SIRPα Mismatch Is Associated With Relapse Protection and Chronic Graft-Versus-Host Disease After Related Hematopoietic Stem Cell Transplantation for Lymphoid Malignancies
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematologic malignancies. Alloreactivity after HSCT is known to be mediated by adaptive immune cells expressing rearranging receptors. Recent studies demonstrated that the innate immune system could...
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.904718/full |
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| author | Rima M. Saliba Samer A. Srour Uri Greenbaum Uri Greenbaum Qing Ma Yudith Carmazzi Michael Moller Janet Wood Stefan O. Ciurea Piyanuch Kongtim Piyanuch Kongtim Gabriela Rondon Dan Li Supawee Saengboon Amin M. Alousi Katayoun Rezvani Elizabeth J. Shpall Kai Cao Richard E. Champlin Jun Zou |
| author_facet | Rima M. Saliba Samer A. Srour Uri Greenbaum Uri Greenbaum Qing Ma Yudith Carmazzi Michael Moller Janet Wood Stefan O. Ciurea Piyanuch Kongtim Piyanuch Kongtim Gabriela Rondon Dan Li Supawee Saengboon Amin M. Alousi Katayoun Rezvani Elizabeth J. Shpall Kai Cao Richard E. Champlin Jun Zou |
| author_sort | Rima M. Saliba |
| collection | DOAJ |
| description | Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematologic malignancies. Alloreactivity after HSCT is known to be mediated by adaptive immune cells expressing rearranging receptors. Recent studies demonstrated that the innate immune system could likewise sense the non-self signals and subsequently enhance the alloimmune response. We recently demonstrated that the donor/recipient mismatch of signal regulatory protein α (SIRPα), an immunoglobulin receptor exclusively expressed on innate cells, is associated with a higher risk of cGVHD and relapse protection in a cohort of acute myeloid leukemia patients who underwent allo-HSCT. Whether these effects also occur in other hematologic malignancies remains unclear. In the present study, we compared outcomes by SIRPα match status in a cohort of 310 patients who received allo-HSCT from an HLA matched-related donor for the treatment of lymphoid malignancies. Multivariable analysis showed that SIRPα mismatch was associated with a significantly higher rate of cGVHD (hazard ratio [HR] 1.8, P= .002), cGVHD requiring systemic immunosuppressive therapy (HR 1.9, P= .005), a lower rate of disease progression (HR 0.5, P= .003) and improved progression-free survival (HR 0.5, P= .001). Notably, the effects of SIRPα mismatch were observed only in the patients who achieved >95% of donor T-cell chimerism. The mismatch in SIRPα is associated with favorable relapse protection and concurrently increased risk of cGVHD in patients who undergo allo-HSCT for lymphoid malignancies, and the optimal donor could be selected based on the finding of the study to mitigate the risk of GVHD and relapse. |
| first_indexed | 2024-04-13T14:39:54Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T14:39:54Z |
| publishDate | 2022-07-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-bc5c5e2f611f44f895dc64e8b88574172022-12-22T02:42:56ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.904718904718SIRPα Mismatch Is Associated With Relapse Protection and Chronic Graft-Versus-Host Disease After Related Hematopoietic Stem Cell Transplantation for Lymphoid MalignanciesRima M. Saliba0Samer A. Srour1Uri Greenbaum2Uri Greenbaum3Qing Ma4Yudith Carmazzi5Michael Moller6Janet Wood7Stefan O. Ciurea8Piyanuch Kongtim9Piyanuch Kongtim10Gabriela Rondon11Dan Li12Supawee Saengboon13Amin M. Alousi14Katayoun Rezvani15Elizabeth J. Shpall16Kai Cao17Richard E. Champlin18Jun Zou19Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Hematology, Soroka University Medical Center, Beer Sheva, IsraelFaculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, IsraelDepartment of Hematopoietic Biology and Malignancy, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Laboratory Medicine, Division of Pathology/Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesSchool of Health Professions, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDivision of Hematology/Oncology, Department of Medicine, Chao Family Comprehensive Cancer Center, University of California, Irvine, CA, United StatesDivision of Hematology/Oncology, Department of Medicine, Chao Family Comprehensive Cancer Center, University of California, Irvine, CA, United StatesCenter of Excellence in Applied Epidemiology, Faculty of Medicine, Thammasat University, Pathumthani, ThailandDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Hematopoietic Biology and Malignancy, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Laboratory Medicine, Division of Pathology/Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Laboratory Medicine, Division of Pathology/Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematologic malignancies. Alloreactivity after HSCT is known to be mediated by adaptive immune cells expressing rearranging receptors. Recent studies demonstrated that the innate immune system could likewise sense the non-self signals and subsequently enhance the alloimmune response. We recently demonstrated that the donor/recipient mismatch of signal regulatory protein α (SIRPα), an immunoglobulin receptor exclusively expressed on innate cells, is associated with a higher risk of cGVHD and relapse protection in a cohort of acute myeloid leukemia patients who underwent allo-HSCT. Whether these effects also occur in other hematologic malignancies remains unclear. In the present study, we compared outcomes by SIRPα match status in a cohort of 310 patients who received allo-HSCT from an HLA matched-related donor for the treatment of lymphoid malignancies. Multivariable analysis showed that SIRPα mismatch was associated with a significantly higher rate of cGVHD (hazard ratio [HR] 1.8, P= .002), cGVHD requiring systemic immunosuppressive therapy (HR 1.9, P= .005), a lower rate of disease progression (HR 0.5, P= .003) and improved progression-free survival (HR 0.5, P= .001). Notably, the effects of SIRPα mismatch were observed only in the patients who achieved >95% of donor T-cell chimerism. The mismatch in SIRPα is associated with favorable relapse protection and concurrently increased risk of cGVHD in patients who undergo allo-HSCT for lymphoid malignancies, and the optimal donor could be selected based on the finding of the study to mitigate the risk of GVHD and relapse.https://www.frontiersin.org/articles/10.3389/fimmu.2022.904718/fullsignal regulatory protein alphamismatchrelapse protectioncGVHDHSCTlymphoid malignancies |
| spellingShingle | Rima M. Saliba Samer A. Srour Uri Greenbaum Uri Greenbaum Qing Ma Yudith Carmazzi Michael Moller Janet Wood Stefan O. Ciurea Piyanuch Kongtim Piyanuch Kongtim Gabriela Rondon Dan Li Supawee Saengboon Amin M. Alousi Katayoun Rezvani Elizabeth J. Shpall Kai Cao Richard E. Champlin Jun Zou SIRPα Mismatch Is Associated With Relapse Protection and Chronic Graft-Versus-Host Disease After Related Hematopoietic Stem Cell Transplantation for Lymphoid Malignancies Frontiers in Immunology signal regulatory protein alpha mismatch relapse protection cGVHD HSCT lymphoid malignancies |
| title | SIRPα Mismatch Is Associated With Relapse Protection and Chronic Graft-Versus-Host Disease After Related Hematopoietic Stem Cell Transplantation for Lymphoid Malignancies |
| title_full | SIRPα Mismatch Is Associated With Relapse Protection and Chronic Graft-Versus-Host Disease After Related Hematopoietic Stem Cell Transplantation for Lymphoid Malignancies |
| title_fullStr | SIRPα Mismatch Is Associated With Relapse Protection and Chronic Graft-Versus-Host Disease After Related Hematopoietic Stem Cell Transplantation for Lymphoid Malignancies |
| title_full_unstemmed | SIRPα Mismatch Is Associated With Relapse Protection and Chronic Graft-Versus-Host Disease After Related Hematopoietic Stem Cell Transplantation for Lymphoid Malignancies |
| title_short | SIRPα Mismatch Is Associated With Relapse Protection and Chronic Graft-Versus-Host Disease After Related Hematopoietic Stem Cell Transplantation for Lymphoid Malignancies |
| title_sort | sirpα mismatch is associated with relapse protection and chronic graft versus host disease after related hematopoietic stem cell transplantation for lymphoid malignancies |
| topic | signal regulatory protein alpha mismatch relapse protection cGVHD HSCT lymphoid malignancies |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.904718/full |
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