Current NCCN Recommendations for Classification and Risk Symptoms in SLL/CLL

Classification of SLL

The classification of small lymphocytic lymphoma typically uses the Lugano modification of the Ann Arbor staging system:

• Stage I with involvement of 1 node or group of adjacent nodes. This also includes a single extranodal lesion without node involvement.
• Stage II with involvement of ≥ 2 nodal groups on the same side of the diaphragm. Stage II with a bulky disease is evaluated separately. 
• Stage III with involvement of nodes on both sides of the diaphragm, or nodes above the diaphragm with concurrent spleen involvement.
• Stage IV indicates further involvement outside of nodes, not in their proximity.

Stage III and IV represent advanced stages of the disease. The spleen, tonsils, and Waldeyer's ring are considered lymphatic tissue. PET/CT examination is clearly preferred for diagnosing the extent of the disease.

Classification of CLL

The Rai staging system is most commonly used for chronic lymphocytic leukemia:

• Stage 0 with lymphocytosis, lymphocytes in the blood > 5 × 10⁹/l, clonal B lymphocytes and/or > 40% lymphocytes in the bone marrow. Modified risk status assessed as low.
• Stage I includes stage 0 with enlarged nodes. Modified risk status assessed as intermediate.
• Stage II includes stages 0 and I with splenomegaly, hepatomegaly, or both. Modified risk status assessed as intermediate.
• Stage III includes stages 0–II with hemoglobin (Hgb) < 110 g/l or hematocrit < 33%, with immune-mediated cytopenia not meeting the criteria for this stage definition. Modified risk status assessed as high.
• Stage IV includes stages 0–III with platelet count < 100 × 10⁹/l. Modified risk status assessed as high.

Alternatively, the Binet staging system (stage A–C based on hemoglobin levels, platelet count, and the number of enlarged node groups) may be used. 

Stage of Disease and Associated Risk Factors Affecting Treatment

In SLL Lugano Stage I, local radiotherapy at a dose of 24–30 Gy, delivered in fractions (usually 1.5–2 Gy), may be therapeutically indicated.

In the observation of low-stage SLL, it is always necessary to monitor for potential signs of disease progression and risk factors that may require the initiation or modification of treatment. These signs should also be assessed in the case of a CLL diagnosis or more advanced stages of SLL. Warning signs primarily include:

• Significant symptoms associated with the disease:
  • severe fatigue
  • night sweats
  • weight loss of ≥ 10% in the preceding 6 months (without the patient's intention to lose weight)
  • elevated temperatures without signs of infection
• Progressive bulky disease: spleen > 6 cm below the rib arch, nodal mass > 10 cm.
• Progressive anemia.
• Progressive thrombocytopenia, where a platelet count > 100 × 10⁹/l is typically not associated with clinically significant risk.
• Autoimmune cytopenia refractory to corticosteroid treatment.

For deciding on the initiation of treatment, it is also significant to assess the presence of any organ involvement and the potential suitability for including the patient in a clinical trial. Furthermore, the absolute lymphocyte count alone is not an indication for treatment if leukostasis is not present, which is very rare in CLL.

In the case of progressive disease, histological transformation, or histological progression of CLL/SLL, the next treatment steps must also be carefully assessed.

In CLL-associated cytopenia, for some patients with mild stable cytopenia (ANC < 1 × 10⁹/l; Hgb < 110 g/l or platelet count < 100 × 10⁹/l), observation alone may be chosen.

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Source: Wierda W. G., Brown J., Abramson J. S. et al. NCCN guidelines: Chronic lymphocytic leukemia/small lymphocytic lymphoma. Version 1.2023. National Comprehensive Cancer Network, 2022 Aug 30. Available at: www.nccn.org/professionals/physician_gls/pdf/cll.pdf