Inclusion criteria and definitions
We retrospectively extracted from the monocentric lymphoma database of
Caen University Hospital all patients diagnosed with DLBCL between
January 2015 and December 2016, counted those with SEP performed at
diagnosis before receiving any specific treatments. Included patients
were categorized into two groups according to whether they exhibited
L-TGL or H-TGL on SEP at DLBCL diagnosis. Although CVID diagnosis
requires a threshold < 5 g/L of IgG isotype in addition to
other biological, clinical and anamnestic criteria(20–22), we chose
serum total gamma-globulin level because it is an easily available
biological test. We defined L-TGL as all TGL values ≤ 5.5 g/L on SEP as
it is < 50% of lower range of our laboratory norm similarly
to what was used in others studies in hematological malignancies(19) and
because IgG represent 75% of TGL in the absence of monoclonal
gammapathy, it would be unlikely to have more than 5g/L of IgG.
Exclusion criteria
As our hypothesis is based on L-TGL being a possible marker of PID or
SID related to the DLBCL condition, we excluded all patients exhibiting
an associated monoclonal peak on SEP; unrelated increased loss of serum
protein such as exudative enteropathy, extended burns or nephrotic
syndrome; previous treatment with cytotoxic drugs or immunosuppressant;
and previous PID or SID diagnosed before DLBCL.
Studied parameters
For all patients, demographic information at diagnosis, disease status,
chemotherapy regimen, Ann Arbor staging classification, central nervous
system involvement (CNS) involvement, and international prognosis index
(IPI) and outcome data were collected until the last follow-up date. For
biological data, C-reactive protein (CRP), albumin, lymphocytes count,
lactate deshydrogenase (LDH) and ferritin levels were collected at time
of diagnosis in the absence of an infectious process, and when
available, IgG, IgM, and IgA levels were implemented. We considered the
albuminemia/gammaglobulinemia ratio (AG ratio) to discriminate possible
causes for L-TGL : 1) For an unspecific decrease in TGL related to
general state impairment, a decrease in albumin should be associated to
decrease in TGL, with an unaltered AG ratio; 2) For a specific decrease
in TGL directly related to our hypotheses, i.e., L-TGL due to either an
undiagnosed PID or a SID developed with DLBCL, the albumin level should
be close to normal value, resulting in an increase in the AG ratio.
Statistical analyses
Data were compiled as the median [range] or a number (%).
Continuous variables were analyzed using the Mann-Whitney test, and
Fisher’s test was used to compare categorical variables. A p value
< 0.05 was considered statistically significant.
Predictors of death in DLBCL were evaluated using COX proportional
hazard models. All the variables showing a univariate p-value less than
0.20 were entered into a multivariable logistic regression model.
Results were expressed as hazard ratios (HRs) with 95% confidence
intervals (95% CI). Two-sided P-values lower than 0.05 were considered
significant.
Overall survival in DLBCL and subgroups L-TGL and H-TGL were analyzed
using the Kaplan-Meier method, and these variables were compared using
the log-rank test.
All statistical analyses were performed using GraphPad Prism software
(7.0) and JMP 9.0.1 (SAS Institute Inc., Cary, NC, USA).