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Cancer. 2015 Sep 1;121(17):2883-91. doi: 10.1002/cncr.29438. Epub 2015 Apr 30.

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

Author information

Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
Department of Hematology and Oncology, Mayo Clinic, Phoenix, Arizona.
Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
Division of Hematology and Oncology, Mayo Clinic, Jacksonville, Florida.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
Department of Immunology, Mayo Clinic, Rochester, Minnesota.



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.


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.


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.


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.


chronic lymphocytic leukemia; hypogammaglobulinemia; immune dysregulation; outcomes; prognostic markers

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