Neutrophil-to-Lymphocyte Ratio As a Prognostic Marker for Elderly Patients with Acute Lymphoblastic Leukemia
Authors: An Joseph B , Williams Lacey Scott , Londono Valeria , Zapata Canto Nidia , Rivero Gustavo A. 
Published: December 2024

Background: Acute lymphoblastic leukemia (ALL) is an uncommon hematological malignancy in adults that involves increased morbidity/mortality as compared to the pediatric and adolescent/young adult (AYA) populations. Although predictive models that aim to estimate long-term survival exist, there is a need to establish markers to be utilized at time of leukemia diagnosis to identify patients at high risk of short-term mortality. Early identification of such groups may help guide clinical decision-making, such as in the adjustment of induction anti-leukemic therapy intensification as well as in the degree of monitoring that may be needed for hospitalized patients. The neutrophil-to-lymphocyte (NLR) ratio has been shown in recent studies to predict clinical outcomes in various malignancies such as AML and solid malignancies, but its utility in ALL is unknown.

Methods: A retrospective analysis was performed utilizing chart review-derived data collected from 49 elderly ALL patients (≥55 years at time of diagnosis) acrossfour institutions (Medstar Georgetown University Hospital, Medstar Washington Hospital Center, Baylor University Medical Center, The National Cancer Institute of Mexico), ranging from a time period of 2004-2023 for time of diagnosis. A multivariate logistic regression analysis with backward elimination to remove effect from model was performed to describe the relationship between NLR and 30- or 60-day mortality. A test for significant difference in the mean NLR value between patients with 30- or 60-day mortality was then performed by a two-tailed Welch's t-test for unequal variance.

Results: In elderly ALL patients over the age of 55, increasing NLR is associated with a significantly increased risk of 30-day mortality (OR = 4.25 [95% CI, 1.50-12.07], p=0.007) and 60-day mortality (OR = 2.47 [1.07-5.66], p=0.034). With multivariate adjustment, increasing NLR was still significantly associated with 30-day mortality (OR = 4.01 [1.21-13.32], p=0.023) but did not meet significance for 60-day mortality (p=0.066), adjusting for age, sex, BMI, race, obesity, diabetes mellitus, HIRISK (high risk cytogenetics or WBC &gt;30K), Philadelphia chromosome positivity, bone marrow blast population percentage, serum uric acid, serum fibrinogen, serum LDH, hemoglobin, platelet count, creatinine, white blood cell count, absolute lymphocyte count, and absolute neutrophil count. There was a significant difference in NLR between patients with (3.32 [0.56-6.09]) or without (0.56 [0.32-0.80], p=0.0485) 30-day mortality, but not in 60-day mortality (p=0.0956).

Conclusion: With each one point increase in the NLR, the odds of 30-day mortality of elderly ALL patients increases by 4-fold, even after adjusting for covariates. This marker could potentially be used in the future as a tool to identify patients at high risk for short-term mortality, which may help inform clinicians on whether to use intensive chemotherapy regimens and monitor patients more rigorously. Investigation into whether NLR predicts mortality in pediatric/AYA ALL patients are underway.