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148-P HLA-E polymorphisms in hematopoietic stem cell transplantation
Abstracts
S113
147-P
PLATELET DIFFERENTIATION FROM CD34⫹ PROGENITOR CELLS IS INHIBITED BY SEMAPHORIN 7A. Yarúa Jaimes, Christiane Gras, Stephan Immenschuh, Rainer Blasczyk, Constanca Figueiredo. Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany. Aim: Thrombocytopenia is a common side effect in patients after high dose chemotherapy. New treatments for thrombocytopenia focus on the transfusion of ex vivo CD34⫹ cell derived-megakaryocytes (MKs). We observed that 50% of the patients that underwent chemotherapy upregulated the expression of Semaphorin7A (Sema7A), a signalling molecule involved in immunomodulation. We studied the effect of Sema7A in the differentiation and function of platelets (PLTs) derived from CD34⫹ progenitor cells. Methods: Recombinant Sema7A was used to stimulate CD34⫹ cell-derived MKs or PLTs. For PLT differentiation, CD34⫹ cells were isolated from G-CSF mobilized patients and incubated with thrombopoietin and interleukin-3 during 25 days in presence or absence of Sema7A. Expression of CD41, CD61 and CD42a was used to assess the MK and PLT differentiation via flow cytometry. The effect of the Sema7A cytokine secretion profile of MKs was measured using multiplex bead technology. Cell density and morphology during MK differentiation was assessed by fluorescence microscopy. Results: In presence of Sema7A, we observed that only 30% of the cell populations expressed the MK and PLT markers CD41, CD61 and CD42a in comparison to 70% of the cell populations when incubated in absence of the molecule. Moreover, a significant higher concentration of the pro-inflammatory cytokines IL-6 (245⫾67pg/ml, p⬍0.05) and IL-8 (10925⫾2254pg/ml, p⬍0.05) was secreted by MKs and PLTs exposed to Sema7A in comparison to the concentrations detected when the cells were differentiated in the absence of Sema7A (59⫾35pg/ml and 801⫾117pg/ml, respectively). Also, the MK cell density was up to 40% lower in presence of Sema7A compared to the cell density obtained in the absence of Sema7A. Conclusions: This data shows that Sema7A is a strong inhibitor of MK and PLT differentiation from CD34⫹ cells and offers new therapeutic approaches to face thrombocytopenia.
148-P
HLA-E POLYMORPHISMS IN HEMATOPOIETIC STEM CELL TRANSPLANTATION. Daniel Fu¨rst,1 Jovana Bindja,1 Renate Arnold,2 Wolfgang Herr,3 Schwerdtfeger Rainer,4 Carl-Heinz Mueller,5 Kirsten Recker,1 Schrezenmeier Hubert,1 Mytilineos Joannis.1 1Transplantation Immunology, Institute for Clinical Transfusion Medicine and Immunogenetics, Ulm, Germany; 2Hematology/Oncology Department, Charité Campus Virchow Berlin, Berlin, Germany; 3Hematology/Oncology Department, University Medical Center of Johannes Gutenberg University, Mainz, Germany; 4Hematology/Oncology Department, Stiftung DKD GmbH Wiesbaden, Wiesbaden, Germany; 5ZKRD - Zentrales Knochenmarkspender-Register fu¨r Deutschland, German National Bone Marrow Donor Registry, Ulm, Germany. Aim: HLA-E is an inhibitory ligand of natural killer cells and ␥/␦-T-cells. Differential expression of HLA-E alleles on the cell surface has been reported to influence outcome of hematopoietic stem cell transplantation (HSCT). Methods: We typed 116 10/10 (HLA-A,B,C,DR,DQ) high resolution matched patients (transplanted between 1997 and 2002) and their unrelated donors by PCR-SSP typing as described by Grimsley et al. The impact of HLA-E genotypes on patient overall-survival (OS), disease-free-survival (DFS) as well as cumulative incidences for relapse, transplant-related-mortality (TRM) and acute Graft versus Host Disease (aGvHD) was assessed. Results: Univariate analysis of OS and DFS showed no significant benefit of HLA-E matched vs mismatched pairs (Log Rank p⫽0.748 and p⫽0.848 respectively). Competing risk analysis showed not significant difference of incidence for relapse in the HLA-E matched vs mismatched group (36.6% vs 30.6% respectively; p⫽0.507). Overall incidence of TRM in HLA-E matched patients was 28.1% and 29.7% in the HLA-E mismatched group (p⫽0.945). The overall incidence of aGvHD in the HLA-E matched patient group was 42.3% vs 40.5% in the mismatched transplants (p⫽0.698). Conclusions: We could not find an association of HLA-E polymorphisms with outcomes of hematopoietic stem cell transplantation. Larger studies and better characterized cohorts are needed to conclusively address the issue of HLA-E in hematopoietic stem cell transplantation.
149-P
HISTORICAL BE THE MATCH REGISTRY HLA MATCH RATES FOR ADULT DONOR AND CORD BLOOD UNITS (CBU) FROM THE INCEPTION OF THE REGISTRY. Martin Maiers, Dennis Confer, Loren Gragert, Eric Williams, John Freeman. Bioinformatics Research, National Marrow Donor Program, Minneapolis, USA.
S113
147-P
PLATELET DIFFERENTIATION FROM CD34⫹ PROGENITOR CELLS IS INHIBITED BY SEMAPHORIN 7A. Yarúa Jaimes, Christiane Gras, Stephan Immenschuh, Rainer Blasczyk, Constanca Figueiredo. Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany. Aim: Thrombocytopenia is a common side effect in patients after high dose chemotherapy. New treatments for thrombocytopenia focus on the transfusion of ex vivo CD34⫹ cell derived-megakaryocytes (MKs). We observed that 50% of the patients that underwent chemotherapy upregulated the expression of Semaphorin7A (Sema7A), a signalling molecule involved in immunomodulation. We studied the effect of Sema7A in the differentiation and function of platelets (PLTs) derived from CD34⫹ progenitor cells. Methods: Recombinant Sema7A was used to stimulate CD34⫹ cell-derived MKs or PLTs. For PLT differentiation, CD34⫹ cells were isolated from G-CSF mobilized patients and incubated with thrombopoietin and interleukin-3 during 25 days in presence or absence of Sema7A. Expression of CD41, CD61 and CD42a was used to assess the MK and PLT differentiation via flow cytometry. The effect of the Sema7A cytokine secretion profile of MKs was measured using multiplex bead technology. Cell density and morphology during MK differentiation was assessed by fluorescence microscopy. Results: In presence of Sema7A, we observed that only 30% of the cell populations expressed the MK and PLT markers CD41, CD61 and CD42a in comparison to 70% of the cell populations when incubated in absence of the molecule. Moreover, a significant higher concentration of the pro-inflammatory cytokines IL-6 (245⫾67pg/ml, p⬍0.05) and IL-8 (10925⫾2254pg/ml, p⬍0.05) was secreted by MKs and PLTs exposed to Sema7A in comparison to the concentrations detected when the cells were differentiated in the absence of Sema7A (59⫾35pg/ml and 801⫾117pg/ml, respectively). Also, the MK cell density was up to 40% lower in presence of Sema7A compared to the cell density obtained in the absence of Sema7A. Conclusions: This data shows that Sema7A is a strong inhibitor of MK and PLT differentiation from CD34⫹ cells and offers new therapeutic approaches to face thrombocytopenia.
148-P
HLA-E POLYMORPHISMS IN HEMATOPOIETIC STEM CELL TRANSPLANTATION. Daniel Fu¨rst,1 Jovana Bindja,1 Renate Arnold,2 Wolfgang Herr,3 Schwerdtfeger Rainer,4 Carl-Heinz Mueller,5 Kirsten Recker,1 Schrezenmeier Hubert,1 Mytilineos Joannis.1 1Transplantation Immunology, Institute for Clinical Transfusion Medicine and Immunogenetics, Ulm, Germany; 2Hematology/Oncology Department, Charité Campus Virchow Berlin, Berlin, Germany; 3Hematology/Oncology Department, University Medical Center of Johannes Gutenberg University, Mainz, Germany; 4Hematology/Oncology Department, Stiftung DKD GmbH Wiesbaden, Wiesbaden, Germany; 5ZKRD - Zentrales Knochenmarkspender-Register fu¨r Deutschland, German National Bone Marrow Donor Registry, Ulm, Germany. Aim: HLA-E is an inhibitory ligand of natural killer cells and ␥/␦-T-cells. Differential expression of HLA-E alleles on the cell surface has been reported to influence outcome of hematopoietic stem cell transplantation (HSCT). Methods: We typed 116 10/10 (HLA-A,B,C,DR,DQ) high resolution matched patients (transplanted between 1997 and 2002) and their unrelated donors by PCR-SSP typing as described by Grimsley et al. The impact of HLA-E genotypes on patient overall-survival (OS), disease-free-survival (DFS) as well as cumulative incidences for relapse, transplant-related-mortality (TRM) and acute Graft versus Host Disease (aGvHD) was assessed. Results: Univariate analysis of OS and DFS showed no significant benefit of HLA-E matched vs mismatched pairs (Log Rank p⫽0.748 and p⫽0.848 respectively). Competing risk analysis showed not significant difference of incidence for relapse in the HLA-E matched vs mismatched group (36.6% vs 30.6% respectively; p⫽0.507). Overall incidence of TRM in HLA-E matched patients was 28.1% and 29.7% in the HLA-E mismatched group (p⫽0.945). The overall incidence of aGvHD in the HLA-E matched patient group was 42.3% vs 40.5% in the mismatched transplants (p⫽0.698). Conclusions: We could not find an association of HLA-E polymorphisms with outcomes of hematopoietic stem cell transplantation. Larger studies and better characterized cohorts are needed to conclusively address the issue of HLA-E in hematopoietic stem cell transplantation.
149-P
HISTORICAL BE THE MATCH REGISTRY HLA MATCH RATES FOR ADULT DONOR AND CORD BLOOD UNITS (CBU) FROM THE INCEPTION OF THE REGISTRY. Martin Maiers, Dennis Confer, Loren Gragert, Eric Williams, John Freeman. Bioinformatics Research, National Marrow Donor Program, Minneapolis, USA.