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

Piyanuch Kongtim¹  Janet Wood³  Qing Ma⁴  Dan Li⁴  Jun Zou⁵  Kai Cao⁵  Yudith Carmazzi⁵  Richard E. Champlin⁶  Supawee Saengboon⁶  Elizabeth J. Shpall⁶  Gabriela Rondon⁶  Rima M. Saliba⁶  Samer A. Srour⁶  Katayoun Rezvani⁶  Amin M. Alousi⁶  Stefan O. Ciurea⁷  Uri Greenbaum⁸  Michael Moller⁹ 

[1] Center of Excellence in Applied Epidemiology, Faculty of Medicine, Thammasat University, Pathumthani, Thailand;Department of Hematology, Soroka University Medical Center, Beer Sheva, Israel;Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States;Department of Hematopoietic Biology and Malignancy, The University of Texas MD Anderson Cancer Center, Houston, TX, United States;Department of Laboratory Medicine, Division of Pathology/Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States;Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, United States;Division of Hematology/Oncology, Department of Medicine, Chao Family Comprehensive Cancer Center, University of California, Irvine, CA, United States;Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel;School of Health Professions, The University of Texas MD Anderson Cancer Center, Houston, TX, United States;

关键词: signal regulatory protein alpha;    mismatch;    relapse protection;    cGVHD;    HSCT;    lymphoid malignancies;   

DOI  :  10.3389/fimmu.2022.904718

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown