Memorial Sloan Kettering Cancer Center New York, New York, United States
Background/Case Studies: Platelet refractoriness is generally defined as corrected count increment (CCI) < 7,500/µL to platelet transfusion on two separate occasions . It is a challenging clinical problem in thrombocytopenic patients due to risk of spontaneous life-threatening bleeding, increased hospital stays and decreased survival. The etiology of refractoriness can be due to immune (alloimmunization to HLA or platelet antigens) or non-immune factors such as splenomegaly, medication, and sepsis. HLA alloimmunization is assessed by solid phase testing using beads coated with individual HLA antigens and HLA antibody avidity expressed as mean fluorescent intensity (MFI). Level of alloimmunization is estimated by calculated panel antibody reactivity (cPRA). Alloimmunization is a dynamic process, and degree of alloimmunization may change over time. However, data on the utility of repeat HLA testing in platelet refractory patients is lacking. The objective of this study was to assess if degree of HLA alloimmunization changes over time.
Study
Design/Methods: Patient medical records were retrospectively reviewed for demographics, transfusion records and HLA class I antibody testing from 1/2020 to 8/2022 at a large cancer center. HLA antibody testing was performed at a reference lab using Luminex-single antigen bead assays. Antibodies with MFI > 4000 were considered clinically significant, and MFI 1500-4000 were considered grey zone antibodies. Number of clinically significant HLA antibodies, grey zone antibodies and cPRA were compared at initial and repeat testing. Data were analyzed using GraphPad Prism software (GraphPad, San Diego, CA). Groups were compared using unpaired t-test and criterion for significance was P-value < 0.05.
Results/Findings: Overall, 96 patients [50 M, median age 62 years (15-93); 46 F, median age 66 (5-82)] had HLA class I antibody testing performed. 33/46 (71.6%) F and 3/50 (6%) M were positive for HLA class I antibodies. Repeat HLA antibody testing was performed in 14 patients with a mean time interval of 137.4 days (34-541) between testing . Between initial and repeat testing, a mean of 31.4 platelet units (5-157) was transfused per patient. There was no significant difference in clinically significant antibody numbers (43.5 ± 4.63 vs. 43.14 ± 4.32; mean ± SEM; initial vs. repeat testing; p 0.9), grey zone antibody numbers (5.07 ± 1.03 vs. 6.64 ± 1.08; mean ± SEM; initial vs. repeat testing; p=0.3), clinically significant antibody cPRA (92.5 ± 5.39 vs. 92.5 ±5.44; mean ± SEM; initial vs. repeat testing; p=1.0), or grey zone antibody cPRA (20.5 ± 4.74 vs 35.07 ±7.67; mean ± SEM; initial vs repeat testing; p=0.11). Conclusions: These data suggest that degree of HLA alloimmunization does not change significantly over time in platelet refractory patients. Repeat alloimmunization testing may have limited clinical value.
Importance of research: Immune related platelet refractoriness is a challenging clinical problem in thrombocytopenic patients affecting outcome. Management includes class I HLA antibody assessment and transfusion support with matched platelets. Alloimmunization is a dynamic process, and degree of alloimmunization may change over time. However, data on the utility of repeat HLA antibody testing in immune related platelet refractory patients is lacking. Our study investigated this crucial clinically relevant question.
