HLA Loss - An Immune Escape Mechanism of Leukemic Cells

Following haploidentical HSCT, genomic loss of the mismatched HLA haplotype occurs in an average of 33% of post-HSCT patients (Crucitti et al., Leukemia, 2015) due to selective pressure of donor-derived T cells. Loss of HLA heterozygosity confers a selective advantage for leukemic cells that become able to evade the T cell-mediated immune surveillance. This event is sufficient to allow relapse of leukemia.

HLA MARKERS AND NON HLA MARKERS YIELD CONCORDANT RESULTS IN CLASSICAL RELAPSES AND DISCORDANT RESULTS IN HLA LOSS RELAPSES. ADAPTED FROM AHCI ET AL., BLOOD, 2017 — HLA MARKERS AND NON HLA MARKERS YIELD CONCORDANT RESULTS IN CLASSICAL RELAPSES AND DISCORDANT RESULTS IN HLA LOSS RELAPSES. ADAPTED FROM AHCI *ET AL*., BLOOD, 2017

Monitoring of HLA Loss Events Indicates Relapse Before its Actual Onset

Detecting increased mixed chimerism (gradual increase in the proportion of recipient cells) in patients after haploidentical HSCT
is based on comparative evaluation of the presence of HLA
and non HLA markers in bone marrow DNA samples. Results of these tests can provide guidance for rapid clinical decision-making
and choice of intensive salvage treatment.

HLA TRACE™ Assays Represent a Sensitive Solution for HLA Chimerism Monitoring After HSCT

Filling a gap in the scientific and diagnostic follow-up of allogeneic HSCT, the HLA TRACE™ Assays allow to indicate rapidly imminent post-HSCT HLA loss events before the onset of a relapse via quantitative polymerase chain reaction (qPCR). Alternatively, in combination with the more sensitive digital PCR (dPCR) methodology, the HLA TRACE™ Assays enable for a highly accurate and precise chimerism quantification that may form the basis for optimising patient-tailored therapy.