Immune disorder and infection risk in patients with early-stage CLL

This paper studied hypogammaglobulinemia, an immune disorder, in patients with early-stage chronic lymphocytic leukemia (CLL). Researchers reported that low antibody levels at diagnosis did not increase the risk of a serious infection. However, patients with more aggressive disease are more likely to develop a late hypogammaglobulinemia. Late hypogammaglobulinemia increased the risk of a serious infection.

Standard therapy for CLL usually involves a combination of chemotherapies and immunotherapies. Long courses of treatment are typically needed. This prolonged treatment can weaken a patient’s immune response. Over time, many CLL patients will develop a condition called hypogammaglobulinemia (HGG). This is an immune disorder where the body’s antibody levels are severely reduced, which increases the risk of serious infections. HGG cannot usually be reversed even with response to CLL therapy. HGG is usually observed in patients with advanced and previously treated disease. It has also been recorded in patients with early-stage CLL. However, more studies are needed on predictive factors of HGG and the infection risk in patients with early-stage CLL. 

The records of 899 early-stage CLL patients were analyzed. Antibody levels (called immunoglobulins) were measured in all patient at diagnosis. Other disease characteristics and the presence of genetic abnormalities (making CLL harder to treat) were also recorded. Incidences of HGG were followed over an average period of 6.9 years.

Before receiving first-line therapy for CLL, 12.9% of patients experienced at least one serious infection that needed treatment or hospitalization. Infections of the respiratory tract were the most common infections (6.8%). At 5 years, 92.3% of patients were estimated to be infection-free.

Low levels of the immunoglobulin G at diagnosis were seen in 19.9% of patients. 10.4% of patients showed low levels of the immunoglobulin M or immunoglobulin A at diagnosis. Immunoglobulin levels at diagnosis did not significantly increase the risk of infection. The only independent risk factors for infection were the presence of genetic abnormalities. These included deletion 11q, deletion 17p, and unmutated IGHV gene.

An additional 19.9% of patients developed HGG during the study period. The average time between diagnosis and HGG was 36 months. A significantly higher rate of serious infections was recorded in patients who developed a late HGG (15.1%) compared to patients with steadily normal antibody levels (10.6%). Increased stage disease (Rai stage I or II) and unmutated IGHV gene increased the risk of a late HGG.

The 5-year overall survival rate (proportion who have not died from any cause since treatment) was 88.6%. Immunoglobulin levels at diagnosis had no significant effect on survival. Older age, men, Rai stage I or II, an enlarged spleen, and increased beta-2 microglobulin in the blood (a tumor marker) were all found to impact survival.

This study concluded that early-stage CLL patients with clinical characteristics indicating more aggressive disease are more likely to develop a late HGG. These patients require close clinical monitoring.

Further studies are needed to confirm these results.