engleski

DISEASE RELAPSE AND LOSS OF MISMATCHED HLA HAPLOTYPE IN HAPLOIDENTICAL STEM CELL TRANSPLANTATION

Relapse represents a frequent and severe complication after HSCT. In most cases relapse has recipient's origin and leads to status of mixed chimerism. However, in some cases it may be due to specific immune escape by leukemia via genomic loss of mismatched HLA haplotype. Aim of this study was to retrospectively analyze incidence of HLA loss in sixty patients transplanted with haploidentical donor at UHC Zagreb (2012-2019). Post HSCT chimerism status was monitored by qPCR. Mixed chimerism monitoring results identified 22 patients at higher risk for relapse, which was clinically confirmed for 12 (54.5%) of them. All 12 patients were tested for HLA loss using HLA typing by PCR-SSP. Patients were also tested by qPCR for 10 markers targeting some of the most frequent alleles of HLA-A, -C, and -DPB1 loci. HLA loss was detected in two patients. Patient 1 relapsed 6 years after HSCT, at which time chimerism monitoring detected 80% of patient cells. HLA typing revealed loss of patient’s mismatched allele at informative loci HLA-A, -B, - C. Patient 2 relapsed 5 months after HSCT, with chimerism monitoring result of 2% of patient cells. Loss of patient’s mismatched haplotype was detected at loci HLA-A and -DPB1. Ten patients relapsed without HLA loss with mixed chimerism monitoring results. In all cases PCR-SSP testing was successful in detecting mismatched patient alleles. The results suggests that PCR-SSP method is sufficiently sensitive and useful for detection of patient-specific HLA haplotype loss, providing clinically relevant information for relapse treatment even in cases with low level of patient cells in peripheral blood.

HLA loss ; haploidentical hematopoietic stem cell transplantation

nije evidentirano