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4040 Impact of Non-Immune Factors on Platelet Transfusion Responses in an Allo-Immunized Cohort

Program: Oral and Poster Abstracts
Session: 401. Blood Transfusion: Poster III
Hematology Disease Topics & Pathways:
Research, Clinical Research, real-world evidence
Monday, December 11, 2023, 6:00 PM-8:00 PM

Josefine Bribiesca Rodriguez1*, Aaron Boothby, MD2, Matthew Tanner, MD1*, Hossein Rajali3*, Lauge Sokol-Hessner, MD4*, Rida Hasan, MD5, Danny Youngs, BS, CHS(ACHI)6*, Idoia Gimferrer, MD/PhD, D(ACHI)6*, Sandhya R Panch, MD7 and Hamilton Tsang, MD8*

1University of Washington, Seattle, WA
2Hematology-Oncology Fellowship Program, University of Washington, Saint Paul, MN
3Poznan University of Medical Sciences, Poznan, Poland
4Division of General Internal Medicine, University of Washington, Seattle, WA
5Transfusion Medicine Division, University of Washington, Seattle, WA
6Blood Works NW, Seattle, WA
7Hematology /Transfusion, Fred Hutchinson Cancer Center, Seattle, WA
8Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA

Background: Patients with hematologic malignancies and/or hematopoietic stem cell transplantation (HSCT) recipients often require platelet transfusion support for extended periods. This can result in platelet transfusion refractoriness (PTR) from HLA alloimmunization in up to 30% of individuals. These medically complex patients may also have splenomegaly, fevers and other factors which contribute to PTR. Consequently, they may demonstrate variability in immediate platelet recovery (at 0-2 hours post-transfusion), and in subsequent platelet consumption (at 18-24 hours) despite receiving HLA-selected platelet products. We sought to examine patient and product related factors which impacted platelet transfusion response in a cohort of HLA-alloimmunized platelet transfusion refractory patients.

Methods: From April 2021 to June 2023, HLA-alloimmunized (PRA >50%) subjects who required three or more HLA selected platelet units were identified at the Fred Hutchinson Cancer Center/University of Washington. Data were obtained on patient demographics, diagnoses, Panel Reactive Antibodies (PRA %) and factors shown to be associated with poor platelet responses (spleen size, disseminated intravascular coagulation (DIC), bleeding, selected medications, history of hematopoietic stem cell transplant (HSCT) and/or graft versus host disease (GVHD), ABO compatibility, and product age). Platelet corrected count increments (CCI) were calculated for each transfusion. Non-HLA factors potentially contributing to CCIs at 0-2 and 18-24 hours post-transfusion were compared among HLA-compatible (either 4/4 HLA matched without HLA antigen mismatches, or with permissive mismatches (defined as cumulative a mean fluorescent intensity (MFI) <10,000 on the Luminex donor specific HLA antibody testing platform)) and HLA incompatible transfusions (cumulative MFI >10,000 or random donor apheresis products).

Results: Of the 420 patients screened, 75 had sufficient records for inclusion. These subjects received 2729 platelet transfusions, an average of 36 transfusions per patient over 5.2 (± 4.1) months. Post transfusion platelet counts were available for 1528 transfusions. All platelet products were leukoreduced, irradiated, single donor apheresis products. Patients were predominantly Caucasian (70.7%; n=53/75), female (82.7%; n=62/75), aged 57 (±14.9) years. The primary diagnosis was Acute myelogenous leukemia or myeloproliferative disorder in most cases (88%; n=66/75). 58.7% (n=44/75) of patients were HSCT recipients (3 auto-; 41 allo-HSCT). Average PRA among patients was 72.4%±22.2%. 25 patients had splenomegaly. Among HLA-compatible transfusions, average CCIs at 0-2 and 18-24 hours were 17,088 and 6,666. In HLA-mismatched/random donor transfusions, average CCIs at 0-2 and 18-24 hours were 11,489 and 2,786; HLA compatible products increased CCIs by 5,599 and 3880 at 0-2 and 18-24 hours. In both groups splenomegaly had the most consistent association with poor CCI at both time intervals (Figures A and B).

Conclusions: In this cohort of individuals with HLA-alloimmunization mediated PTR, the administration of HLA-compatible products offset the impact of other detrimental factors generating adequate CCIs at 0-2 and 18-24 hours. Among patients with splenomegaly, CCIs were lower despite HLA compatible product administration. In the same individuals, HLA-incompatible/random donor products negatively impacted CCIs overall and the negative effect of other concomitant non-immune/product-related factors was additive. Our data highlights the need to account for non-HLA related conditions while evaluating CCI response following each HLA-selected product transfusion, and to further explore any interactions among such factors. Next steps include conducting a multivariate analysis and developing a predictive model for platelet transfusion response in HLA-alloimmunized recipients who have concomitant non-immune or product related risk factors.

Disclosures: Panch: Sanofi: Consultancy, Other: Advisory Board; Sobi: Consultancy, Speakers Bureau. Tsang: Roche: Current equity holder in publicly-traded company; Pfizer: Current equity holder in publicly-traded company; Johnson & Johnson: Current equity holder in publicly-traded company.

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