Ogden Regional Medical Center, Utah, United States
Background/Case Studies: Obtaining accurate human leukocyte antigen (HLA) typing of possible allogeneic stem cell transplant patients is critical to ensure successful transplantation and engraftment. A de novo acute myeloid leukemia (AML) patient demonstrated partial loss of heterozygosity (LOH) under elevated tumor burden and discordant HLA typing results.
Study
Design/Methods: HLA typing was performed by Next-Generation Sequencing for the patient and PCR sequence-specific oligonucleotide probes for familial testing. AML diagnostic testing included flow cytometry, fluorescence in situ hybridization, chromosome analysis, and bone marrow morphology. LOH was assessed with Cytogenomic SNP Microarray.
Results/Findings: A 36-year-old male patient with a history of oral, sinus, cellulitis, and pulmonary infections was diagnosed with de novo AML with stemline (sl) CBFB::MYH11 fusion inv(16) and trisomy 22, with two sidelines of sl plus del 7q31, and sl plus t(20:22). Admission testing showed Copy-Neutral Loss of Heterozygosity at 6p25.3p21.31, including the HLA locus. A peripheral blood (PB) sample was sent for HLA typing, with the patient’s PB absolute blast count at 4144/µL on the same collection date. HLA results showed LOH at loci -B, -C, and -DPB1, resulting in no matches in the national marrow donor program (NMDP) registry. Familial HLA typing revealed no matches for any half-siblings and the patient’s only biological child. The lack of an expected haploidentical match for the biological child resulted in the investigation of the patient’s initial HLA typing and discussion with HLA typing lab director, questioning the LOH and possible interference of blasts. Post induction therapy and two rounds of consolidation therapy, a PB sample devoid of blast cells and a buccal swab (BS) were collected for testing and both samples showed heterozygosity for all HLA loci. The biological child and one half-sibling were confirmed to be haploidentical matches, with two full matches identified in the NMDP registry. Conclusions: Altered expression of HLA antigens on the cell surface is more commonly reported in solid tumors than in hematologic malignancies. This case illustrates an example in a de novo AML patient with LOH detected as part of admission diagnostic testing, and further HLA homozygosity reported before investigation. The delay in finding an appropriate donor, including the expected haploidentical match with the biological child, caused psychosocial distress for the family who were originally told that the child was not a match and therefore not the patient’s biological child. All cases of LOH or HLA homozygosity should warrant further investigation, either testing from a non-hematologic source such as a BS, or PB devoid of blast cells after sufficient therapy.
