M M Jöris1, A C Lankester2, P A von dem Borne3, J Kuball4, M Bierings5, J J Cornelissen6, M E Groenendijk- Sijnke7, B van der Holt7, J J van Rood8, M Oudshoorn8, F H J Claas9. 1. Europdonor Foundation, The Netherlands; Department of Immunohematology and Blood transfusion, LUMC, The Netherlands. Electronic address: joris@europdonor.nl. 2. Department of Pediatrics, LUMC, The Netherlands. 3. Department of Hematology, LUMC, The Netherlands. 4. Department of Hematology and Immunology, UMCU, The Netherlands. 5. Wilhelmina Children's Hospital, UMCU, The Netherlands. 6. Department of Hematology, Erasmus MC-Daniel den Hoed, The Netherlands. 7. HOVON Data Center, Erasmus MC-Daniel den Hoed, The Netherlands. 8. Europdonor Foundation, The Netherlands; Department of Immunohematology and Blood transfusion, LUMC, The Netherlands. 9. Department of Immunohematology and Blood transfusion, LUMC, The Netherlands.
Abstract
INTRODUCTION: Previously we developed a weighted amino acid (AA) mismatch score predictive for cytotoxic T cell (CTL) alloreactivity (in vitro CTLp assay) based on the structure of the HLA class I molecule. The aim of this study is to confirm the clinical relevance of the CTLp assay and to validate the AA mismatch score as an alternative and easy to use tool to predict permissible mismatches in hematopoietic stem cell transplantation (HSCT). METHODS: We selected patients transplanted with a 9/10 single HLA class I mismatched graft (n=171) at three Dutch HSCT centers. A CTLp assay was performed in 73 donor-recipient pairs. As a control we selected 168 10/10 HLA matched pairs that were matched to the 9/10 single HLA class I mismatched pairs for HSCT year, donor type, patient age and diagnosis. RESULTS: We observed that pairs with negative a CTLp assay had statistically significant decreased incidence of mortality after HSCT comparable to that of 10/10 HLA matched pairs. However, the weighted AA mismatch score did not significantly predict any HSCT end point of interest. CONCLUSION: Further investigation is needed to unravel the mechanisms involved in causing the beneficial effect of a negative CTLp assay, before other alternative tools to predict HSCT outcome may be developed.
INTRODUCTION: Previously we developed a weighted amino acid (AA) mismatch score predictive for cytotoxic T cell (CTL) alloreactivity (in vitro CTLp assay) based on the structure of the HLA class I molecule. The aim of this study is to confirm the clinical relevance of the CTLp assay and to validate the AA mismatch score as an alternative and easy to use tool to predict permissible mismatches in hematopoietic stem cell transplantation (HSCT). METHODS: We selected patients transplanted with a 9/10 single HLA class I mismatched graft (n=171) at three Dutch HSCT centers. A CTLp assay was performed in 73 donor-recipient pairs. As a control we selected 168 10/10 HLA matched pairs that were matched to the 9/10 single HLA class I mismatched pairs for HSCT year, donor type, patient age and diagnosis. RESULTS: We observed that pairs with negative a CTLp assay had statistically significant decreased incidence of mortality after HSCT comparable to that of 10/10 HLA matched pairs. However, the weighted AA mismatch score did not significantly predict any HSCT end point of interest. CONCLUSION: Further investigation is needed to unravel the mechanisms involved in causing the beneficial effect of a negative CTLp assay, before other alternative tools to predict HSCT outcome may be developed.
Authors: V Kosmoliaptsis; M M Jöris; D H Mallon; A C Lankester; P A von dem Borne; J Kuball; M Bierings; J J Cornelissen; M E Groenendijk-Sijnke; B van der Holt; J A Bradley; M Oudshoorn; J J van Rood; C J Taylor; F H J Claas Journal: Bone Marrow Transplant Date: 2015-01-26 Impact factor: 5.483
Authors: K Fleischhauer; K W Ahn; H L Wang; L Zito; P Crivello; C Müller; M Verneris; B E Shaw; J Pidala; M Oudshorn; S J Lee; S R Spellman Journal: Bone Marrow Transplant Date: 2017-06-05 Impact factor: 5.483
Authors: Esteban Arrieta-Bolaños; Pietro Crivello; Bronwen E Shaw; Kwang Woo Ahn; Hai-Lin Wang; Michael R Verneris; Katharine C Hsu; Joseph Pidala; Stephanie J Lee; Katharina Fleischhauer; Stephen R Spellman Journal: Blood Adv Date: 2018-07-24
Authors: Moshe Israeli; Dave L Roelen; Mary Carrington; Effie Wang Petersdorf; Frans H J Claas; Geert W Haasnoot; Machteld Oudshoorn Journal: Front Immunol Date: 2014-10-27 Impact factor: 7.561
Authors: Esteban Arrieta-Bolaños; Pietro Crivello; Maximilian Metzing; Thuja Meurer; Müberra Ahci; Julie Rytlewski; Marissa Vignali; Erik Yusko; Peter van Balen; Peter A Horn; J H Frederik Falkenburg; Katharina Fleischhauer Journal: Front Immunol Date: 2018-02-19 Impact factor: 7.561