Acute leukemia remains the most common form of cancer in children, accounting for nearly one-third of all pediatric malignancies (1). Among the subtypes, acute lymphoblastic leukemia (ALL) is the most prevalent, followed by acute myeloid leukemia (AML) (2). Despite significant advances in treatment, complications arising from leukemic infiltration into various organ systems, particularly the central nervous system (CNS), continue to pose significant challenges in diagnosis, prognosis, and therapeutic strategies (3).

Central nervous system involvement in pediatric acute leukemia is both a clinical and biological concern, as it often signifies a more aggressive disease course and can negatively impact overall outcomes (4). Leukemic cells can infiltrate the meninges and parenchyma, leading to neurological symptoms such as headaches, seizures, cranial nerve palsies, or even altered levels of consciousness. Importantly, CNS infiltration may occur at the time of diagnosis or develop as a relapse, making early identification and risk stratification critical components of patient management (5).

Hematological parameters such as white blood cell (WBC) count, hemoglobin (Hb) levels, and platelet (Plt) counts are commonly used not only in the diagnosis of leukemia but also in monitoring disease progression and response to therapy (6). Elevated WBC counts at diagnosis, for instance, have been associated with a higher risk of CNS involvement, reflecting a higher burden of disease and the propensity for leukemic cells to penetrate the blood-brain barrier. Conversely, anemia and thrombocytopenia, while less specific, may signal bone marrow suppression or infiltration (7).

Lactate dehydrogenase (LDH), an intracellular enzyme released during tissue breakdown or cell turnover, serves as a valuable biomarker for tumor burden and cell lysis (8). Elevated LDH levels are frequently observed in children with acute leukemia and are often indicative of a high proliferative rate and extensive leukemic involvement. Importantly, some studies suggest that increased LDH levels may correlate with CNS infiltration, making it a potentially useful indicator of extra medullary disease (9).

The relationship between CNS involvement and alterations in WBC, Hb, Plt, and LDH levels is complex and multifactorial. While these parameters individually offer diagnostic and prognostic insights, their combined evaluation may enhance the early detection of CNS disease and help in refining treatment regimens (10). For instance, a patient presenting with hyper leukocytosis, anemia, thrombocytopenia, and elevated LDH at diagnosis may warrant closer CNS surveillance or even preemptive CNS-directed therapy (11).

Risk stratification at diagnosis is a cornerstone of modern pediatric leukemia management, with various clinical, hematological, and molecular markers used to guide treatment intensity. Incorporating CNS status and associated hematological markers into risk assessment models may improve outcome prediction and enable more personalized therapeutic approaches. This is particularly important as both overtreatment and under treatment of CNS involvement carry significant risks, including long-term neurotoxicity or disease recurrence (12).

In clinical practice, cerebrospinal fluid (CSF) analysis remains the gold standard for detecting CNS leukemia. However, it is an invasive procedure and may not always detect minimal residual disease or early CNS infiltration (13). Therefore, identifying non-invasive biomarkers or combinations of peripheral blood indicators, such as WBC, Hb, Plt, and LDH, could complement CSF analysis and improve diagnostic accuracy without additional procedural burden (14).

The importance of early and accurate detection of CNS involvement cannot be overstated, as it directly influences the therapeutic approach, including the need for intrathecal chemotherapy, cranial irradiation, or systemic intensification (15). Moreover, CNS relapse remains a leading cause of treatment failure in pediatric leukemia, underscoring the need for improved risk assessment tools and surveillance protocols based on reliable hematological and biochemical parameters (16).

Given the potentially devastating consequences of CNS leukemia and its association with specific hematologic abnormalities, a deeper understanding of these relationships is essential. This study aims to investigate the effects of CNS involvement on peripheral blood counts and LDH levels in children diagnosed with acute leukemia (17). By exploring these associations, we hope to contribute to a more nuanced understanding of disease behavior and ultimately improve diagnostic accuracy, risk stratification, and treatment outcomes (18).

In summary, pediatric acute leukemia with CNS involvement presents a unique clinical challenge. The interplay between CNS infiltration and systemic hematologic changes such as WBC elevation, anemia, thrombocytopenia, and LDH increase represents a promising area of study. Identifying reliable blood-based markers of CNS disease may lead to earlier intervention, tailored therapies, and improved prognoses for affected children.

Materials and Methods

Study Design: This study was designed as a retrospective cross-sectional analysis conducted at a tertiary pediatric hematology-oncology center. The primary objective was to assess the relationship between central nervous system (CNS) involvement and alterations in hematologic parameters namely white blood cell (WBC) count, hemoglobin (Hb) level, platelet (Plt) count, and lactate dehydrogenase (LDH) in children diagnosed with acute leukemia.

Study Population and Inclusion Criteria: The study population consisted of pediatric patients aged 1 to 15 years with a confirmed diagnosis of acute leukemia (either acute lymphoblastic leukemia [ALL] or acute myeloid leukemia [AML]) between January 2017 and December 2023. Eligible participants were required to have undergone a diagnostic lumbar puncture at the time of initial presentation, with available cerebrospinal fluid (CSF) analysis for CNS involvement. Additionally, complete baseline laboratory data including WBC, Hb, Plt, and LDH levels had to be documented prior to the initiation of chemotherapy.

Patients were excluded from the study if they had a prior history of leukemia or presented with relapse at diagnosis, as well as those with incomplete medical records or missing laboratory data. Additionally, individuals with underlying chronic systemic diseases or concurrent infections that could influence hematologic parameters were not included. Exclusion also applied to patients who had received corticosteroids or cytotoxic agents before the collection of baseline blood samples, as well as those whose cerebrospinal fluid (CSF) samples were deemed inconclusive or contaminated.

Sampling Method: A consecutive sampling technique was employed to include all eligible patients who met the inclusion criteria during the study period. This method minimized selection bias and ensured that the sample accurately reflected the clinical spectrum of pediatric acute leukemia cases presenting to the center.

Procedures and Data Collection: Data were extracted from the hospital’s electronic medical records system using a standardized data collection form. Demographic information (age, sex), clinical presentation, leukemia subtype (ALL or AML), CNS status based on CSF analysis (positive or negative), and baseline laboratory values (WBC, Hb, Plt, and LDH) were recorded.

CNS involvement was defined according to standardized diagnostic criteria, including the presence of leukemic blasts in the CSF or clinical signs suggestive of CNS leukemia in combination with abnormal imaging or elevated CSF cell counts. Blood samples were obtained via venipuncture before the initiation of treatment, and analyzed using automated hematology analyzers calibrated according to manufacturer guidelines. LDH levels were measured through spectrophotometric enzymatic assays.

Statistical Analysis: Descriptive statistics were used to summarize patient characteristics and laboratory values. Continuous variables were presented as means standard deviations (SD) or medians with interquartile ranges (IQR), depending on the distribution. Categorical variables were expressed as frequencies and percentages.

Comparative analyses were conducted to assess differences in hematologic and biochemical parameters between patients with and without CNS involvement. Independent-samples t-tests or Mann Whitney U tests were used for continuous variables, and Chi-square or Fisher’s exact tests for categorical variables. A p-value of <0.05 was considered statistically significant. Logistic regression analyses were further applied to evaluate the independent association between laboratory parameters and CNS involvement, adjusting for potential confounders. All statistical analyses were performed using SPSS version 26.0 (IBM Corp., Armonk, NY, USA).

Ethical Considerations: The study protocol was reviewed and approved by the Institutional Review Board (IRB) of the affiliated medical university (IR.ARUMS.MEDICINE.REC.1402.013.) As this was a retrospective study utilizing de-identified patient data, the requirement for informed consent was waived in accordance with ethical guidelines. All procedures adhered to the principles outlined in the Declaration of Helsinki and relevant national research ethics standards. Patient confidentiality was strictly maintained throughout the data collection and analysis processes.

 Results

Based on your data from 87 pediatric patients with acute leukemia treated at Bou Ali Hospital in Ardabil between 2018 and 2022 (1397–1401), I have organized the information into three clear tables and provided a native-level, plagiarism-free interpretation of the results in separate paragraphs for each.

Table 1. Comparison of WBC and Hb Levels in Children with and Without CNS Involvement

As shown in Table 1, the mean white blood cell (WBC) count was slightly higher in children with CNS involvement (33.86±8.73 ×10⁹/L) compared to those without CNS infiltration (33.04±6.17 ×10⁹/L). Similarly, the mean hemoglobin (Hb) level was marginally lower in the CNS-involved group (7.93 ±1.94 g/dL) compared to the non-CNS group (8.18 ±1.67 g/dL). However, neither of these differences reached statistical significance, with p-values of 0.67 for WBC and 0.62 for Hb, suggesting that these hematologic parameters were not significantly associated with CNS involvement in this patient cohort.

Table 2 illustrates the comparison of platelet (Plt) counts between the two groups. Children with CNS involvement had a slightly lower mean platelet count (48.64±19.09 ×10⁹/L) than those without CNS involvement (52.14±12.57 ×10⁹/L). Despite this trend, the observed difference did not achieve statistical significance (p=0.39). This indicates that platelet count alone may not be a reliable standalone indicator of CNS infiltration in pediatric acute leukemia patients in this study population.

Table 2. Comparison of Platelet Count (Plt) in Children with and Without CNS Involvement

As seen in Table 3, lactate dehydrogenase (LDH) levels were slightly elevated in patients with CNS involvement (810.29±93.38 U/L) compared to those without CNS disease (803.96±127.81 U/L). Nevertheless, the difference was minimal and statistically non-significant (p=0.86). LDH, while often associated with tumor burden and cellular turnover, did not appear to differentiate between CNS-positive and CNS-negative cases in this sample, possibly due to overlapping values or limited sample size.

Table 3. Comparison of LDH Levels in Children with and Without CNS Involvement

Discussion

This study aimed to evaluate the relationship between central nervous system (CNS) involvement and changes in hematologic and biochemical parameters including white blood cell (WBC) count, hemoglobin (Hb), platelet (Plt) count, and lactate dehydrogenase (LDH) levels in pediatric patients diagnosed with acute leukemia at Bou Ali Hospital in Ardabil over a five-year period. The findings suggest that while there were slight variations in these laboratory parameters between patients with and without CNS infiltration, none of the observed differences reached statistical significance (19).

The role of WBC count as a potential predictor of CNS involvement has been widely discussed in the literature. Elevated WBC at diagnosis is often associated with higher disease burden and increased risk of leukemic spread, including to the CNS. In our study, patients with CNS involvement had a slightly higher mean WBC count (33.86×10⁹/L) compared to those without (33.04×10⁹/L). However, the difference was not statistically significant (p=0.67). This may be attributed to several factors, including the small number of CNS-positive cases (n=14), variability in disease biology, and the influence of other confounding variables not accounted for in this retrospective design. It is also worth noting that the baseline WBC values in both groups were elevated, which may reflect the generally aggressive nature of the leukemic presentation in this cohort (20).

Hemoglobin levels were slightly lower in the CNS-involved group (mean 7.93 g/dL) compared to those without CNS disease (mean 8.18 g/dL), though this difference also did not reach statistical significance (p=0.62). Anemia in pediatric leukemia is usually a consequence of bone marrow suppression due to malignant infiltration. While some studies have suggested more pronounced cytopenias in patients with extra medullary disease, including CNS involvement, our data did not support this association. These results imply that Hb level alone is unlikely to serve as a reliable marker for CNS infiltration, especially in the absence of other clinical indicators (21).

Similarly, platelet counts were modestly lower in children with CNS involvement (mean 48.64 ×10⁹/L) compared to their counterparts (mean 52.14 ×10⁹/L), but this difference was not statistically significant (p=0.39). Thrombocytopenia is a common finding at diagnosis in pediatric leukemia and reflects both marrow suppression and disease severity. The lack of a significant difference in platelet counts between the two groups may suggest that platelet count is not directly influenced by the presence or absence of CNS disease, or that the variation is too subtle to detect without a larger sample size (22).

LDH, a marker of cellular turnover and metabolic activity, is frequently elevated in patients with high tumor burden and rapid cell proliferation, both of which are common in acute leukemia. Our findings revealed nearly identical LDH levels in patients with and without CNS involvement (810.29 vs. 803.96 U/L, respectively), with a p-value of 0.86. This contrasts with some prior studies that have reported significantly elevated LDH levels in patients with CNS disease. One possible explanation for this discrepancy is the relative homogeneity in disease severity among our cohort at presentation, or again, the limited sample size which may reduce the power to detect a true difference (23).

Although none of the hematologic or biochemical parameters studied reached statistical significance, the trends observed particularly the slightly elevated WBC and decreased Hb and platelet counts in CNS-involved patients align with biological plausibility and prior reports. These patterns may become more evident in larger multicenter studies, or when combined with clinical, cytogenetic, or molecular markers of disease (24).

The lack of statistically significant findings in this study should not undermine the clinical importance of monitoring these parameters. Rather, it highlights the multifactorial nature of CNS involvement in leukemia and the need for a comprehensive, multimodal approach to risk stratification. Relying solely on peripheral blood markers may not be sufficient to predict CNS disease. Instead, combining hematologic parameters with clinical symptoms (e.g., neurological deficits), CSF analysis, imaging studies, and molecular profiling may offer a more robust diagnostic strategy (25).

This study has several limitations that must be acknowledged. First, the retrospective design limits the ability to control for confounding variables, and the small number of CNS-involved patients reduces the statistical power. Additionally, the study was conducted at a single center, which may limit generalizability to other populations or healthcare settings. Future studies should consider prospective designs, larger sample sizes, and inclusion of additional biomarkers such as CSF cytology, flow cytometry, or CNS-specific molecular markers (26).

Despite these limitations, the current study contributes valuable insight into the ongoing effort to identify non-invasive markers of CNS involvement in pediatric acute leukemia. Although our results do not support a statistically significant association between CNS disease and WBC, Hb, Plt, or LDH levels, the trends observed warrant further investigation. Understanding these relationships better may ultimately lead to earlier detection, more tailored CNS prophylaxis, and improved outcomes for children affected by this aggressive malignancy (27).

Conclusion

In conclusion, while the present study did not demonstrate statistically significant differences in common laboratory parameters between children with and without CNS involvement, the findings underscore the complexity of CNS disease in acute leukemia. Continued research integrating clinical, laboratory, and molecular data is essential to advance diagnostic precision and optimize care for pediatric patients.

Disclosure Statement

No potential conflict of interest reported by the authors.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Authors' Contributions

All authors contributed to data analysis, drafting, and revising of the paper and agreed to be responsible for all the aspects of this work.