Preprint Article Version 1 This version is not peer-reviewed

Is CNS Involvement in AML Patients predictable? Analyzing Risk Factors, Clinical Outcomes, and the Impact of Next-Generation Sequencing

Jack T. Seki
,
Georgina Daher-Reyes
,
Eshetu G. Atenafu
ORCID logo ,
Jad Sibai
,
Aniket Bankar
,
Tayler Young
,
Steven Chan
,
Karen Yee
ORCID logo ,
Vikas Gupta
,
Mark D. Minden
,
Dawn C. Maze
,
Andre C. Schuh
,
Aaron Schimmer
,
Hassan Sibai
*
Version 1 : Received: 3 October 2024 / Approved: 8 October 2024 / Online: 8 October 2024 (13:23:10 CEST)

How to cite: Seki, J. T.; Daher-Reyes, G.; Atenafu, E. G.; Sibai, J.; Bankar, A.; Young, T.; Chan, S.; Yee, K.; Gupta, V.; Minden, M. D.; Maze, D. C.; Schuh, A. C.; Schimmer, A.; Sibai, H. Is CNS Involvement in AML Patients predictable? Analyzing Risk Factors, Clinical Outcomes, and the Impact of Next-Generation Sequencing. Preprints 2024, 2024100568. https://doi.org/10.20944/preprints202410.0568.v1 Seki, J. T.; Daher-Reyes, G.; Atenafu, E. G.; Sibai, J.; Bankar, A.; Young, T.; Chan, S.; Yee, K.; Gupta, V.; Minden, M. D.; Maze, D. C.; Schuh, A. C.; Schimmer, A.; Sibai, H. Is CNS Involvement in AML Patients predictable? Analyzing Risk Factors, Clinical Outcomes, and the Impact of Next-Generation Sequencing. Preprints 2024, 2024100568. https://doi.org/10.20944/preprints202410.0568.v1

Abstract

CNS infiltration (CNS+) leads to serious complications in AML. Cytogenetic and Molecular profile is essential in risk stratification, treatment decisions and envisage prognosis. We utilize the NGS data and cytogenetics as a screening tool, for determining the incidences and specific CNS+ risks, in patients eligible for intrathecal chemotherapy. 52 mutations database per NGS was used for the analysis. 435 newly diagnosed patients underwent frontline induction chemotherapy. 259 (59.5%) patients received LP. The most common molecular mutation in the CNS+ patients were MPN1 (48.3%), FLT3 (22.5%), TET2 (25.8%), RAS / KRAS (25.7%), DMNT3 (19.3%), ASXL1 and (16.1%). Of which 31 patients had confirmed CNS+ disease due to the presence of characteristic markers. CNS+ patients have significantly higher bone marrow blast% (76 vs. 53) (p= 0.0202). WBC count ≥ 100x109/L (OR: 5.614 [2.313-13.626] p=0.0001) in the multivariable analysis, and LDH ≥2ULN (OR: 5.512 [2.176-13.965]; p= 0.0003) in the univariate analysis, revealed higher risk for CNS+. Patients exhibited significantly higher NPM1 mutations (48.4% vs 24.6%, p=0.0053) and 11q23 chromosomal abnormality (12.9% vs 2.19%, p= 0.0139). However, FLT3 by NGS did not predict CNS+ (P=0.1226). CNS+ did not contribute significantly toward CIR (p=0.066), and has no bearing on OS (p=0.9063). Patients presented with either neurological symptoms or accompanied by hyperleukocytosis, elevated LDH, NPM1 positivity or 11q23 abnormality are highly suggestive of CNS+. Therefore, LP is needed to rule-out CNS disease at presentation. NGS did not consistently predict CNS+. A large prospective trial is needed to confirm the results.

Keywords

Acute Myeloid Leukemia; CNS infiltration; Molecular Profile; NGS; Risk factors and Outcomes

Subject

Medicine and Pharmacology, Hematology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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