What are the risk factors for Nodular Lymphocyte-Predominant (NLP) Non-Hodgkin Lymphoma (NHL)?

Risk Factors for Nodular Lymphocyte Predominant Non-Hodgkin Lymphoma

The primary risk factors for Nodular Lymphocyte-Predominant (NLP) Non-Hodgkin Lymphoma include age over 45 years, male gender, advanced disease stage (III-IV), hemoglobin <10.5 g/dL, and splenic involvement. 1

Epidemiological Risk Factors

• Age: NLPHL typically affects adults in their third to fifth decades of life 2

  • Patients with age ≥45 years have significantly worse prognosis 1
  • Median age at diagnosis is approximately 37 years 1

• Gender: Strong male predominance

  • Males are affected more frequently than females 2
  • This gender disparity is more pronounced in NLPHL than in classical Hodgkin lymphoma

• Disease Presentation:

  • Most patients (>70%) present with early-stage disease (stages I-II) 3, 1
  • B symptoms (fever, night sweats, weight loss) are rare, occurring in only 4-10% of NLPHL patients 3, 1
  • Typically presents with painless, peripheral lymphadenopathy

Biological and Prognostic Risk Factors

The recently developed Lymphocyte-Predominant International Prognostic Score (LP-IPS) identifies four key risk factors that predict worse outcomes 1:

1. Age ≥45 years
2. Advanced stage disease (stages III-IV)
3. Hemoglobin <10.5 g/dL
4. Splenic involvement

Each factor contributes one point to the LP-IPS, with higher scores associated with:

• Worse progression-free survival
• Worse overall survival
• Increased risk of transformation to aggressive lymphoma
• Higher lymphoma-specific death rate

Risk of Disease Transformation

NLPHL carries an inherent risk of transformation to aggressive non-Hodgkin lymphoma, particularly diffuse large B-cell lymphoma (DLBCL):

• Transformation rate is approximately 4.8% at 10 years 1
• Patients with splenic involvement have higher transformation risk 4
• Specific immunoarchitectural pattern (IAP E) is associated with 1.81-fold higher risk of transformation 1

Clinical Course and Prognosis

Despite these risk factors, NLPHL generally has an excellent prognosis:

• 10-year progression-free survival: 70.8% 1
• 10-year overall survival: 91.6% 1
• Lymphoma-specific death rate at 10 years: only 3.3% 1

Important Clinical Considerations

• NLPHL is distinct from classical Hodgkin lymphoma both clinically and biologically
• The malignant LP cells express CD20 but lack CD15 and CD30 expression, unlike classical Hodgkin lymphoma 2
• Despite frequent relapses (approximately 10% of patients), the disease has an excellent overall survival 3
• All relapses and transformations are generally salvageable with appropriate therapy 3

Understanding these risk factors is essential for risk stratification and treatment planning, particularly as emerging evidence suggests that patients with low LP-IPS scores (<2) may be candidates for de-escalated therapy 1.