OR:7.569). WBC count of ≥30 showed the largest separation with CNS+ being 71.0% and CNS- being 29.0% of the cases although it may capture lower-risk patients. In the meantime, a threshold of ≥40 maintained a strong association with CNS+ (64.5%) while improving specificity (35.5%). There is no significant difference in overall survival (OS) (47% vs. 45%) (P = .90) and cumulative incidence of relapse (CIR) (29.0% vs. 15.6%) (P = .06) between CNS positive and negative groups at 36 months CONCLUSION: : Routine screening LP and prophylactic IT chemotherapy should be considered in high-risk AML patients (WBC ≥40×109 /L, elevated LDH and NPM1 mutation, or 11q23 abnormality) to assess for CNS+ and likely preventing the occurrence of CNS relapse. A larger prospective trial is needed to confirm the results.
MATERIAL AND METHODS: 259 patients received lumbar puncture (LP) and prophylaxis intrathecal (IT) chemotherapy based on neurological symptoms and / or hyperleukocytosis RESULTS: : 31 (11.97%) patients were confirmed CNS+. The most common mutation by Next-generation sequencing (NGS) were NPM1 (48.4%), FLT3 (29.0%), TET2 (25.8%), DNMT3A (19.4%), ASXL1 (16.1%). Univariate analysis, NPM1 (OR: 2.880), FLT3-ITD (OR:3.222), and their combination (OR:3.912) revealed higher incidence in CNS+ . Multivariable analysis, confirmed independent associations with CNS+: WBC ≥100 × 10⁹/L (OR 5.61, P = .0001), WBC ≥30 (OR 3.73, P = .0039), WBC ≥40 (OR 2.93, P = .0149), LDH & NPM1 combined (OR: 2.503) and the presence of an 11q23 abnormality (OR:7.569). WBC count of ≥30 showed the largest separation with CNS+ being 71.0% and CNS- being 29.0% of the cases although it may capture lower-risk patients. In the meantime, a threshold of ≥40 maintained a strong association with CNS+ (64.5%) while improving specificity (35.5%). There is no significant difference in overall survival (OS) (47% vs. 45%) (P = .90) and cumulative incidence of relapse (CIR) (29.0% vs. 15.6%) (P = .06) between CNS positive and negative groups at 36 months CONCLUSION: : Routine screening LP and prophylactic IT chemotherapy should be considered in high-risk AML patients (WBC ≥40×109 /L, elevated LDH and NPM1 mutation, or 11q23 abnormality) to assess for CNS+ and likely preventing the occurrence of CNS relapse. A larger prospective trial is needed to confirm the results.