Results
Out of 122 patients diagnosed with DLBCL during the pre-specified
period, 96 (74.8%) had a SEP before any chemotherapy, and among them,
12 (12.5%; 8 males; median age: 68 [55-89] years) had L-TGL.
Demographical and biological data for both the L-TGL (n=12; TGL≤5.5 g/L)
and H-TGL (n=84; TGL>5.5 g/L) subgroups are summarized in
Table 1.
Ann Arbor staging and International prognosis index were comparable
between L-TGL and H-TGL groups. However no Richter syndrome was reported
in the L-TGL group, but 2 were described in the H-TGL group.
IgG level was lower in L-TGL regardless of albumin and
inflammatory status
Immunoglobulin isotype levels were available only in two-thirds (8/12)
of L-TGL and in approximately half (46/84; 55%) of H-TGL patients,
respectively: the median levels of IgG were significantly lower
(p<0.001) in the L-TGL subgroup than in the H-TGL subgroup and
in parallel with TGL levels, whereas the IgA and IgM levels were not
significantly different (p=0.31 and 0.32, respectively). No patient had
detectable viral load for Epstein Barr virus or Cytomegalovirus or
active bacterial infection at diagnosis.
The serum total protein level was lower (p<0.01) and AG ratio
was higher (p<0.01) in L-TGL than in H-TGL patients. Even
though higher serum ferritin levels were found in L-TGL patients than in
H-TGL patients (p=0.02), which could indicate higher biological
inflammatory status or specific organ involvement, the levels of CRP
were comparable in both subgroups.
Lymphocyte level was significantly lower in L-TGL patients (p=0.02), but
was comparable between L-TGL and H-TGL deceased patients (Table 1).
Death rate and infection related death are higher in L-TGL
subgroup
The mortality rate was higher in L-TGL (mortality rate: 10/12 [83%]
versus 22/84 [26.2%]; p=0.03) and median follow-up duration was
shorter (follow-up duration: 15.2 months versus 55.53 months;
p<0.001) than in H-TGL subgroup (Table 1). Similarly, the rate
of death caused by an infection was significantly higher in L-TGL than
in H-TGL patients (10/10 [100%] versus 6/22 [27.3%];
p<0.001), as shown in Table 1. In H-TGL patients, deaths were
caused by DLBCL progression for most patients (54.5%; 12/22 deceased
patients), whereas the remaining patients (18.2%; 4/22 deceased
patients) died from other causes that were independent of the background
disease or related treatments.
Regarding infection-related deaths, no opportunistic infection was
identified. All 10 deaths in L-TGL subgroup and 3 out of 6
infection-related deaths in H-TGL subgroups were related to
pleuro-pneumopathy, either associated or not with ear, nose and throat
infections and/or Streptococcus pneumoniae . The remaining 3 H-TGL
infection-related deaths were caused by septic shock-complicated
pyelonephritis, staphylococcus bacteremia and cutaneous cellulitis of
the diabetic foot.
As seen on Kaplan Meier curves shown in Figure 1 , the survival
of L-TGL patients was significantly lower (p<0.001) than all
the other groups considered in the whole DLBCL patients cohorts,
including H-TGL patients (n=84), all patients who had a SEP (i.e. L-TGL
and H-TGL patients considered together; n=96) and patients who didn’t
get a SEP at diagnosis (n= 26).
No concordance between TGL and albumin levels in L-TGL and
H-TGL subgroups
In addition to the comparisons of demographics, clinical and biological
characteristics in both L-TGL and H-TGL subgroups, shown in Table 1;
both subgroups were similar for all clinical and usual biological
parameters including albumin level, except for the lower median TGL
(p<0.01) and IgG levels (p<0.01) in L-TGL patients
than in H-TGL patients, as expected. Moreover the AG ratio was higher in
L-TGL than in H-TGL patients (p<0.01) indicating that TGL
decrease was more pronounced than that of albumin, suggesting that
albumin serum level was unrelated to TGL in our DLBCL patients
subgroups.
Chemotherapy regimen was comparable between L-TGL and H-TGL
subgroups
The distribution of chemotherapy regimens is shown in Table 2 between
deceased and living patients in both the L-TGL and H-TGL subgroups.
First-line chemotherapy was the R-CHOP regimen (21-day interval;
rituximab, cyclophosphamide, hydroxyadriamycin, vincristine, and oral
prednisone) for 85 (88.5%) patients in total, whereas 3 others, all in
the H-TGL subgroup, received ACBVP (two-week interval; adriamycin,
cyclophosphamide, bleomycin, vindesine, and oral prednisone) followed by
sequential consolidation therapy consisting of two cycles of
methotrexate because of their younger age; 7 others (2 and 5 in the
L-TGL and H-TGL subgroups, respectively) received the RMPV regimen
(rituximab, methotrexate, procarbazine, and vincristine) because of
cerebral involvement, and finally, the remaining patient was an elderly
patient in the H-TGL subgroup who refused any chemotherapy.
A second-line chemotherapy regimen was chosen for 37 of the 96 patients,
including 9 and 28 patients in the L-TGL and H-TGL subgroups
respectively, whereas third- and fourth-line chemotherapy regimens were
proposed for 10 patients and 2 patients, respectively. As shown in Table
2, the characteristics of patients who had died and those who remained
alive at last follow-up in each subgroup appeared comparable, except for
lymphoma stage: stage I lymphomas were significantly overrepresented in
H-TGL patients who remained alive (p=0.02; Table 2). Of note, stage IV
lymphoma and central nervous system involvement were not significantly
associated with death among H-TGL patients, although the low number of
events precluded any firm conclusion (Table 2).
Hypogammaglobulinemia at diagnosis is associated with higher
risk of
death
Table 3 represents hazard ratio for the different variables studied
using a cox proportional hazards model. Ann Arbor stage IV was
positively associated with the occurrence of death (HR 3.47 (1.61-7.47),
p < 0.01). More interestingly, L-TGL was also found to be
independently associated with a higher risk of death (HR 12.8
[4.93-34.31], p <0.001) while H-TGL was associated with a
lower risk of death (HR 0.21 [0.09-0.46], p <0.01).