Program DHC-Virtual
20 - 21 January 2021
Clinical Abstracts session 4
Abstract
HLA class I alloimmunization among hematological patients
21 January
12:06 12:18
R. Wijgers
Paper

Incidences and determinants of HLA class I alloimmunization among hematological patients

Renske Wijgers (1), Milou Bosch (1), Arnold van der Meer (2), Chantal Eijsink (3), Dorothea Evers (1)
(1) Radboud University Medical Center, Department of Hematology, Nijmegen, (2) Radboud University Medical Center, Department of Laboratory Medicine, Laboratory of Hematology, Nijmegen, (3) Radboud University Medical Center, Department of Laboratory Medicine, Laboratory for Diagnostics section Transfusion Medicine, Nijmegen
No potential conflicts of interest
Introduction

Intensive myelotoxic treatments in hematology require support of platelet transfusions. Refractoriness to donor platelets may be due to HLA class I alloimmunization and can severely complicate treatment support. Here, we assessed HLA class I alloimmunization incidences, subsequent refractoriness, and its main determinants in thrombocytopenic hematological patients undergoing disease-modifying treatments.

Methods

We performed an observational cohort study among all hematological patients who received disease-modifying treatments, including hematopoietic stem cell transplantation (HSCT), and were tested (at least once at a routine base) for the presence of HLA class I antibodies between January 1, 2015, to December 31, 2019, at the Radboudumc Nijmegen. Using Kaplan Meier analysis, we assessed cumulative HLA class I alloimmunization incidences according to (RBC and platelet) transfusion exposure and treatment phase. Furthermore, we quantified the association of various clinical conditions with the development of HLA class I alloantibodies via multivariate logistic regression analyses. Finally, the risk of platelet refractoriness was quantified according to HLA class I alloimmunization.

Results

HLA class I alloantibodies were detected in 45 of 603 (7.5%) treated hematological patients, of which 35 (77.8%) were parous females. Among HLA class I alloimmunized patients, 44.4% (20/45) were diagnosed with platelet refractoriness as compared to 3.2% (18/558) of non-alloimmunized patients.

Female risk was strongly associated to HLA class I alloimmunization (adjusted odds ratio (OR) 10.2, 95% confidence interval (CI) 4.4-23.3), mainly explained by a history of pregnancies and thus, likely, prior primary immunization. Only 1.9% (7/368) of males and 6.3% (3/48) of nulliparous females developed alloantibodies. In general, cumulative HLA class I alloimmunization incidences increased from 4.7% (CI 1.1-12.7) before any platelet unit received up to 25.6% (CI 8.8-45.9) after 40 platelet units received.

Furthermore, the incidence of HLA class I alloimmunization was significantly increased among patients with HLA class II antibodies (OR 15.5; CI 6.7-35.7). In addition, homozygosity in either HLA-A or HLA-B phenotype increased HLA class I alloimmunization risks, culminating to an OR of 6.04 (CI 1.27-28.65) in case of combined homozygosities.

Conclusion

The risk of HLA class I alloimmunization is dominantly determined by prior pregnancies. To a far lesser extent and despite current leukoreduction strategies, cellular blood transfusions also contribute, especially in case of multiply exposure. Consequently, HLA antibody screening at initiation of therapy may potentially merit optimal transfusion support of parous females, but can be safely postponed for males and nulliparous females.

Finally, the risk is increased in HLA class II alloimmunized and HLA class I homozygous individuals. Identification of such predictors may support phsysicians’ consciousness and thereby early identification of immune-mediated platelet refractoriness in hematological patients.

Register
×