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Efficacy of UVC-treated platelets
Table 2. Platelet transfusion characteristics and pre-transfusion count (based on intention-to-treat anlysis).
Parameter
Platelet transfusions Apheresis platelets Buffy-coat platelets
Transfusion episodes*
Single dose
Multi-dose
Indication for platelet transfusion†
Trigger based
Prior to intervention Treatment of active bleeding
ABO incompatibility† Major
Minor
Major and minor No mismatch
Platelet dose per single transfusion†
Storage time†
Mean pre-transfusion platelet count*
n
n
n
n
n (%) n (%)
n (%) n (%) n (%)
n (%) n (%) n (%) n (%)
x 1011, mean
Days, mean
± SD ± SD
UVC
320 223
97
316 312 (98.73) 4 (1.27)
302 (98.69) 3 (0.98) 1 (0.33)
32 (10.46)
82 (26.80)
10 (3.27)
182 (59.48)
3.26 ± 0.37
2.87 ± 1.18
12.58 ± 6.64
Control
248 166
82
245 242 (98.78) 3 (1.22)
236 (100.00) 0 (0.00)
0 (0.00)
22 (9.32)
52 (22.03)
13 (5.51)
149 (63.14)
3.30 ± 0.37
2.93 ± 1.23
12.14 ± 7.70
P
0.041
0.060
0.396
0.038
0.211
0.353
0.242
0.488
0.544
109/L, mean ± SD
*Transfusion episode = two or more platelet transfusions on the same day, whereby the interval between two consecutive transfusion is less than 2 hours †Only per-protocol transfusions were included in these analyses. UVC: ultraviolet C; SD: standard deviation.
UVC groups was 18.24% (95% Cl: 6.40-30.08). For analy- sis in the PP population, 75 patients in the UVC arm and 71 patients in the control arm were evaluable. The mean 1-hour CCI value was 13.18% (95% CI: 11.80-14.56) in the UVC group and 16.21% (95% CI: 14.73-17.70) in the control group. The mean difference in 1-hour CCI between the control and UVC groups was 18.70% (95% CI: 6.33-31.07). Thus, the upper bounds of the 95% CI slightly exceeded the specified margin of 30% with both ITT and PP approaches, indicating that non-inferiority cannot be claimed (Tables 3 -4, Figure 2). Results for all secondary efficacy endpoints are given in Tables 3-4. For the ITT population, the mean values for platelet count increment parameters were lower in the UVC group than in the control group: 18.5% for 1-hour CI, 20.4% for 24- hour CI and 19.2% for 24-hour CCI. Patients in the UVC arm received about 25% more platelet transfusions than patients in the control arm. Accordingly, the mean total dose of platelets transfused per patient was significantly higher in the UVC arm than in the control arm. The mean time interval between platelet transfusions and the mean number of RBC transfusions did not differ significantly between arms. Comparable results were obtained for the PP analysis.
Alloimmunization and refractoriness
Antibodies against platelet antigens were detected in 10.3% and 8.3% of patients of the UVC arm and control arm, respectively, prior to the first study platelet transfu- sion. Platelet antibodies developed in six patients who tested negative at the beginning of the study: one patient in the UVC arm (human leukocyte antigen [HLA] class I) and five patients in the control arm were affected (three HLA class I, one human platelet antigen [HPA], one HLA class I plus HPA; data not shown). The number of refractory episodes and the number of patients with refractory episodes did not differ significantly between groups (Table 5). Immunological refractoriness due to HLA class I anti-
bodies was determined in two patients in the UVC arm and one patient in the control arm; the HLA antibodies were detectable prior to the first study platelet transfusion in all three cases. Platelet antibodies to UVC-related neoantigens were not detected in this study.
Safety
A total of 1,374 adverse events were documented, 741 in the UVC arm and 633 in the control arm (Table 6). At least one adverse event occurred in 85 patients in the UVC group and in 80 patients in the control arm (Online Supplementary Table S2). The majority of adverse events were non-serious grade 1 and 2 events that were unrelated to the platelet transfusions. The number of mild grade 1 and 2 non-serious adverse events related to platelet trans- fusion was significantly higher in the UVC arm than in the control arm. The difference between arms was still of only borderline significance when we compared the ratios per platelet transfusion and patient that were calculated to account for the higher number of platelet transfusions in the UVC arm. The symptoms of the reported transfusion- related adverse events were mainly those known to be associated with platelet transfusions, such as chills, pyrex- ia, hypersensitivity (allergic reactions), refractoriness and rash (Online Supplementary Table S3). Ten serious adverse events were recorded in each treatment arm; they affected ten patients in the UVC arm and eight in the control arm; none of these serious adverse events were related to the platelet transfusions. Severe bleeding (WHO grade 3 and 4) was observed in one patient in the control arm but in none in the UVC arm. There was no statistically signifi- cant difference in mortality between arms (Table 6).
Discussion
This multicenter, randomized controlled study was designed to evaluate the efficacy and safety of pathogen-
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