Does Hypogammaglobulinemia at Diagosis Effects Survival and Infection Risk in Chronic Lymphocytic Leukemia (CLL)?

Background: CLL is the most common leukemia in Western World. Hypogammaglobulinemia is the most common immune deficiency detected in CLL. Patients with CLL have increased risk of recurrent infections. Despite hypogammaglobulinemia reported as a cause of both infections and morbidity, controversy exists in its role.

Aim: In the present study, we have evaluated the impact of hypogammaglobulinemia at diagnosis on survival and infection risk in CLL.

Patients and Mathods: We have included 75 CLL patients diagnosed between 2000 and 2014 with B lymphocyte count >5000mm3, CD5, CD19, CD30, CD 23, CD79b positivity and surface Ig light chain restriction in flow cytometry at Ankara University School of Medicine Department of Hematology. The diagnosis and treatment criterias were depended on IWCLL 2008. The patient's performance status was evaluated by physician. If levels were considered decreased when values were below the normal ranges, defined as IgG 6.1-14.9 g/L, IgA 0.8-4.9 g/L and IgM 0.41-2.2 g/L. Overall survival (OS) was calculated by Kaplan-Meier method.

Results: The median age at diagnosis was 59 (range, 32-85). 47 patients (63%) were male. The frequencies of RAI staging from 0 to 4 were as follows; 17%, 13%, 25%, 13%, 32%. The ECOG performance status at diagnosis were stage 1 in 81%, stage 2 in %16, stage 3 in %3 of patients. FISH abnormality was detected in 19 patients (25%), del 13q was the most common. 39 patients (52%) (25 fit, 12 unfit, 2 unknown) received treatment. Fit patients got Rituximab-Fludarabine-Cyclophosphomide (R-FC) in first line whereas RFClite was preferred in unfit patients. 37 patients (49%) had any hypogammaglobulinemia at diagnosis; low IgG in 7 (9%), low IgM in 28 (37%), low IgA in 18 (24%) patients. During first year after diagnosis 26 patients (35%) had moderate to severe infections. Twenty five patients (68%) received intravenous immunoglobulin (IVIG) after diagnosis of hypogamaglobulinemia. No significant associations were found with Ig levels and infections. Six patients died during follow-up. 5-year OS in patients with normal and decreased gammaglobulin were 90% vs 86% (P=0.72). There were no survival advantage detected in low IgG, IgM, IgA subgroup analysis.

Conclusion: Hypogammaglobulinemia is considered predictive risk of infections. However we have not detected any significant increase of infections or decrease of survival in our cohort. Most of patients with hypogammaglobulinemia received IVIG after diagnosis which would effect our results.