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

Sameer A. Parikh, Jose F. Leis, Kari G. Chaffee, Timothy G. Call, Curtis A. Hanson, Wei Ding, Asher A. Chanan-Khan, Deborah Bowen, Michael Conte, Susan Schwager, Susan L. Slager, Daniel L. Van Dyke, Diane F. Jelinek, Neil E. Kay, Tait D. Shanafelt

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2883-2891
Number of pages9
Issue number17
StatePublished - Sep 1 2015


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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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