Dataset Information

Prevalence and the impact of hypogammaglobulinemia in newly diagnosed chronic lymphocytic lymphoma patients.

ABSTRACT:

Objective

To examine the prevalence of hypogammaglobulinemia in chronic lymphocytic lymphoma (CLL) patients and to test the hypothesis that patients with hypogammaglobulinemia have a distinct clinical profile and outcome.

Methods

Immunoglobulin levels (IgA, IgG, IgM, IgE) were measured in newly diagnosed, treatment naïve banked samples of 150 patients with CLL followed prospectively for outcomes. Cox regression models were used to assess the effects of clinical variables on overall survival (OS).

Results

The median age of the selected CLL cohort was 64 years with a male predominance; 96.2% of the patients were white. Fifty-nine deaths occurred during a median follow up of 6.8 years. Hypogammaglobulinemia in CLL was common in our cohort with 88 (58.7%, 95% CI: 50.4-66.6%) patients having a measurable isotype deficiency. The most common Ig deficiency was IgM (44.0%). IgA deficiency or low IgE was associated with higher Rai stages as well as with higher white blood cell counts at presentation. Any immunoglobulin deficiency was not associated with overall survival.

Conclusion

A significant proportion of treatment-naïve CLL patients had underlying Ig deficiencies - both in isolation and in isotype combinations. Although a deficiency of IgA or IgE was associated with more severe disease at presentation, the impact of this association was mild.

SUBMITTER: Singh N

PROVIDER: S-EPMC9176078 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Prevalence and the impact of hypogammaglobulinemia in newly diagnosed chronic lymphocytic lymphoma patients.

Singh Namrata N Mott Sarah L SL Sutamtewagul Grerk G McCarthy Ashley A Slager Susan L SL Cerhan James R JR Ballas Zuhair Z Link Brian K BK

EJHaem 20200901 2

<h4>Objective</h4>To examine the prevalence of hypogammaglobulinemia in chronic lymphocytic lymphoma (CLL) patients and to test the hypothesis that patients with hypogammaglobulinemia have a distinct clinical profile and outcome.<h4>Methods</h4>Immunoglobulin levels (IgA, IgG, IgM, IgE) were measured in newly diagnosed, treatment naïve banked samples of 150 patients with CLL followed prospectively for outcomes. Cox regression models were used to assess the effects of clinical variables on overal ...[more]

PMID: 35845010

Similar Datasets

Project description:Key Points • DTI is strongly associated with adverse clinical factors and inferior survival outcomes in patients with newly diagnosed MCL.• DTI should be reported in all patients newly diagnosed with MCL enrolling in clinical trials; steps must be taken to avoid selection bias. Visual Abstract Abstract The prognostic relevance of diagnosis to treatment interval (DTI) in patients with newly diagnosed mantle cell lymphoma (MCL) is unknown. Hence, we sought to evaluate the impact of DTI on outcomes in MCL using 3 large datasets (1) the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource, (2) patients enrolled in the ALL Age Asthma Cohort/CALGB 50403, and (3) a multisitecohort of patients with MCL. Patients were a priori divided into 2 groups, 0 to 14 days (short DTI) and 15 to 60 days (long DTI). The patients in whom observation was deemed appropriate were excluded. One thousand ninety-seven patients newly diagnosed with MCL and available DTI were included in the study. The majority (73%) had long DTI (n=797). Patients with short DTI had worse eastern cooperative oncology group performance status (ECOG PS ≥2), higher lactate dehydrogenase, bone marrow involvement, more frequent B symptoms, higher MCL International Prognostic Index (MIPI ≥6.2), and were less likely to receive intensive induction therapy than long DTI group. The median progression-free survival (2.5 years vs 4.8 years, p<0.0001) and overall survival (7.8 years vs. 11.8 years, p<0.0001) were significantly inferior in the short DTI group than the long DTI cohort and remained significant for progression-free survival and overall survival in multivariable analysis. We show that the DTI is an important prognostic factor in patients newly diagnosed with MCL and is strongly associated with adverse clinical factors and poor outcomes. DTI should be reported in all the patients newly diagnosed with MCL who are enrolling in clinical trials and steps must be taken to ensure selection bias is avoided.

Project description:Chronic lymphocytic leukemia (CLL) is characterized by progressive hypogammaglobulinemia predisposing affected patients to a variety of infectious diseases but paradoxically not to cytomegalovirus (CMV) disease. Moreover, we found reactivity of a panel of CLL recombinant antibodies (CLL-rAbs) encoded by a germ-line allele with a single CMV protein, pUL32, despite differing antibody binding motifs. To put these findings into perspective, we studied prospectively relative frequency of viremia, kinetics of total and virus-specific IgG over time, and UL32 genetic variation in a cohort of therapy-naive patients (n=200). CMV-DNA was detected in 3% (6/200) of patients. The decay of total IgG was uniform (mean, 0.03; SD, 0.03) and correlated with that of IgG subclasses 1-4 in the paired samples available (n=64; p<0.001). Total CMV-specific IgG kinetics were more variable (mean, 0,02; SD, 0,06) and mean decay values differed significantly from those of total IgG (p=0.034). Boosts of CMV-specific antibody levels were observed in 49% (22/45) of CMV-seropositive patients. In contrast, VZV- and EBV-specific IgG levels decayed in parallel with total IgG levels (p=0.003 and p=0.001, respectively). VZV-specific IgG even became undetectable in 18% (9/50) of patients whereas CMV-specific ones remained detectable in all seropositive patients. The observed CMV-specific IgG kinetics were predicated upon the highly divergent kinetics of IgG specific for individual antigens - glycoprotein B-specific IgG were boosted in 51% and pUL32-specific IgG in 32% of patients. In conclusion, CLL patients have a preserved CMV-specific antibody response despite progressive decay of total IgG and IgG subclasses. CMV-specific IgG levels are frequently boosted in contrast to that of other herpesviruses indicative of a higher rate of CMV reactivation and antigen-presentation. In contrast to the reactivity of multiple different CLL-rAbs with pUL32, boosts of humoral immunity are triggered apparently by other CMV antigens than pUL32, like glycoprotein B.

Dataset Information

Prevalence and the impact of hypogammaglobulinemia in newly diagnosed chronic lymphocytic lymphoma patients.

Objective

Methods

Results

Conclusion

Publications

Prevalence and the impact of hypogammaglobulinemia in newly diagnosed chronic lymphocytic lymphoma patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets