Study population
Between October 20, 2016, and November 20, 2021, 118 people were diagnosed with AL or MDS and had platelet counts >20×109/L. The clinical baseline characteristics of patients with kin-donated platelet transfusion (treatment group) and unrelated donor platelet-transfusion (comparator group) were generally similar (Table 1). After excluding ineligible patients, 66 patients were included in the study: 31 in the treatment group and 35 in the comparator group. The cohort construction flowchart is shown in Figure 1.
Table 1 Patient characteristics
|
Treatment group (n=31)
|
Comparator group (n=35)
|
Male/female, n
|
16/15
|
19/16
|
Age, mean ± SD, y
|
47±16
|
51±19
|
Body surface area, mean ± SD, m2
|
1.71 ± 0.52
|
1.69 ± 0.49
|
Diagnosis, n (%)
|
|
|
Acute myelogenous leukemia
|
13(41.9)
|
16(45.7)
|
Acute lymphoblastic leukemia
|
16(51.6)
|
12(34.3)
|
Myelodysplastic syndromes
|
2(6.5)†
|
7(20.0)
|
Laboratory values at randomization, mean ± SD
|
|
|
Platelet count, 109/L
|
13±7
|
12±8
|
Hemoglobin, g/L
|
89±22
|
84±19
|
White cell count, 109/L
|
1.9±0.4
|
1.8±0.6
|
Activated partial thromboplastin time, s
|
31.5±8.9
|
33.3±9.2
|
Prothrombin time, s
|
15.1±3.1
|
14.9±3.2
|
Fibrinogen, g/L
|
3.5±1.9
|
3.4±2.5
|
Medication and medical history, n (%)
|
|
|
Anticoagulant/antiplatelet therapy
|
0(0)
|
0(0)
|
Bleeding
|
2(9.5)
|
3(8.6)
|
Prior platelet transfusion
|
29(93.5)
|
33(94.3)
|
Prior red cell transfusion
|
31(100)
|
35(100)
|
Prior pregnancy
|
14(45.2)
|
17(48.6)
|
Blood type, n (%)
|
|
|
A
|
5(16.1)
|
7(20.0)
|
B
|
15(48.4)
|
16(45.7)
|
AB
|
3(9.7)
|
5(14.3)
|
O
|
8(25.8)
|
7(20.0)
|
Rh+
|
31(100)
|
35(100)
|
†P <0.05.
Bleeding assessment
Data on bleeding events during the evaluation period are presented in Table 2. WHO grade 1, 2, 3, or 4 bleeding events occurred in 38.7% of patients in arm treatment (12 of 31 patients) compared with 82.9% of patients in arm comparator (29 of 35 patients). The comparison between the two groups showed a significant superiority of group treatment (P=0.001). Therefore, this study did not show that group treatment was superior to group comparator in terms of the frequency of WHO grade 1, 2, 3 or 4 bleeding events.
The number of days with WHO grade 1, 2, 3, or 4 bleeding events during the evaluation period was lower in arm treatment than in arm B (median 2 days lower). The time to first bleeding episode was significantly longer in group treatment than in group comparator (median 3 days longer). The proportion of patients with WHO grade 2, 3, and 4 bleeding in group treatment was not significantly different from that in group comparator.
Table 2 Bleeding complications*
|
Treatment group (n=31)
|
Comparator group (n=35)
|
Primary end point
|
|
|
WHO grade 1,2, 3 or 4 bleeding, n (%) ‡
|
12(38.7)
|
29(82.9)
|
No. of days form first episode of grade1,2,3,or 4 bleeding, median (IQR) †
|
4(2-6)
|
2(1-7)
|
No. of days with grade 1,2,3,or 4 bleeding, median (IQR)
|
2(1-6)
|
5(2-7)
|
WHO grade 3 or 4 bleeding, n (%) †
|
1 (3.2)
|
1 (2.9)
|
Highest grade of bleeding, n (%)
|
|
|
None or grade 1
|
25(80.6)
|
27(77.1)
|
Grade 2
|
5(16.1)
|
7(20.0)
|
Grade 3
|
1(3.2)
|
1(2.9)
|
Grade 4
|
0(0)
|
0(0)
|
Type of cancer
|
|
|
Acute myelogenous leukemia ‡
|
4 (30.8)
|
13 (81.2)
|
Acute lymphoblastic leukemia ‡
|
6 (37.5)
|
11 (91.7)
|
Myelodysplastic syndromes †
|
2 (100)
|
5 (71.4)
|
* Plus-minus values are means ±SD. In the World Health Organization (WHO) grading system, bleeding episodes are classified as grade 1 (mucous membrane hemorrhage), grade 2 (moderate; red-cell transfusion not needed immediately), grade 3 (severe; requiring red-cell transfusion within 24 hours), or grade 4 (debilitating or life-threatening)12. (12 ) †P <0.05. ‡ P <0.001.
Platelet Transfusions
Most platelet transfusions were prophylactic, with no significant differences in platelet counts in the body before platelet transfusion between the two groups and comparable platelet content in transfused products. This study mainly observed the increase in platelet count and CCI at 24 hours (range, 14-24 hours) and 72 hours (range, 52-72 hours) after platelet transfusion in the two groups. The specific results are shown in Table 3. The platelet increase in group treatment at 24 hours The amount was significantly higher than that in group comparator (95% confidence interval [CI], 25.9 to 34.9; P=0.001) (Fig. 2A). The CCI value of group treatment was also significantly higher than that of group comparator at 24 hours (95% confidence interval [CI], 4.0 to 8.2; P=0.001) (Fig. 2B). At 72 hours, the increased number of platelets and CCI in group treatment were higher than those in group comparator, but there was no significant difference. In addition, group treatment basically did not have PTR, but the proportions of 24-hour CCI <10 and PPR <20% in group comparator were 68.5% and 54%, indicating that Related donor Platelet transfusion can reduce the occurrence of PTR.
Table 3 Platelet transfusion increment
|
Treatment group (n=31)
|
Comparator group (n=35)
|
P
|
Efficacy parameters, mean ± SD
|
|
|
|
Count increment 24 h, 109/L
|
44.6±10.5
|
10.5±6.9
|
<0.001
|
CCI 24 h
|
29.8±7.0
|
7.0±4.6
|
<0.001
|
Count increment 72 h, 109/L
|
14.1±4.1
|
7.9±4.4
|
<0.01
|
CCI 72 h
|
9.4±2.7
|
5.3±2.9
|
<0.05
|
Transfusion failure rate, n (%)
|
|
|
|
CCI 24 h, ≤0
|
0(0%)
|
4(11.4%)
|
|
CCI 24 h, <4.5
|
0(0%)
|
7(20.0%)
|
|
CCI 24 h, <10
|
0(0%)
|
13(37.1%)
|
|
PPR 24 h, ≤20%
|
1(3.2%)
|
19(54.0%)
|
<0.001
|
Safety
Common platelet transfusion complications such as fever, anaphylaxis, and hemolysis did not differ between the two groups (Figure 3). There was no event of transfusion associated graft versus host disease (TA-GVHD) in the treatment group and in the comparator group, and there was 1 case of serious adverse event (SAE) in the treatment group, which was judged by the clinician to be heart failure caused by massive rehydration during platelet transfusion. The percentages of confirmed transfusion adverse event were 19.4% and 25.7% in the treatment and comparator groups. The majority of the transfusion adverse event in both groups resulted in no or only minor morbidity.
Subgroup Analysis
In the treatment group of 31 patients, we analyzed the transfusion effect of platelet donors and recipients with different HLA antigen matching. We found that compared with HLA-A, -B, and -C, the infusion of HLA-A, -B, and -C at all three sites was more effective (Fig. 4A). However, the different blood types of platelet donors and recipients did not affect the transfusion effect (Fig. 4B).