Hypogammaglobulinemia in newly diagnosed chronic lymphocytic leukemia: Natural history, clinical correlates, and outcomes

• Published in: Cancer Vol. 121; no. 17; pp. 2883 - 2891
• Main Authors: Parikh, Sameer A., Leis, Jose F., Chaffee, Kari G., Call, Timothy G., Hanson, Curtis A., Ding, Wei, Chanan‐Khan, Asher A., Bowen, Deborah, Conte, Michael, Schwager, Susan, Slager, Susan L., Van Dyke, Daniel L., Jelinek, Diane F., Kay, Neil E., Shanafelt, Tait D.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.09.2015
• Subjects: Adult; Agammaglobulinemia - diagnosis; Agammaglobulinemia - mortality; Agammaglobulinemia - therapy; Aged; Aged, 80 and over; Cancer; CD49d antigen; Chronic lymphocytic leukemia; Diagnosis; Female; Humans; Hypogammaglobulinemia; immune dysregulation; Immunoglobulin G; Immunoglobulin G - blood; Kaplan-Meier Estimate; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - blood; Leukemia, Lymphocytic, Chronic, B-Cell - diagnosis; Leukemia, Lymphocytic, Chronic, B-Cell - mortality; Leukemia, Lymphocytic, Chronic, B-Cell - therapy; Lymphatic leukemia; Male; Middle Aged; Multivariate Analysis; Oncology; outcomes; Patients; prognostic markers; Proportional Hazards Models; Retrospective Studies; Survival; Treatment Outcome; chronic lymphocytic leukemia; hypogammaglobulinemia; prognostic markers; outcomes; immune dysregulation
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.29438

BACKGROUND Although hypogammaglobulinemia is a well recognized complication in patients with chronic lymphocytic leukemia (CLL), its prevalence at the time of CLL diagnosis, and association with novel prognostic markers and clinical outcome is not well understood. METHODS All patients at the Mayo Clinic between January 1999 and July 2013 who had newly diagnosed CLL and had a baseline assessment of serum immunoglobulin G (IgG) were included. The relation between hypogammaglobulinemia at diagnosis and the novel prognostic parameters time to first treatment (TFT) and overall survival (OS) were evaluated. RESULTS Of 1485 patients who met the eligibility criteria, 382 (26%) had hypogammaglobulinemia (median IgG, 624 mg/dL), whereas the remaining 1103 patients (74%) had normal serum IgG levels (median IgG, 1040 mg/dL). Patients who had hypogammaglobulinemia at diagnosis were more likely to have advanced Rai stage (III‐IV; P = .001) and higher expression of CD49d (P < .001) compared with patients who had normal IgG levels. Although the median TFT for patients who had hypogammaglobulinemia was shorter compared with that for patients who had normal IgG levels (3.8 years vs 7.4 years; P < .001), on multivariable analysis, there was no difference in OS between these 2 groups (12.8 years vs 11.3 years, respectively; P = .73). Of 1103 patients who had CLL with normal IgG levels at diagnosis and who did not receive CLL therapy, the risk of acquired hypogammaglobulinemia was 11% at 5 years and 23% at 10 years. CONCLUSIONS Hypogammaglobulinemia is present in 25% of patients with newly diagnosed CLL. Approximately 25% of patients who have CLL with normal IgG levels at diagnosis will subsequently develop hypogammaglobulinemia on long‐term follow‐up. The presence of hypogammaglobulinemia does not appear to impact overall survival. Cancer 2015;121:2883–2891. © 2015 American Cancer Society. This large, retrospective cohort study of approximately 1500 patients with chronic lymphocytic leukemia (CLL) indicates that approximately 25% of patients with CLL have hypogammaglobulinemia at the time of their initial diagnosis; and, among those who have normal serum immunoglobulin G levels at diagnosis, approximately 25% develop hypogammaglobulinemia over the next 10 years without the receipt of CLL therapy. Although the presence of hypogammaglobulinemia at initial diagnosis predicts the time to first CLL therapy, it does not have an impact on overall survival.