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. 2016 Oct;30(10):2102-2106.
doi: 10.1038/leu.2016.144. Epub 2016 May 23.

Loss of the mismatched human leukocyte antigen haplotype in two acute myelogenous leukemia relapses after haploidentical bone marrow transplantation with post-transplantation cyclophosphamide

S R McCurdy  1 , B S Iglehart  2 , D A Batista  3 , C D Gocke  4 , Y Ning  5 , H A Knaus  1 , A M Jackson  2 , M S Leffell  2 , L Luznik  1 , I Gojo  1
Affiliations

Loss of the mismatched human leukocyte antigen haplotype in two acute myelogenous leukemia relapses after haploidentical bone marrow transplantation with post-transplantation cyclophosphamide

S R McCurdy et al. Leukemia. 2016 Oct.
No abstract available

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Figures

Figure 1
Figure 1. Assessment of patient-specific human leukocyte antigen (HLA)-haplotype loss on chromosome 6 using single nucleotide polymorphism array, reverse sequence specific oligonucleotide probe, and melting curve analysis in recipient 1
A) Profile of chromosome 6 in recipient 1. A schematic representation of chromosome 6 is included above the plots of single nucleotide polymorphism (SNP) array. Log R Ratio (red line average) at 0 indicates no copy number alteration and thus copy neutral loss of heterozygosity (CN-LOH) shown in the bracketed region. The wide range of B allele frequencies (blue tracks) represent the presence of both patient and donor alleles; B) Two reverse sequence specific oligonucleotide (rSSO) probes, HLA-A*26 (Probe #25) and HLADPB1 (Probe #8), were shown to be recipient-specific with low-level binding to the donor and decline in recipient-specific binding with serial dilutions of the recipient DNA with donor DNA. Posttransplantation relapse specimens of blood and marrow both show levels of Probe 25 consistent with donor samples, suggesting that the HLA-A was lost from the leukemic blasts. Similar results are shown with HLA-DPB1 Probe 8; C) Melting curve analysis of the dilution series shows its sensitivity in detecting the mismatched HLA-A*26 allele in the recipient diluted sample out to 14 cell equivalents. -dF/dT represents derivative of fluorescence over temperature; D) Melting curve analysis shows high pretransplant levels of HLA-A*26 DNA in the recipient, with no detection of HLA-A*26 in the donor sample. Posttransplant blood samples mirror that of the donor, reflecting loss of genomic HLA in the leukemic blasts at relapse. Bone Marrow specimens, however, showed a level of HLA-A*26 that is lower than the pretransplant recipient levels; E) Melting curve analysis on sorted leukemic blasts (defined as CD45low HLA-DR+) showed no HLA-A*26 DNA, supporting HLA loss.
Figure 2
Figure 2. Assessment of patient-specific mismatched human leukocyte antigen (HLA) - haplotype loss using single nucleotide polymorphism array and melting curve analysis in recipient 2
A) Karyotype of the diagnostic sample; B) Karyotype of the relapse sample showing a new finding of deletion in 6p; C) Single nucleotide polymorphism (SNP) array revealed the 15.9 Mb interstitial deletion (bracketed) that includes the HLA loci. The wide range of B allele frequencies (blue tracks) represent the presence of both patient and donor alleles; D) Melting curve analysis shows the ability to detect HLA-A*03 DNA in limited numbers of recipient pretransplant cells, but not in donor cells. -dF/dT represents derivative of fluorescence over temperature; E) Isolated leukemic CD45low CD33+ blasts from the recipient's peripheral blood and bone marrow show no detection of HLA-A*03 DNA, similar to that of the donor, suggesting loss of the recipient's mismatched HLA.
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