Ask the Expert: The Difference Between CLL Stage and SLL Stage

Question

What is the difference between CLL stage (Rai or Binet) and SLL stage (Ann Arbor)? Why does the same disease have two different staging systems?

Answer

Dr. Richard Furman, M.D.
Dr. Richard Furman, M.D.

Dr. Richard Furman writes: The purpose of a staging system is to help clinicians better determine prognosis and plan treatment for a patient’s disease. Although chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are the same disease, they were not recognized as the same disease until 1994. Since then they have been combined into one entity, CLL/SLL.

For historical reasons, CLL was staged based upon the Rai or Binet scheme (see below) and SLL was staged using the Ann Arbor lymphoma staging scheme (see below). Today most CLL specialists use the Rai stage because it is more clinically helpful. Using the Ann Arbor classification to stage SLL is problematic in scenarios where the disease has spread to the bone marrow. A person with SLL in their lymph nodes and bone marrow would immediately be characterized as an Ann Arbor stage IV, but their prognosis and treatment plan would be far better indicated as measured by the Rai stage I. Therefore the Rai stage, even without lymphocytosis, provides better prognostic and therapeutic information for a physician to treat their patient.

Rai Stages

0: lymphocytosis (an increase in number of lymphocytes in the blood).

I: Lymphocytosis + lymphadenopathy, (enlarged lymph nodes).

II: Lymphocytosis + splenomegaly (enlargement of the spleen) +/- lymphadenopathy

III: Lymphocytosis + anemia (decrease in red blood cells) +/- splenomegaly +/- lymphadenopathy

IV: Lymphocytosis + thrombocytopenia (decrease in platelets) +/- anemia +/- splenomegaly +/- lymphadenopathy

Ann Arbor Stages

I: Disease found in one group of lymph node

II: Disease found in two or more groups of lymph nodes on the same side of the diaphragm.

III: Disease found in two or more groups lymph nodes on both sides of the diaphragm.

IV: Extranodal disease (found outside of the lymph nodes), including bone marrow, liver, or other organs)

Note: if only one isolated area or organ involvement is present, then it would be a stage I, except for bone marrow.

Ibrutinib Granted Third Breakthrough Status for Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL)

On April 8, the FDA granted a third Breakthrough Therapy Designation for the investigational agent ibrutinib. Previously, receiving breakthrough status for the treatment of patients with Waldenström’s macroglobulinemia and mantle cell lymphoma, the drug has now achieved breakthrough status as a monotherapy for the treatment of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) in patients with deletion of the short arm of chromosome 17 (deletion 17p). This is an especially important development as CLL and SLL affected carriers of the deletion of chromosome 17 mutation are prone to poor prognoses, often due to their poor responses to chemoimmunotherapy.

Ibrutinib, an oral drug designed to specifically target an enzyme called Bruton’s tyrosine kinase (BTK), has demonstrated promising activity in multiple phase 1 and 2 clinical trials performed at Weill Cornell Medical College and around the world. As one of the leading institutions in the study of ibrutinib since its first testing 3 years ago, Weill Cornell is uniquely positioned in its experience with ibrutinib.

Currently, there are ongoing ibrutinib clinical trials at the Weill Cornell Lymphoma Program open to patients with CLL and SLL. Additional clinical trials for Waldenström’s macroglobulinemia and mantle cell lymphoma with ibrutinib are ongoing.

Please stay updated with our clinical trials listing for forthcoming trials involving ibrutinib and the Cornell Lymphoma Program website for further clinical research updates.