FALSE HOMOZYGOUS HLA GENOTYPING RESULTS DUE TO LOSS OF HETEROZYGOSITY IN ACQUIRED APLASTIC ANAEMIA.
(Abstract release date: 05/19/16)
EHA Library. Heyrman B. 06/09/16; 132554; E1005
Dr. Bert Heyrman
Contributions
Contributions
Abstract
Abstract: E1005
Type: Eposter Presentation
Background
The pathogenesis of acquired aplastic anaemia is driven by T cell-mediated destruction of hematopoietic progenitors. Clonal evolution is known to occur in around 70% of patients. This includes around 12% with loss of heterozygosity (LOH) of chromosome 6p, involving the human leukocyte antigen (HLA) locus. Loss or down-regulation of HLA class I antigens is a way to escape cytotoxic T-cell surveillance. LOH can appear even without previous therapy. In acquired aplastic anaemia it is well studied as a biological phenomenon. LOH appears to have no impact on the course of the disease nor does it predict response to treatment, as results are contradictory in this matter.
Aims
The aim of this case report is to draw attention on possible false HLA genotyping in acquired aplastic anaemia prior to allogeneic hematopoietic stem cell transplantation.
Methods
Repeated HLA genotyping was performed on peripheral blood using flow multiplex DNA typing and sequence-based typing.
Results
We report false HLA genotyping results due to loss of heterozygosity in a 59-year-old female patient of Caucasian origin, presenting with very severe aplastic anaemia. At diagnosis we obtained heterozygous results (A*24, A*33, B*07, B*14, C*07, C*08, DRB1*13, DRB1*15, DQB1*03, DQB1*06). Bone marrow karyotype was normal. After treatment with rabbit anti-thymocyte globulin + cyclosporine, not reaching a partial response at 6 months, we repeated HLA genotyping in order to search for an unrelated donor, because there was no HLA compatible sibling. This time we obtained homozygous results (A*24:02, B*07:02, C*07:02, DQ*06:02,DR*15.01). Repeated testing confirmed loss of HLA genotype heterozygosity. New bone marrow karyotype didn't show alterations in chromosome 6. Monosomy 7 was found, compatible with development of high risk myelodysplastic syndrome-associated cytogenetic abnormalities.
Conclusion
When homozygous HLA genotype results are obtained in acquired aplastic anemia, confirmatory testing on other somatic cells (eg. buccal swab) is needed to avoid hematopoietic stem cell transplantation with an unmatched donor.
Session topic: E-poster
Keyword(s): Aplastic anemia, HLA mismatched, LOH
Type: Eposter Presentation
Background
The pathogenesis of acquired aplastic anaemia is driven by T cell-mediated destruction of hematopoietic progenitors. Clonal evolution is known to occur in around 70% of patients. This includes around 12% with loss of heterozygosity (LOH) of chromosome 6p, involving the human leukocyte antigen (HLA) locus. Loss or down-regulation of HLA class I antigens is a way to escape cytotoxic T-cell surveillance. LOH can appear even without previous therapy. In acquired aplastic anaemia it is well studied as a biological phenomenon. LOH appears to have no impact on the course of the disease nor does it predict response to treatment, as results are contradictory in this matter.
Aims
The aim of this case report is to draw attention on possible false HLA genotyping in acquired aplastic anaemia prior to allogeneic hematopoietic stem cell transplantation.
Methods
Repeated HLA genotyping was performed on peripheral blood using flow multiplex DNA typing and sequence-based typing.
Results
We report false HLA genotyping results due to loss of heterozygosity in a 59-year-old female patient of Caucasian origin, presenting with very severe aplastic anaemia. At diagnosis we obtained heterozygous results (A*24, A*33, B*07, B*14, C*07, C*08, DRB1*13, DRB1*15, DQB1*03, DQB1*06). Bone marrow karyotype was normal. After treatment with rabbit anti-thymocyte globulin + cyclosporine, not reaching a partial response at 6 months, we repeated HLA genotyping in order to search for an unrelated donor, because there was no HLA compatible sibling. This time we obtained homozygous results (A*24:02, B*07:02, C*07:02, DQ*06:02,DR*15.01). Repeated testing confirmed loss of HLA genotype heterozygosity. New bone marrow karyotype didn't show alterations in chromosome 6. Monosomy 7 was found, compatible with development of high risk myelodysplastic syndrome-associated cytogenetic abnormalities.
Conclusion
When homozygous HLA genotype results are obtained in acquired aplastic anemia, confirmatory testing on other somatic cells (eg. buccal swab) is needed to avoid hematopoietic stem cell transplantation with an unmatched donor.
Session topic: E-poster
Keyword(s): Aplastic anemia, HLA mismatched, LOH
Abstract: E1005
Type: Eposter Presentation
Background
The pathogenesis of acquired aplastic anaemia is driven by T cell-mediated destruction of hematopoietic progenitors. Clonal evolution is known to occur in around 70% of patients. This includes around 12% with loss of heterozygosity (LOH) of chromosome 6p, involving the human leukocyte antigen (HLA) locus. Loss or down-regulation of HLA class I antigens is a way to escape cytotoxic T-cell surveillance. LOH can appear even without previous therapy. In acquired aplastic anaemia it is well studied as a biological phenomenon. LOH appears to have no impact on the course of the disease nor does it predict response to treatment, as results are contradictory in this matter.
Aims
The aim of this case report is to draw attention on possible false HLA genotyping in acquired aplastic anaemia prior to allogeneic hematopoietic stem cell transplantation.
Methods
Repeated HLA genotyping was performed on peripheral blood using flow multiplex DNA typing and sequence-based typing.
Results
We report false HLA genotyping results due to loss of heterozygosity in a 59-year-old female patient of Caucasian origin, presenting with very severe aplastic anaemia. At diagnosis we obtained heterozygous results (A*24, A*33, B*07, B*14, C*07, C*08, DRB1*13, DRB1*15, DQB1*03, DQB1*06). Bone marrow karyotype was normal. After treatment with rabbit anti-thymocyte globulin + cyclosporine, not reaching a partial response at 6 months, we repeated HLA genotyping in order to search for an unrelated donor, because there was no HLA compatible sibling. This time we obtained homozygous results (A*24:02, B*07:02, C*07:02, DQ*06:02,DR*15.01). Repeated testing confirmed loss of HLA genotype heterozygosity. New bone marrow karyotype didn't show alterations in chromosome 6. Monosomy 7 was found, compatible with development of high risk myelodysplastic syndrome-associated cytogenetic abnormalities.
Conclusion
When homozygous HLA genotype results are obtained in acquired aplastic anemia, confirmatory testing on other somatic cells (eg. buccal swab) is needed to avoid hematopoietic stem cell transplantation with an unmatched donor.
Session topic: E-poster
Keyword(s): Aplastic anemia, HLA mismatched, LOH
Type: Eposter Presentation
Background
The pathogenesis of acquired aplastic anaemia is driven by T cell-mediated destruction of hematopoietic progenitors. Clonal evolution is known to occur in around 70% of patients. This includes around 12% with loss of heterozygosity (LOH) of chromosome 6p, involving the human leukocyte antigen (HLA) locus. Loss or down-regulation of HLA class I antigens is a way to escape cytotoxic T-cell surveillance. LOH can appear even without previous therapy. In acquired aplastic anaemia it is well studied as a biological phenomenon. LOH appears to have no impact on the course of the disease nor does it predict response to treatment, as results are contradictory in this matter.
Aims
The aim of this case report is to draw attention on possible false HLA genotyping in acquired aplastic anaemia prior to allogeneic hematopoietic stem cell transplantation.
Methods
Repeated HLA genotyping was performed on peripheral blood using flow multiplex DNA typing and sequence-based typing.
Results
We report false HLA genotyping results due to loss of heterozygosity in a 59-year-old female patient of Caucasian origin, presenting with very severe aplastic anaemia. At diagnosis we obtained heterozygous results (A*24, A*33, B*07, B*14, C*07, C*08, DRB1*13, DRB1*15, DQB1*03, DQB1*06). Bone marrow karyotype was normal. After treatment with rabbit anti-thymocyte globulin + cyclosporine, not reaching a partial response at 6 months, we repeated HLA genotyping in order to search for an unrelated donor, because there was no HLA compatible sibling. This time we obtained homozygous results (A*24:02, B*07:02, C*07:02, DQ*06:02,DR*15.01). Repeated testing confirmed loss of HLA genotype heterozygosity. New bone marrow karyotype didn't show alterations in chromosome 6. Monosomy 7 was found, compatible with development of high risk myelodysplastic syndrome-associated cytogenetic abnormalities.
Conclusion
When homozygous HLA genotype results are obtained in acquired aplastic anemia, confirmatory testing on other somatic cells (eg. buccal swab) is needed to avoid hematopoietic stem cell transplantation with an unmatched donor.
Session topic: E-poster
Keyword(s): Aplastic anemia, HLA mismatched, LOH
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