Contributions
Abstract: PB1665
Type: Publication Only
Background
The impact of the bone marrow microenvironment on the behaviour of hematopoietic neoplasms is being increasingly studied. Human Leukocyte Antigen (HLA) Class II molecules play an essential role in presenting antigenic peptides to regulatory T-cells and in the generation of an immune response. HLA Class II molecules are expressed on acute myeloid leukemia (AML) blasts at diagnosis in most cases of non-M3 AML. The biological and clinical significance of HLA-DR antigen loss is not known.
Aims
We aimed to study a bone marrow lymphocyte profile (infiltrating lymphocytes) of HLA-DR negative non-M3 AML and possible association with bone marrow blast percentage and treatment outcome.
Methods
A total of 73 newly diagnosed patients with non-M3 AML admitted at National Cancer Institute Bratislava, Slovakia, between years 2012 and 2017 were included in this study. A diagnosis of AML was made based on the results of morphology, immunophenotype and genetics. An association between immunophenotypic characteristics of bone marrow blasts, bone marrow lymphocyte profile and blast percentage was evaluated by Kruskal-Wallis one-way ANOVA test, and for overall survival evaluation and response rate were used log-rank test and Fisher exact test, respectively, for multivariate analysis Cox regression and logistics regression models with AML genetic risk group, as appropriate.
Results
Patients were immunophenotypically characterized as HLA-DR positive (65 pts, 89%) or HLA-DR negative (8 pts, 11%). HLA-DR negativity was associated with CD11b negativity (100%) and CD34 negativity (62.5%). HLA-DR negative patients had significantly higher bone marrow blast percentages (median 92.2% vs. 63.3%, P = 0.005), lower bone marrow lymphocyte count (median 3.5% vs.8.0%, P = 0.01) and lower bone marrow T-lymphocyte count (median 2.5% vs. 6.8%, P = 0.007), with no significant difference in B-lymphocytes or NK-cells. Infections rate, overall survival and treatment response rate showed no significant differences between the HLA-DR negative and the HLA-DR positive group.
Conclusion
HLA-DR antigen loss is not frequent in myeloid leukemogenesis, and may represent mechanism of immune escape. HLA-DR negative AML cases have bone marrow lymphocyte profile distinguishable from those of typical AML, which needs further investigation. Understanding the role of the immune microenvironment in the behaviour of AML is of great importance, especially with the success of immunomodulatory treatment.
Session topic: 3. Acute myeloid leukemia - Biology & Translational Research
Keyword(s): Acute Myeloid Leukemia, Immunophenotype, Lymphocyte, MHC
Abstract: PB1665
Type: Publication Only
Background
The impact of the bone marrow microenvironment on the behaviour of hematopoietic neoplasms is being increasingly studied. Human Leukocyte Antigen (HLA) Class II molecules play an essential role in presenting antigenic peptides to regulatory T-cells and in the generation of an immune response. HLA Class II molecules are expressed on acute myeloid leukemia (AML) blasts at diagnosis in most cases of non-M3 AML. The biological and clinical significance of HLA-DR antigen loss is not known.
Aims
We aimed to study a bone marrow lymphocyte profile (infiltrating lymphocytes) of HLA-DR negative non-M3 AML and possible association with bone marrow blast percentage and treatment outcome.
Methods
A total of 73 newly diagnosed patients with non-M3 AML admitted at National Cancer Institute Bratislava, Slovakia, between years 2012 and 2017 were included in this study. A diagnosis of AML was made based on the results of morphology, immunophenotype and genetics. An association between immunophenotypic characteristics of bone marrow blasts, bone marrow lymphocyte profile and blast percentage was evaluated by Kruskal-Wallis one-way ANOVA test, and for overall survival evaluation and response rate were used log-rank test and Fisher exact test, respectively, for multivariate analysis Cox regression and logistics regression models with AML genetic risk group, as appropriate.
Results
Patients were immunophenotypically characterized as HLA-DR positive (65 pts, 89%) or HLA-DR negative (8 pts, 11%). HLA-DR negativity was associated with CD11b negativity (100%) and CD34 negativity (62.5%). HLA-DR negative patients had significantly higher bone marrow blast percentages (median 92.2% vs. 63.3%, P = 0.005), lower bone marrow lymphocyte count (median 3.5% vs.8.0%, P = 0.01) and lower bone marrow T-lymphocyte count (median 2.5% vs. 6.8%, P = 0.007), with no significant difference in B-lymphocytes or NK-cells. Infections rate, overall survival and treatment response rate showed no significant differences between the HLA-DR negative and the HLA-DR positive group.
Conclusion
HLA-DR antigen loss is not frequent in myeloid leukemogenesis, and may represent mechanism of immune escape. HLA-DR negative AML cases have bone marrow lymphocyte profile distinguishable from those of typical AML, which needs further investigation. Understanding the role of the immune microenvironment in the behaviour of AML is of great importance, especially with the success of immunomodulatory treatment.
Session topic: 3. Acute myeloid leukemia - Biology & Translational Research
Keyword(s): Acute Myeloid Leukemia, Immunophenotype, Lymphocyte, MHC