Monocyte-to-Lymphocyte Ratio as a Biomarker for Functional Status in Chronic Lymphocytic Leukemia: Implications for Prognosis and Treatment Strategies

MLR: A Potential New Biomarker in Chronic Lymphocytic Leukemia Management

August 22, 2025

A recently published study indicates that the monocyte-to-lymphocyte ratio (MLR) may offer important insights into the progression and activity of Chronic Lymphocytic Leukemia (CLL).The findings, announced this week, highlight MLR’s potential as a readily accessible biomarker for clinicians monitoring patients with this common blood cancer.

Understanding the Link Between Inflammation and CLL

Researchers have long recognized a connection between inflammation within the tumor microenvironment and the growth and advancement of CLL. Earlier studies demonstrated that individuals with CLL and reduced monocyte levels faced elevated risks of mortality, largely due to an increased susceptibility to infections. Though, the exact nature of this inflammatory connection remained unclear.

Current methods for evaluating inflammation rely on measuring inflammatory indicators in blood samples.Though, researchers propose that a more comprehensive analysis of immune cells circulating in the blood, specifically utilizing the MLR, could provide a more nuanced and informative assessment.

The Study’s Methodology and Key Findings

The investigation involved collecting peripheral blood samples from 54 patients newly diagnosed with CLL, alongside samples from 20 healthy individuals for comparison. Refined laboratory techniques, including multiparametric flow cytometry and fluorescence-activated cell sorting, were employed to analyze the samples.

The analysis revealed that CLL patients exhibited notably lower MLR values compared to their healthy counterparts (P < .0001). Furthermore, patients with more advanced stages of CLL (stage III or IV) demonstrated considerably higher MLR values than those with early-stage disease (P < .01). The study also found that patients exhibiting unfavorable clinical and laboratory markers-such as elevated levels of CD5+/CD19+ cells expressing ZAP-70 and CD38-also presented with higher MLR values.

MLR and Monocyte Subpopulations

Patients were categorized into MLR-high and MLR-low groups (13 and 41 participants, respectively). The MLR-high group displayed a higher proportion of intermediate monocytes and a lower percentage of classical and nonclassical monocytes. Notably, this group also exhibited altered functional characteristics within their monocyte populations. As an example, they showed reduced expression of TNF in nonclassical monocytes and increased expression of IL-10 in intermediate monocytes which suggested a correlation between immune cell function and disease progression.

Additionally,differences were observed in the expression of microRNAs (miR-106a,miR-150-5p,and miR-21-3p) between CLL patients and healthy controls. The investigators suggest these findings indicate that inflammatory conditions related to CLL perhaps influence monocyte subpopulation heterogeneity.

What Does This Mean For CLL Patients?

While acknowledging the study’s limitations, including its relatively small sample size and focus on newly diagnosed patients, the researchers conclude that MLR holds promise as a valuable tool for gaining deeper insights into the immune status of CLL patients.It could aid in refining risk assessments and tailoring treatment strategies.

Did you know? CLL affects more than 20,000 adults in the United States each year, according to the Leukemia & Lymphoma Society.

Characteristic	CLL Patients	Healthy Donors
Median MLR Value	0.04 (IQR 0.095-0.02)	0.265 (IQR 0.318-0.23)
MLR & Disease Stage	Higher in Stage III/IV	Lower in Stage 0
Monocyte Subtypes (MLR-High)	Increased Intermediate Monocytes	N/A

Pro Tip: Maintaining a healthy lifestyle, including a balanced diet and regular exercise, can support overall immune function, which is especially important for individuals with CLL.

What are your thoughts on the potential of MLR as a new biomarker for CLL? Do you believe that more personalized approaches to CLL treatment are necessary?

Chronic Lymphocytic Leukemia: A Deeper Look

CLL is a type of cancer of the blood and bone marrow characterized by the slow accumulation of abnormal lymphocytes. it frequently enough has no noticeable symptoms in its early stages and is often discovered during routine blood tests. Treatment options vary depending on the stage and progression of the disease and can range from watchful waiting to chemotherapy, immunotherapy, and targeted therapies. The American Cancer Society provides extensive resources on CLL, including detailed data on diagnosis, treatment, and support services: https://www.cancer.org/cancer/chronic-lymphocytic-leukemia.html

Frequently Asked Questions About MLR and CLL

• What is the monocyte-to-lymphocyte ratio (MLR)? It is a calculation based on the number of monocytes and lymphocytes in a blood sample, offering a potential indicator of immune system activity.
• How can MLR help with CLL diagnosis? While it is not a diagnostic tool, MLR can provide insights into the progression and activity of CLL.
• Is MLR a reliable predictor of CLL prognosis? The study suggests it correlates with disease stage and prognostic factors, but further research is needed to confirm its predictive value.
• What are the limitations of the MLR study? The study involved a limited number of patients and focused solely on those newly diagnosed with CLL.
• What are the next steps in researching MLR and CLL? Researchers plan to conduct larger studies with diverse patient populations to validate these findings and explore its clinical applications.
• Can lifestyle changes impact the MLR in CLL patients? While more research is needed, maintaining a healthy lifestyle is beneficial for overall immune health.

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How does the MLR correlate with treatment response to BTK and BCL-2 inhibitors in CLL patients?

Understanding the Monocyte-to-Lymphocyte Ratio (MLR)

The monocyte-to-lymphocyte ratio (MLR), a readily available parameter derived from a complete blood count (CBC), is increasingly recognized as a valuable biomarker in hematological malignancies, especially in Chronic lymphocytic Leukemia (CLL). Traditionally, CLL prognosis relied heavily on staging systems like Rai and Binet, alongside cytogenetic abnormalities.However, thes methods don’t always fully capture the dynamic interplay between the disease and the patient’s immune system. The MLR offers a cost-effective and easily obtainable assessment of this immune status, providing insights into disease progression, treatment response, and overall survival. It reflects the balance between systemic inflammation (monocytes) and immune competence (lymphocytes). Elevated MLR frequently enough indicates a pro-inflammatory state and impaired immune function, both frequently observed in advanced CLL.

CLL and Immune Dysfunction: The Role of Monocytes and Lymphocytes

chronic Lymphocytic Leukemia is characterized by the accumulation of monoclonal B lymphocytes. However, the disease’s impact extends far beyond these malignant cells. CLL disrupts normal immune function in several ways:

Lymphopenia: A hallmark of CLL, the progressive depletion of normal lymphocytes weakens the body’s ability to fight infection.

Monocyte Activation: CLL cells can stimulate monocytes, leading to increased production of pro-inflammatory cytokines.

T Cell Dysfunction: CLL affects T cell function, further compromising the immune response.

Impaired Antibody Production: B cell dysfunction leads to hypogammaglobulinemia, increasing susceptibility to infections.

the MLR, therefore, serves as an integrated measure of these immune alterations. A higher MLR suggests a greater degree of immune dysregulation and a potentially more aggressive disease course. Terms like CLL immune escape and CLL microenvironment are directly related to the changes reflected in the MLR.

MLR and Prognostic Stratification in CLL

Several studies have demonstrated a strong correlation between elevated MLR and adverse prognostic factors in CLL.

Advanced Stage Disease: Patients with higher MLR values tend to present with more advanced stages of CLL (Rai III/IV or Binet C).

Unmutated IGHV Gene Status: IGHV unmutated CLL, generally associated with a more aggressive clinical course, frequently enough exhibits a higher MLR. IGHV mutation status remains a critical prognostic indicator.

Complex Karyotype: Patients with complex karyotypes, indicating genomic instability, frequently have elevated MLR levels.

Shorter Time to First Treatment (TTFT): Higher MLR is associated with a shorter time until the need for CLL-specific therapy.

Overall Survival (OS): Multiple studies have shown that a high MLR is an independent predictor of shorter overall survival in CLL patients. CLL survival rates are considerably impacted by MLR.

Specifically, an MLR cut-off of >2.0 has been frequently used in research to identify patients at higher risk. Though, optimal cut-off values may vary depending on the patient population and laboratory standards.

MLR as a Predictor of Treatment Response

The MLR isn’t just useful for initial prognosis; it also provides valuable details regarding treatment response.

Chemoimmunotherapy: In patients undergoing chemoimmunotherapy (e.g., fludarabine, cyclophosphamide, and rituximab – FCR), a decrease in MLR following treatment is associated with a more favorable response and longer progression-free survival (PFS).

Bruton’s Tyrosine Kinase (BTK) Inhibitors: BTK inhibitors (e.g.,ibrutinib,acalabrutinib) are now a mainstay of CLL treatment. A rapid and sustained reduction in MLR following BTK inhibitor therapy is a strong predictor of clinical benefit. Monitoring MLR during BTK inhibitor therapy is becoming standard practice.

BCL-2 Inhibitors: similar to BTK inhibitors, a decrease in MLR with BCL-2 inhibitor treatment (e.g., venetoclax) correlates with improved outcomes.

* Minimal Residual Disease (MRD): MLR changes often parallel MRD status. patients achieving MRD negativity (undetectable CLL cells) typically demonstrate a meaningful reduction in MLR. CLL MRD assessment and MLR are complementary tools.

Clinical Applications and Monitoring Strategies

Integrating MLR into CLL management offers several practical benefits:

1. Risk Stratification: MLR can help identify patients who may benefit from more aggressive treatment strategies or closer monitoring.
2. Treatment selection: MLR can inform