Justin Wahlstrom1, Kiran Patel2, Erik Eckhert3, Denice Kong4, Biljana Horn2, Morton J Cowan2, Christopher C Dvorak2. 1. Department of Pediatrics, Division of Pediatric Allergy, Immunology, & Bone Marrow Transplantation, University of California, San Francisco, Calif. Electronic address: Justin.wahlstrom@ucsf.edu. 2. Department of Pediatrics, Division of Pediatric Allergy, Immunology, & Bone Marrow Transplantation, University of California, San Francisco, Calif. 3. University of California San Francisco/University of California Berkeley Joint Medical Program, San Francisco, Calif. 4. Department of Surgery, Immunogenetics and Transplantation Laboratory, University of California, San Francisco, Calif.
Abstract
BACKGROUND: Graft-versus-host disease (GVHD) is a complication of allogeneic hematopoietic stem cell transplantation (HSCT). Transplacental maternal engraftment (TME), the presence of maternal T cells in peripheral blood before transplantation, is detectable in a significant proportion of patients with severe combined immunodeficiency (SCID). Although the presence of TME is associated with a decreased risk of rejecting a maternal graft, it is unknown whether TME plays a role in development of GVHD after HSCT. OBJECTIVE: The purpose of this study was to determine whether the presence of pretransplantation TME is associated with posttransplantation GVHD in patients with SCID. METHODS: This was an institutional retrospective review of 74 patients with SCID undergoing transplantation between 1988 and 2014. The incidence of acute graft-versus-host disease (aGVHD) was compared in patients with versus those without TME. Confounding variables, such as donor type and conditioning regimen, were included in a multivariate regression model. RESULTS: TME was identified in 35 of 74 children. Post-HSCT aGVHD developed with an incidence of 57.1% versus 17.9% in those without TME (P < .001). In univariate analysis donor type (mother) and GVHD prophylaxis (T-cell depletion) were also significant predictors of aGVHD. In multivariate analysis TME and chemotherapy conditioning were independent risk factors for the development of aGVHD (relative risk, 2.75, P = .006 and relative risk, 1.42, P = .02, respectively). CONCLUSION: TME independently predicts the development of posttransplantation aGVHD, even when controlling for donor type and conditioning used. The presence of TME should be considered when assessing the risk of aGVHD in patients with SCID and designing the approach for GVHD prophylaxis. Published by Elsevier Inc.
BACKGROUND:Graft-versus-host disease (GVHD) is a complication of allogeneic hematopoietic stem cell transplantation (HSCT). Transplacental maternal engraftment (TME), the presence of maternal T cells in peripheral blood before transplantation, is detectable in a significant proportion of patients with severe combined immunodeficiency (SCID). Although the presence of TME is associated with a decreased risk of rejecting a maternal graft, it is unknown whether TME plays a role in development of GVHD after HSCT. OBJECTIVE: The purpose of this study was to determine whether the presence of pretransplantation TME is associated with posttransplantation GVHD in patients with SCID. METHODS: This was an institutional retrospective review of 74 patients with SCID undergoing transplantation between 1988 and 2014. The incidence of acute graft-versus-host disease (aGVHD) was compared in patients with versus those without TME. Confounding variables, such as donor type and conditioning regimen, were included in a multivariate regression model. RESULTS:TME was identified in 35 of 74 children. Post-HSCT aGVHD developed with an incidence of 57.1% versus 17.9% in those without TME (P < .001). In univariate analysis donor type (mother) and GVHD prophylaxis (T-cell depletion) were also significant predictors of aGVHD. In multivariate analysis TME and chemotherapy conditioning were independent risk factors for the development of aGVHD (relative risk, 2.75, P = .006 and relative risk, 1.42, P = .02, respectively). CONCLUSION:TME independently predicts the development of posttransplantation aGVHD, even when controlling for donor type and conditioning used. The presence of TME should be considered when assessing the risk of aGVHD in patients with SCID and designing the approach for GVHD prophylaxis. Published by Elsevier Inc.
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