Page 176 - 2021_04-Haematologica-web

V. Brixner et al.
Table 4. Efficacy endpoints (based on per-protocol anlysis). Parameter
UVC
75
249 245
13.18 ± 5.98
11.80 - 14.56 3.03 (1.03-5.04) 18.70 (6.33-31.07)
22.94 ± 11.23 20.36 - 25.53 15.76 ± 9.82 13.50 - 18.02 9.18 ± 5.65 7.88 - 10.47 3.32 ± 2.22 3.27 ± 2.10 10.82 ± 7.13 2.70 ± 1.80 2.47 ± 2.19
Control
71
183 181
16.21 ± 6.18 14.73 - 17.70
28.36 ± 12.65 25.33 - 31.40 20.37 ± 11.96 17.50- 23.24 11.62 ± 6.24 10.12 - 13.12 2.58 ± 1.85 2.55 ± 1.79 8.54 ± 6.04 3.06 ± 2.14 2.10 ± 2.25
P
0.030 0.028
Patients
Platelet transfusions
Platelet transfusion episodes* Primary endpoint†
1-hour CCI
Secondary endpoints† 1 hour-CI
24-hour CI 24-hour CCI
Platelet transfusions per patient
Platelet transfusion episodes per patient* Total dose of platelets transfused per patient‡ Interval between platelet transfusions
Red cell transfusions per patient
n
n n
mean ± SD
CI 95%
mean difference (CI 95%) mean difference (%) (CI 95%)
mean ± SD
CI 95% mean ± SD
CI 95% mean ± SD
CI 95%
n, mean ± SD n, mean ± SD
x 1011, mean ± SD Days, mean ± SD
n, mean ± SD
0.030
0.028
0.040
0.372
0.312
*A transfusion episode was defined as two or more platelet transfusions on the same day where the interval between two consecutive transfusions was less than 2 hours.†Mean corrected count increment (CCI) and count increment (CI) values were calculated as the mean of the average CCI/CI of all transfusions per patient. ‡Only per-protocol trans- fusions were included in this analysis. UVC: ultraviolet C; SD: standard deviation; CI: Confidence Interval.
Table 5. Refractoriness to platelet transfusions (based on intention-to-treat analysis).
Parameter
Refractory episodes*
Patients with at least one refractory episode Single episode of refractoriness
Multiple episodes of refractoriness Immunological refractoriness†
Antibodies to HLA class I
Antibodies to HPA
Antibodies to UVC-related neoantigens
n
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
UVC
15
14 (16.09)
13 (92.86)
1 (7.14)
2 (14.29)
2 (100.00)
0 (0.00)
0 (0.00)
Control
6
6 (7.14)
6 (100.00)
0 (0.00)
1 (16.67)
1 (100.00)
0 (0.00)
0 (0.00)
P
0.055
0.095
1.000
*Episode of “clinical” refractoriness, defined as two consecutive transfusions, each with a 1-hour CCI < 7.5. †Episode of “clinical” refractoriness in the presence of platelet anti- bodies. No immunologic refractoriness due to seroconversion was recorded. UVC: ultrviolet C; HLA: human leukocyte antigen; HLP: human platelet antigen.
gests that the hemostatic function of UVC-treated and ref- erence platelets was equivalent.
An increase in the utilization of platelet units due to reduced increments of pathogen-reduced platelets would have clinically and economically relevant effects. While randomized controlled clinical trials consistently report that pathogen-reduced platelets are associated with a higher number of transfusions per patient, surveillance studies did not show increased usage of PC after universal adaption of a routinely used PR technology.36,37 This con- tradictory result may be explained by the fact that PR implementation in routine practice is often associated with changes in PC specifications and platelet supply logistics that can impact platelet quality. In routine prac- tice, the requirement for generally higher platelet contents in pathogen-reduced PC compared to untreated PC may be a feasible strategy to compensate for the lower recov- ery of pathogen-reduced platelets, although this could require more blood donations in several settings.38
Adverse events overall occurred at similar frequencies and severities in the treatment and control groups. In par- ticular, transfusion-related adverse events were infrequent and mainly low-grade, in line with current hemovigilance data.39,40 The higher number of such low-grade transfu- sion-related adverse events in the UVC arm is due to the fact that episodes of platelet refractoriness, which were more frequently observed in patients receiving UVC-treat- ed platelets, were recorded as transfusion-related low grade 1 and 2 adverse events at some study sites. No unusual adverse events were associated with the transfu- sion of UVC-treated platelets. Rates of platelet antibodies were low and similar in both arms. Most of the patients with platelet antibodies were pre-immunized prior to the first study platelet transfusion. Similar to the findings reported for other DNA-targeted PR systems, UVC treat- ment was previously shown to impair direct antigen pres- entation of antigen-presenting cells in PC, which may pos- sibly reduce alloimmunization in transfusion recipients.13
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