Page 166 - Haematologica Vol. 107 - September 2022

ARTICLE - Immune deficiency during RM after transplantation L. Bouard et al.
bolic and bone marrow responses, as well as the use of salvage therapy, were also taken into account to analyze patients’ response to induction. Delay between ASCT and first rituximab injection was selected to report post-ASCT hematopoietic restoration. We also analyzed the impact of the number of CD34 stem cells injected. We analyzed the number of rituximab injections in order to determine its dose effect involvement in infectious risk.
For univariate analysis, variables were compared with a Fischer test. Multivariate analysis is based on logistic re- gression, and includes data from the univariate analysis with a P-value <0.20.
Results
Patient characteristics, occurrence of clinical events and infections sites
The Obs and RM arms included 120 patients each. Patient characteristics and distribution are reported in the On- line Supplementary Appendix. No significant difference was observed between the two arms as previously pub- lished. Concerning febrile events, the difference between the two arms was only statistically significant after 1 year post ASCT (periods 3 and 4, Table 1), with 1 of 107 pa- tients (0,9%) in the Obs arm versus seven of 99 patients (7,1%) in the RM arm; and two of 89 patients (2,3%) in the Obs arm versus ten of 97 patients (10,3%) in the RM arm, P=0.03 and P=0.02; respectively. Median duration of fever episode was not different between the two arms: 1 day (range, 1-3) in the Obs arm versus 2 days (range, 1-15) in the RM arm, P=0.20. Concerning infectious events, there were significantly more infections reported in the RM
arm during period 3: 28 of 99 patients (28.3%) experi- enced an infection versus 11 of 107 patients (10.3%) in the Obs arm, P=0.001 (Table 1). More than 50% of infectious episodes were located in the upper or lower respiratory tracts, regardless of the arm treatment or period. In the RM arm, infections sites revealing a significantly in- creased incidence were: upper and lower respiratory tracts; respectively P=0.0025 and P=0.008, digestive in- fections; P=0.0003 and bacteriemia; P=0.04; Figure 1. It should be noted that there were four and five acute pneumonia in the Obs and RM arms, respectively. In the RM arm, 13 episodes of bacterial diarrheas were re- ported: six Clostridium dificile colitis, five Campylobacter jejuni documentations, one Salmonella enterica docu- mentation and one Escherichia coli documentation. The digestive tract was the only infection site with a larger proportion of total infectious episodes in the RM arm, compared to the Obs arm, 14.2% versus 3.8% respect- ively, P=0.05. Other infection sites showing similar inci- dences and proportions in both arms, are reported in Figure 1. Of note, there was no infections due to Pneu- mocystis jiroveci or LEMP due to JC virus in any arm.
In total 55 hospitalizations due to infections were re- ported, involving 45 of 239 patients (18.8%, Table 1). There were no differences between the two arms in any period, P=0.61, P=1.0, P=0.09 and P=0.10 for periods 1, 2, 3 and 4, respectively. Median hospitalization duration was not different: 6 days (range, 1-25) in the Obs arm versus 6 days (range, 1-27) in RM arm, P=0.78.
There was no death related to infectious complications.
Immune restoration and biologic parameters
The data available for each parameter is reported in the Online Supplementary Table S2.
Table 1. Number of patients concerned by febrile events, infectious events hospitalizations due to infections and γ globulin substitution in the two arms according to post autograft.
< 6 months
6-12 months
12-24 months
24-36 months
Obs N=120
RM N=119
P
Obs N=116
RM N=104
P
Obs N=107
RM N=99
P
Obs N=89
RM N=97
P
Fever episodes N patients (%) N events
7 (5,8) 7
10 (8,4) 11
0,440
1 (0,9) 1
5 (4,8) 5
0,103
1 (0,9) 1
7 (7,1) 8
0,030
2 (2,2) 3
10 (10,3) 14
0,025
Infectious episodes N patients (%)
N events
11 (9,2) 12
16 (13,4) 19
0,296
9 (7,8) 11
16 (15,4) 22
0,075
11 (10,3) 15
28 (28,3) 45
0,001
13 (14,6) 13
22 (22,7) 41
0,159
Hospitalizations N patients (%) N events
8 (6,7) 8
10 (8,4) 11
0,611
5 (4,3) 5
4 (3,8) 5
1,000
3 (2,8) 3
8 (8,1) 9
0,092
3 (3,4) 4
9 (9,3) 10
0,101
γ globulin substitution
N patients (%) N events
2 (2) 9
6 (6,2) 19
0,171
2 (2) 10
5 (5,2) 41
0,259
5 (5) 23
11 (11,3) 48
0,0075
1 (1) 3
19 (19,6) 165
<.0001
Obs: observation arm; RM: rituximab maintenance arm.
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