Background: Patients with hematologic malignancies require prophylactic or curative platelet transfusions to prevent or treat bleeding. Treatments such as chemotherapy, radiotherapy, and hematopoietic stem cell transplantation cause persistent thrombocytopenia, necessitating platelet transfusions. However, class I HLA antibodies can cause a serious complication: immune-mediated platelet refractoriness. The mechanisms of alloimmunization are incompletely understood. We explored the immunogenicity of HLA molecules and the phenotype of the HLA-specific CD4 + T cells involved in alloimmunization. Study Design and Methods: We investigated the role of HLA molecules in platelet transfusion immunogenicity in a retrospective cohort study on men with specific anti-HLA who had undergone transfusion. We investigated the presence and phenotypic profile of HLA-specific CD4 + T cells in alloimmunized patients included in long-term platelet transfusion programs for hematologic malignancies. Results: More than 50% of the transfused subjects displayed an antibody response against HLA-B57 or-B58. HLA-B57-specific CD4 + T-cell responses were observed in patients alloimmunized against HLA-B57. Following specific stimulation, the patients presented HLA-specific CD4 + T cells producing tumor necrosis factor-α, interleukin (IL)-13, IL-17A, IL-2, IL-10, and IL-21. Conclusion: These results shed light on posttransfusion class I anti-HLA alloimmunization mechanisms and constitute a first step toward developing new strategies for reducing refractoriness.

T his peripheral blood smear from a 12-year-old child, cytomegalovirus and Epstein-Barr virus negative, 2 months after allogeneic stem cell transplantation (AlloSCT) for acute myeloid leukemia with maturation, shows atypical lymphocytes (panel A; for both panels, original magnification 3100, May-Grünwald Giemsa stain). Laboratory studies showed 42% homogenous atypical lymphocytes in a post-AlloSCT leukopenia (1.6 3 10 9 /L). These cells show an irregular nuclear outline, a round nucleolus, moderately condensed chromatin, and a high nuclear-to-cytoplasmic ratio mimicking lymphoblastic cells (panel B). The forward scatter/side scatter/CD45 panel of the flow cytometric analysis shows 42% of cells located in the lymphocyte gate and no CD45 low cells corresponding to blasts. Lymphocyte immunophenotyping revealed an exclusive B-lineage profile of CD1911 with polyclonal expression of surface immunoglobulin, typical of transitional B cells.Transitional B cells are the first B-lymphoid cells detected 1.5 to 2 months after AlloSCT. The proportion of these cells, usually morphologically similar to mature B cells, gradually decreases while the mature B cells increase. This case of blast-like appearance in a young patient with AlloSCT highlights the fact that some transitional B cells can be morphologically confusing with blasts, especially when the initial diagnostic is an acute lymphoid leukemia. Flow cytometry is the best option to differentiate between those 2 immature cells.For additional images, visit the ASH IMAGE BANK, a reference and teaching tool that is continually updated with new atlas and case study images. For more information visit http://imagebank.hematology.org.

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