Loss of heterozygosity leading to incorrect HLA typing for platelet-transfusion refractory patient.

BACKGROUND: Management of platelet-transfusion refractory (PR) patients due to anti-HLA antibodies includes the provision of HLA-matched (HLAm) platelets (PLT) or PLTs that are negative for HLA antigens corresponding to the recipient antibodies. Obtaining HLAm PLTs is predicated on accurate HLA antigen typing of the recipient and donor. Here, we present the clinical implications of a case involving loss of heterozygosity (LOH) in a patient presented for PR workup. STUDY DESIGN AND METHODS: HLA typing was performed by three methods: (1) Real-time PCR; (2) Sequence-specific oligonucleotide (SSO) typing test; and (3) Next-Generation Sequencing (NGS). Cytogenomic SNP microarray was utilized to assess LOH. RESULTS: A 30-year-old female with newly diagnosed acute myelogenous leukemia was found to be PR secondary to HLA sensitization. A peripheral blood (PB) sample, containing 93% myeloid blast cells, was sent for HLA typing for the provision of HLAm PLTs. HLA typing revealed homozygosity at the HLA-A locus but was heterozygous at the -B and -C loci. After chemotherapy, HLA typing on a new PB sample, devoid of blast cells, identified HLA-A locus heterozygosity, which was subsequently confirmed by real-time PCR and NGS. Cytogenomic SNP microarray analysis demonstrated LOH of the HLA-A locus on chromosome 6p in the pretreatment sample but not in the posttreatment sample. CONCLUSION: In hematologic patients with high tumor burden, HLA homozygosity should be viewed with suspicion for potential LOH. Therefore, HLA testing should be repeated, preferably with a non-hematological source (e.g., buccal swab) or following successful reduction of the tumor burden.

Passenger Lymphocyte Syndrome; a Review of the Diagnosis, Treatment, and Proposed Detection Protocol.

Passenger lymphocyte syndrome (PLS) is caused by the transfer of B-lymphocytes present in the donor graft into the recipient circulation following solid organ or hematopoietic stem cell transplantation. These cells may produce antibodies against the recipient's red blood cells, thereby triggering antibody dependent cytotoxicity and erythroid clearance, with potential resulting hemolysis and jaundice. Although uncommon, the true incidence is unknown because many cases are subclinical, with only serologic findings or with non significant levels of hemolysis detectable clinically or by laboratory monitoring. Thus, these cases may not be detected in the immediate perioperative period. No standardized consensus exists on screening for PLS in patients. Through a review of the literature from 2009 to 2019, we aim to approximate the incidence of this condition in different solid organ transplant settings, as well as to streamline recognition, detection, and management of PLS early in the disease course to prevent adverse outcomes and minimize invasive therapy. The resultant literature review yielded 22 case reports and 8 case series comprising 71 solid organ transplant patients. Hematopoietic stem cell transplant cases were excluded, as PLS cases related to solid organ transplant were the primary focus of this review. Our institution has traditionally handled PLS on a case-by-case basis, although we hope to improve this process through an introduction of an algorithm based on review of the literature and formalized communication with primary caregivers.