CLL INTRODUCTION: Immunology

Patients with chronic lymphocytic leukemia develop unique problems affecting their immune system and immune function which are not seen in other leukemias or lymphomas. As the CLL progresses, even previously untreated patients develop progressively lower normal antibody levels, which places them at increased risk for infection, particularly pneumonia and skin infections.

Interestingly, as the disease is developing, the number of T cells, (an important cell of the immune system,) increases. However, these T cells do not function normally. In fact, they are not able to effectively mount an immune reaction against viruses or other infectious agents and have significant difficulties communicating with other cells of the immune system. This results in reactivation of viruses such as Herpes zoster which causes shingles, and an inability to fight other viral infections. Also, this limits the patient's ability to have a protective response with vaccination. Patients who have received treatment for their leukemia have additional problems associated with their immune system and unfortunately treatment and achieving complete remission does not usually reverse existing immune defects. Although chemotherapy is effective at eliminating the leukemia, it also depletes normal immune cells, particularly T cells. This further suppresses the immunity of the patients, placing them at increased risk for infection for a period of months.Additionally, treatment is sometimes associated with a decrease in antibody levels, further adding to their risk for infection.

Immune dysregulation in both previously untreated patients and previously treated patients can also manifest as development of autoimmune diseases such autoimmune destruction of normal red cells and platelets, known as autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia purpura (ITP), respectively. These disorders contribute significantly to patient morbidity and can also lead to mortality.

The primary goals of current research in the immunology of patients with CLL are to understand the mechanisms of the disordered immunity. Work is ongoing to develop methods to reestablish the immune system and immune function. One method is to use the patient's own expanded and activated T cells. Additional efforts are ongoing to develop vaccine strategies to direct the immune system to react against a patient's own leukemia and thereby develop treatment strategies to utilize the immune system to eliminate disease. Finally, patients with CLL have distinct and unique immunologic disorders and defects. By correcting these defects, both the morbidity and mortality of CLL patients could be greatly improved. Therefore, there is an urgent need for continued research in this area.

The CLL cells inhibit B-cells and T-cells which play an important role in immune response. CLL cells are not able to effectively mount an immune reaction against viruses or other infectious agents. Chemotherapy further depletes normal immune cells. CLL cells produce rogue antibodies that may attack normal blood cells.