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 D Ding, Asher A Chanan Khan, Deborah Bowen, Michael Conte, Susan Schwager, Susan L Slager, Daniel L. Van Dyke, Diane F Jelinek, Neil Elliot Kay, Tait D. Shanafelt

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalCancer
DOIs
StateAccepted/In press - 2015

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Agammaglobulinemia
B-Cell Chronic Lymphocytic Leukemia
Natural History
Immunoglobulin G
Survival
Common Variable Immunodeficiency
Serum
Therapeutics
Biomarkers

Keywords

  • Chronic lymphocytic leukemia
  • Hypogammaglobulinemia
  • Immune dysregulation
  • Outcomes
  • Prognostic markers

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Hypogammaglobulinemia in newly diagnosed chronic lymphocytic leukemia : Natural history, clinical correlates, and outcomes. / Parikh, Sameer A; Leis, Jose F.; Chaffee, Kari G.; Call, Timothy G.; Hanson, Curtis A.; Ding, Wei D; Chanan Khan, Asher A; Bowen, Deborah; Conte, Michael; Schwager, Susan; Slager, Susan L; Van Dyke, Daniel L.; Jelinek, Diane F; Kay, Neil Elliot; Shanafelt, Tait D.

In: Cancer, 2015.

Research output: Contribution to journalArticle

Parikh, Sameer A ; Leis, Jose F. ; Chaffee, Kari G. ; Call, Timothy G. ; Hanson, Curtis A. ; Ding, Wei D ; Chanan Khan, Asher A ; Bowen, Deborah ; Conte, Michael ; Schwager, Susan ; Slager, Susan L ; Van Dyke, Daniel L. ; Jelinek, Diane F ; Kay, Neil Elliot ; Shanafelt, Tait D. / Hypogammaglobulinemia in newly diagnosed chronic lymphocytic leukemia : Natural history, clinical correlates, and outcomes. In: Cancer. 2015.
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title = "Hypogammaglobulinemia in newly diagnosed chronic lymphocytic leukemia: Natural history, clinical correlates, and outcomes",
abstract = "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.",
keywords = "Chronic lymphocytic leukemia, Hypogammaglobulinemia, Immune dysregulation, Outcomes, Prognostic markers",
author = "Parikh, {Sameer A} and Leis, {Jose F.} and Chaffee, {Kari G.} and Call, {Timothy G.} and Hanson, {Curtis A.} and Ding, {Wei D} and {Chanan Khan}, {Asher A} and Deborah Bowen and Michael Conte and Susan Schwager and Slager, {Susan L} and {Van Dyke}, {Daniel L.} and Jelinek, {Diane F} and Kay, {Neil Elliot} and Shanafelt, {Tait D.}",
year = "2015",
doi = "10.1002/cncr.29438",
language = "English (US)",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",

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TY - JOUR

T1 - Hypogammaglobulinemia in newly diagnosed chronic lymphocytic leukemia

T2 - Natural history, clinical correlates, and outcomes

AU - Parikh, Sameer A

AU - Leis, Jose F.

AU - Chaffee, Kari G.

AU - Call, Timothy G.

AU - Hanson, Curtis A.

AU - Ding, Wei D

AU - Chanan Khan, Asher A

AU - Bowen, Deborah

AU - Conte, Michael

AU - Schwager, Susan

AU - Slager, Susan L

AU - Van Dyke, Daniel L.

AU - Jelinek, Diane F

AU - Kay, Neil Elliot

AU - Shanafelt, Tait D.

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - Chronic lymphocytic leukemia

KW - Hypogammaglobulinemia

KW - Immune dysregulation

KW - Outcomes

KW - Prognostic markers

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U2 - 10.1002/cncr.29438

DO - 10.1002/cncr.29438

M3 - Article

JO - Cancer

JF - Cancer

SN - 0008-543X

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