Hypogammaglobulinemia in newly diagnosed chronic lymphocytic leukemia: Natural history, clinical correlates, and outcomes.
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.
Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
Sameer A
SA
Parikh
Department of Hematology and Oncology, Mayo Clinic, Phoenix, Arizona.
Jose F
JF
Leis
Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
Kari G
KG
Chaffee
Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
Timothy G
TG
Call
Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
Curtis A
CA
Hanson
Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
Wei
W
Ding
Division of Hematology and Oncology, Mayo Clinic, Jacksonville, Florida.
Asher A
AA
Chanan-Khan
Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
Deborah
D
Bowen
Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
Michael
M
Conte
Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
Susan
S
Schwager
Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
Susan L
SL
Slager
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
Daniel L
DL
Van Dyke
Department of Immunology, Mayo Clinic, Rochester, Minnesota.
Diane F
DF
Jelinek
Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
Neil E
NE
Kay
Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
Tait D
TD
Shanafelt
D000328:Adult; D000361:Agammaglobulinemia / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016896:Treatment Outcome
D007074:Immunoglobulin G
chronic lymphocytic leukemia; hypogammaglobulinemia; immune dysregulation; outcomes; prognostic markers