P102 Proposed loss of heterozygosity of HLA class I region during acute myelogenous leukemia blast crisis

A 36 yo old male, newly diagnosed with AML, was accepted for transplant evaluation. Initial sequence based typing (SBT) of the patient revealed homozygous HLA class I alleles (Table 1). A potential related donor (sibling) typed by sequence specific oligonucleotide (SSO) primers shared one haplotype with the patient. A search identified a potential NMDP donor matching the patient at 10/10 antigens. However, confirmatory typing of the patient performed on a separate sample 106 days after diagnosis by SSO showed additional HLA A and B antigens and thus did not match the initial sample. HLA typing of the patient on new blood and buccal swab samples by STAT SSO matched the confirmatory typing, and revealed the sibling as a two haplotype match at the level tested. Additional analysis of short tandem repeats of the initial and confirmatory patient samples and initial sibling donor sample ruled out a sample swap originating within the laboratory. Consultation with the transplant team revealed the patient’s initial sample was drawn while the patient was experiencing blast crisis with myleoblasts representing 88% of the total cells. After one round of induction therapy, beginning 4 days after diagnosis, the patient achieved complete remission with a hypocellular bone marrow biopsy without excess blasts. In preparation for matched unrelated allogeneic stem cell transplant from the NMDP donor, the patient underwent consolidation therapy, and a bone marrow biopsy 98 days after initial diagnosis (8 days prior to confirmatory typing) showed the presence of all hematopoietic elements, an average cellularity of 65% and no excess blasts. Loss of heterozygosity in HLA Class I region of chromosome 6 is suspected in the patient’s initial sample and whole genome scanning by array comparative genomic hybridization is in process to confirm. The case study highlights the importance of confirmatory HLA typing for stem cell transplant patients and suggests that HLA typing of patients in blast crisis should be performed by buccal swab instead of blood. Download high-res image (317KB) Download full-size image