Blood immunology & cellular therapy.最新文献

{"title":"Glucocorticoid-induced TNF receptor ligand-dependent B-cell expansion of regulatory T cells as an immune cell therapy strategy.","authors":"Cody J Gurski, Mohamed Khalil, Kelli C Sommers, Angela K Beltrame, Bonnie N Dittel","doi":"10.1016/j.bict.2026.100065","DOIUrl":"https://doi.org/10.1016/j.bict.2026.100065","url":null,"abstract":"<p><p>B-cell-based immune cell therapies represent a potential strategy for restoring immune tolerance by expanding regulatory T cells (Tregs). CD4⁺Foxp3⁺ Tregs are essential for maintaining immune homeostasis and represent an attractive therapeutic target. However, clinically established strategies to safely and durably expand endogenous Tregs remain lacking. We previously identified IgD^low/- B cells as a splenic B-cell subset that promotes Treg expansion through a glucocorticoid-induced TNF receptor ligand (GITRL)-dependent mechanism, whereas other B cell populations do not. In B-cell-specific GITRL transgenic mice, Treg numbers are significantly increased, and the severity of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, is attenuated. To evaluate the translational potential of this pathway as a hematopoietic immune cell therapy, we transplanted wild-type recipients with bone marrow from GITRL transgenic donors. After hematopoietic reconstitution, GITRL expression was selectively increased on B cells. This resulted in the expansion of endogenous Tregs and a corresponding increase in the proportion of Tregs within the CD4⁺ T-cell compartment, with near-complete suppression of EAE. These findings demonstrate that enhancing GITRL expression within the hematopoietic B-cell compartment provides a tractable strategy for expanding endogenous Tregs and augmenting Treg-mediated immune suppression, establishing a framework for developing B-cell-based immune cell therapies capable of durable immune suppression for inflammatory diseases.</p>","PeriodicalId":520924,"journal":{"name":"Blood immunology & cellular therapy.","volume":"2 3","pages":"100065"},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"B7-H3 expression impacts outcomes in myeloma and is targetable with an NK cell engager.","authors":"Aimee M Merino, Bartosz Grzywacz, Hayden Hamsher, Young Vue, Hazel Reilly, Benjamin Miller, Petra Krhovska, Colleen Forster, Zachary Davis, Laura Bendzick, Megan Weivoda, Neha Sharma, Anders Narum, Ryan Shanley, Martin Felices, Nicholas A Zorko, Evren Alici, Jeffrey S Miller","doi":"10.1016/j.bict.2026.100069","DOIUrl":"10.1016/j.bict.2026.100069","url":null,"abstract":"<p><p>B7-H3 acts as a checkpoint inhibitor, influences the tumor microenvironment, and is necessary for osteoclast (OC) development. Given its dual roles in promoting cancer survival and bone breakdown, we looked at its expression pattern in >200 multiple myeloma (MM) patients and association with cytogenetic abnormalities and outcomes. We found that most newly diagnosed patients had B7-H3⁺ plasma cells or stroma regardless of cytogenetic risk and expression on plasma cells increased with subsequent relapses. In marrow aspirates and core biopsies we identified B7-H3⁺ myeloid derived suppressor cells (MDSC) and (OC). We found that high B7-H3 expression was associated with pathologic fractures, bone lesions, and worse progression free survival (PFS). To confirm the utility of B7-H3 as a target in MM, we tested a tri-specific killer engager (TriKE) that binds CD16 on natural killer (NK) cells and B7-H3 while also delivering a recombinant IL-15 molecule to promote NK cell activity. The B7-H3 TriKE restored the ability of patient-derived NK cells to recognize and kill MM and enhanced NK cell-mediated killing of tumor, MDSC, OCs, and fibroblasts. These data suggest that targeting B7-H3 may positively impact outcomes and prevent the development of new bone lesions. In addition to its ability to directly target MM and immunosuppressive cells in the tumor microenvironment, the B7-H3 TriKE improved cytokine secretion and polyfunctionality of NK cells in a single cell assay. These findings advance our understanding of B7-H3's role in MM pathogenesis and validate the use of the B7-H3 TriKE to improve therapeutic outcomes in MM.</p>","PeriodicalId":520924,"journal":{"name":"Blood immunology & cellular therapy.","volume":"2 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13645307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149140315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic steroid treatment of grade I acute GVHD increases steroid-refractory GVHD and NRM.","authors":"Yu Akahoshi, Nikolaos Katsivelos, Ioannis E Louloudis, Daniela Weber, Francis Ayuk, William J Hogan, Yi-Bin Chen, Aaron M Etra, Paibel Aguayo-Hiraldo, Chantiya Chanswangphuwana, Hannah K Choe, Elizabeth O Hexner, Carrie L Kitko, Monzr M Al Malki, Pietro Merli, Timothy S Olson, Muna Qayed, Ingrid Vasova, Matthias Wölfl, Janna Baez, Gilbert Eng, Sigrun Gleich, George Morales, Nikolaos Spyrou, Rachel Young, Marcio Diniz, Ryotaro Nakamura, John E Levine, James L M Ferrara","doi":"10.1016/j.bict.2026.100044","DOIUrl":"10.1016/j.bict.2026.100044","url":null,"abstract":"<p><p>The use of systemic corticosteroids is recommended only for grades II to IV acute graft-versus-host disease (GVHD), but many patients are often treated at the onset of grade I in real-world practice. We retrospectively analyzed outcomes of 1143 patients with grade I GVHD from 24 Mount Sinai Acute GVHD International Consortium (MAGIC) transplant centers. Approximately half received \"up-front\" systemic steroids, whereas the remainder received topical steroids alone; GVHD progressed to grade II to IV in only one-third of these patients. Up-front steroids decreased the risk for grade II to IV GVHD but not grade III to IV acute GVHD or the need for a second line of treatment. Systemic steroids were equally effective at treating grade I or II GVHD; however, up-front therapy exposed 3 times more patients to systemic steroids, with a corresponding threefold increase in GVHD that required additional therapy and a threefold rise in infection-related deaths. In multivariable analyses, up-front steroids were significantly associated with higher nonrelapse mortality (NRM; <i>P</i> = .026). MAGIC biomarkers identified most patients with grade I GVHD as low risk and unlikely to progress to severe GVHD regardless of treatment. Nevertheless, low-risk patients who received up-front steroids experienced a threefold increase in infectious deaths compared with those treated topically. This study supports the consensus recommendation of topical therapy for patients with low-risk grade I GVHD, a strategy that can be supported by biomarkers to avoid unnecessary steroid exposure and increased NRM.</p>","PeriodicalId":520924,"journal":{"name":"Blood immunology & cellular therapy.","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13169643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Donor lymphocyte infusion as immune modulation after pediatric allogeneic transplantation.","authors":"Dimitrios Filioglou, Richard J Simpson, Emmanuel Katsanis","doi":"10.1016/j.bict.2026.100055","DOIUrl":"10.1016/j.bict.2026.100055","url":null,"abstract":"<p><p>Relapse remains a leading cause of failure after allogeneic hematopoietic cell transplantation for pediatric hematologic malignancies. Donor lymphocyte infusion (DLI) offers a uniquely accessible and scalable form of nonengineered adoptive cellular therapy. Although historically viewed as salvage therapy, emerging data support a paradigm shift toward using DLI as strategic immune modulation rather than rescue. This review synthesizes the biological rationale and clinical evidence for DLI in children, integrating the adult data when necessary to define translatable principles. Across platforms, outcomes rely on timing, disease burden, and the immune context. We highlight the superiority of prophylactic and preemptive DLI over therapeutic use and review contemporary structured approaches relying on treatment initiation at low and safe doses and escalation based on strict tolerance and monitoring criteria. Special consideration is given to haploidentical transplantation and mechanisms of immune escape such as HLA loss that limit T-cell-based interventions. Furthermore, we examine emerging combinations, including DLI with blinatumomab in B-cell acute lymphoblastic leukemia and hypomethylating agents in myeloid malignancies. Finally, we discuss T-cell subset manipulation to mitigate graft-versus-host disease while preserving the graft-versus-leukemia effects. All these data support a modern framework for pediatric DLI that prioritizes early, biology-informed interventions and rational combinations, underscoring the urgent need for pediatric-specific prospective studies.</p>","PeriodicalId":520924,"journal":{"name":"Blood immunology & cellular therapy.","volume":"2 2","pages":"100055"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13552190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148915058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precision Editing of Cyclophilin A Generates Cyclosporine and Voclosporin Resistant Cellular Therapies.","authors":"Holly Wobma, Francesca Alvarez Calderon, Jiayi Dong, Kayleigh Omdahl, Xianliang Rui, Elisa J Rojas Palato, Rene S Bermea, Alexandre Albanese, Franziska Wachter, Marlana Winschel, Katherine A Michaelis, William A Burns, Gillian Selig, Lorenzo Cagnin, Victor Tkachev, Susan E Prockop, Peter A Nigrovic, Bruce R Blazar, Ulrike Gerdemann, Leslie S Kean","doi":"10.1016/j.bict.2026.100054","DOIUrl":"10.1016/j.bict.2026.100054","url":null,"abstract":"<p><p>Recipients of allogeneic transplants or patients with autoimmune disease require immune suppression, often with calcineurin inhibitors. There is an expanding repertoire of immune effector cell therapies, including CD19 CAR-T cells and viral-specific T cells, deployed in these patients; however, ongoing calcineurin inhibition may be detrimental to cell therapy function. We developed a CRISPR/Cas9-based approach to engineer dual cyclosporine/voclosporin resistant cell therapies by targeting <i>PPIA</i> (encoding cyclophilin A), a critical binding partner for both drugs. Because Cyclophilin A has homeostatic functions in T cells, a complete knock-out is detrimental to cell viability. We thus targeted its C-terminus, disrupting drug binding while leaving the majority of the protein intact. C-terminal editing was stable throughout expansion and preserved Cyclophilin A expression. Edited CD19 CAR-T cells retained effector function in the presence of cyclosporine and voclosporin, including proliferation, cytokine production, and target cell killing, resulting in improved survival in murine models of CD19+ leukemia. Edited CMV-specific T cells also demonstrated preserved antigen-specific proliferation and cytokine production in the presence of these drugs. C-terminal editing of Cyclophilin A offers a promising avenue for developing next-generation cell therapies for patients receiving calcineurin inhibitors.</p>","PeriodicalId":520924,"journal":{"name":"Blood immunology & cellular therapy.","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13681324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149241183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of an optimal absolute lymphocyte count at leukapheresis in patients with lymphoma treated with CART.","authors":"Kunhwa Kim, Zachary Hunzeker, Xiaowen Sun, Ryan Sun, Timothy Voorhees, Youssef Youssef, Narendranath Epperla, Michelly De Castro, Karla Ow, Minifrida Santiago, Jaimole Varghese, Amy Ayers, Jeremy Ramdial, Chitra Hosing, Partow Kebriaei, Elizabeth Shpall, Michael Jain, Julio Chavez, Frederick L Locke, Sattva S Neelapu, Sairah Ahmed, Paolo Strati","doi":"10.1016/j.bict.2026.100042","DOIUrl":"10.1016/j.bict.2026.100042","url":null,"abstract":"<p><p>T-cell fitness can be impaired in patients with large B-cell lymphoma (LBCL) planned for CART (chimeric antigen receptor T-cell therapy). Although absolute lymphocyte count (ALC) at the time of leukapheresis has been shown to associate with outcomes in patients with LBCL treated axicabtagene ciloleucel (axi-cel), no threshold has been identified. This is a multicenter retrospective study including 1 axi-cel training and validation cohort, and 1 mixed-product validation cohort. The change-point method was used to identify an ALC threshold associating with optimal progression-free survival (PFS). Three hundred seventy-nine patients were included in the axi-cel training cohort. ALC as a continuous variable was associated with complete response on day 30 (median, 0.79 × 10³/μL vs 0.63 × 10³/μL; <i>P</i> = .004). An ALC of 0.34 × 10³/μL was identified as the optimal threshold for PFS (7 vs 3 months; <i>P</i> = .0013). The association was confirmed in the axi-cel validation cohort (165 patients; 19.8 vs 3.5 months; <i>P</i> = .04) but not in the mixed validation cohort (163 patients; 5 vs 1.5 months; <i>P</i> = .3). On univariate analysis, characteristics associated with ALC above the threshold included low International Prognostic Index score (<i>P</i> = .02), low serum C-reactive protein level (<i>P</i> = .02), low serum ferritin level (<i>P</i> < .001), and low number of prior lines of systemic therapy (<i>P</i> = .02). An ALC of >0.34 × 10³/μL at the time of apheresis is associated with optimal outcomes in patients with LBCL treated with axi-cel. A deeper investigation of the impact of prior therapies on the number and phenotype of lymphocytes at time of apheresis is warranted.</p>","PeriodicalId":520924,"journal":{"name":"Blood immunology & cellular therapy.","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13340592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148407845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adenosine signaling promotes double-negative T-cell anticancer responses in conditions of CD8 T-cell lymphopenia.","authors":"Zhi Huang, Brionna King, Laura Naldi, Lucio Miele, Giulia Monticone","doi":"10.1016/j.bict.2026.100031","DOIUrl":"10.1016/j.bict.2026.100031","url":null,"abstract":"<p><p>CD8 T-cell lymphopenia is observed in a variety of conditions, and has been linked with poorer survival, and increased risk of developing cancer and infections. An increase in double-negative T cells (DNTs), a subset of T cells that lack CD8 and CD4 coreceptors, has been reported in both human patients with CD8 T-cell lymphopenia and mice depleted of CD8 T cells. Promoting the generation of immunoprotective DNTs could compensate for the lack of CD8 T cells in affected patients, but strategies to generate protective DNTs remain unclear. In this study, we found that it is possible to promote immunoprotective antitumor DNTs under conditions of CD8 T-cell lymphopenia using the antileukemic drug forodesine. This work could have significant therapeutic implications for patients with CD8 T-cell lymphopenia, including patients with cancer.</p>","PeriodicalId":520924,"journal":{"name":"Blood immunology & cellular therapy.","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13411137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148623863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Streptavidin-drug conjugates streamline optimization of antibody-based hematopoietic stem cell transplant conditioning.","authors":"Aditya R Yelamali, Ezhilarasi Chendamarai, Julie K Ritchey, Michael P Rettig, John F DiPersio, Stephen P Persaud","doi":"10.1016/j.bict.2025.100012","DOIUrl":"10.1016/j.bict.2025.100012","url":null,"abstract":"<p><p>Hematopoietic stem cell transplantation (HSCT) conditioning using antibody-drug conjugates (ADC) is a promising approach to preparing patients for transplant, potentially avoiding the severe toxicities of conventional chemotherapy- and irradiation-based conditioning regimens. The toxic payload determines the efficacy and potential toxicities of an ADC, but comparison of different payloads in conjugates designed for HSCT conditioning has not been reported. Such comparisons would be greatly facilitated by methods enabling efficient screening of many combinations of antibody and payload. Herein, we used Click chemistry to conjugate four different small molecule payloads to a streptavidin backbone, yielding streptavidin-drug conjugates that can be combined with any biotinylated antibody to rapidly and cost-effectively produce an ADC. We vetted this system by evaluating CD45-targeted ADCs, finding pyrrolobenzodiazepine (PBD) dimers to be the most effective payload of those we tested for targeting mouse and human hematopoietic stem cells (HSCs) and acute myeloid leukemia (AML) cells. Single-dose murine CD45-PBD enabled near-complete conversion to donor hematopoiesis in syngeneic HSCT models as well as in autologous transplantation using gene-edited HSCs. Finally, human CD45-PBD targeted human HSCs <i>in vivo</i> and provided significant antileukemia benefit in a patient-derived AML xenograft model. Notably, our streptavidin-drug conjugates were produced using routine molecular biology techniques and readily available supplies without requiring complex instrumentation, making production and screening of ADCs for myriad targeting applications accessible to virtually any laboratory.</p>","PeriodicalId":520924,"journal":{"name":"Blood immunology & cellular therapy.","volume":"1 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12823147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146032686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Viral vector-free generation of orthogonal IL-2-responsive CAR T cells through gene editing of IL-2 and its receptor.","authors":"Qian Zhang, Yihao Wu, Jingyi Yang, Kevin Zhou, Eric Nigel Ebenezer Anand Manoharan, Tyra Wentz, Leon Su, Alvin Yu, Hong-Yi Wang, Laurakay Bruhn, Israel Steinfeld, Nicolas Gonzalez, Edward Z Song, Yunlin Zhang, Morgan E Hresko, Daniel E Ryan, Nils W Engel, Selene Nunez-Cruz, Carl H June, K Christopher Garcia, Michael C Milone","doi":"10.1016/j.bict.2025.100019","DOIUrl":"10.1016/j.bict.2025.100019","url":null,"abstract":"<p><p>Building on the enhancing effects of the orthogonal interleukin-2 (oIL-2) system for T-cell immunotherapy, we explored a viral vector-free strategy for generating orthogonal chimeric antigen receptor (orthoCAR) T cells. We show that prime editing can generate orthogonal IL-2Rβ (oIL-2Rβ) mutations in T cells with an average efficiency of 72% (range, 54%-89%). The mutations are functional, enrich ex vivo when cultured with oIL-2 and enhance the engraftment, efficacy, and toxicity of CAR T cells in vivo comparable to orthoCAR T cells generated by cotransduction of the oIL-2Rβ and CAR. We further show that the insertion of a CD19-specific CAR with a chicken β-globin promoter into the IL-2 locus (IL-2-CAR19) can be achieved by a CRISPR/CRISPR-associated protein 9 (Cas9)-triggered homology-directed repair with an average efficiency of 46% (range, 30%-65%) in primary T cells. IL-2-CAR19 T cells show a >3-log reduction in IL-2 production consistent with a >96% IL-2 gene disruption. Despite the loss of autocrine IL-2 secretion, IL-2-CAR19 T cells rapidly and potently kill NALM-6 leukemic cells in vitro and in vivo without the need for exogenous IL-2 support. Combining the prime editing of oIL-2Rβ with IL-2-CAR19 T cells yields orthoCAR T cells that exhibit in vitro and in vivo function comparable to lentivirally generated orthoCAR T cells. The prime editing of oIL-2Rβ expands the potential application of the orthogonal IL-2 system to existing T-cell therapies. Moreover, the robust functional activity of IL-2-CAR19 cells highlights the dispensable nature of the IL-2 gene in CAR T cells and its availability for the target insertion of genetic payloads.</p>","PeriodicalId":520924,"journal":{"name":"Blood immunology & cellular therapy.","volume":"1 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13082782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147701869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Donor lymphocyte infusions after HCT are associated with low risk of graft-versus-host disease in pediatric and young adult patients.","authors":"Shruthi Suryaprakash, Yilun Sun, Dinesh Keerthi, Amr Qudeimat, Ali Suliman, Aimee C Talleur, Esther Obeng, Ewelina Mamcarz, Renee Madden, Rebecca Epperly, Senthil V Bhoopalan, Swati Naik, Caitlin C Zebley, M Paulina Velasquez, Paula Arnold, Li Tang, Stephen Gottschalk, Brandon M Triplett, Akshay Sharma","doi":"10.1016/j.bict.2025.100016","DOIUrl":"10.1016/j.bict.2025.100016","url":null,"abstract":"<p><p>Donor lymphocyte infusion (DLI) enhances the graft-versus-leukemia effect and can prevent graft rejection after an allogeneic hematopoietic cell transplant (HCT), but its use is limited by the risk of graft-versus-host disease (GVHD). From 2005 to 2021, 179 patients received 191 HCTs, followed by ≥1 DLIs (n = 626), and 561 patients received 608 HCTs without subsequent DLI. Among DLI recipients, 31.4% and 12.6% developed acute GVHD (aGVHD) and chronic GVHD (cGVHD), respectively, compared with 39% and 18.1%, respectively, of HCT recipients who did not receive DLI (<i>P</i> = .06 for aGVHD, <i>P</i> = .08 for cGVHD). A longer interval between HCT and DLI was associated with a decreased risk of aGVHD. The overall response to DLI for mixed chimerism was 45.2% for HCTs using matched sibling donors, 33.3% for HCTs using matched unrelated donors, and 43.1% for haploidentical HCTs. In our study, the incidence of GVHD among pediatric HCT recipients was similar regardless of whether they received DLI after HCT or not. The risk of GVHD decreased as the interval between HCT and DLI increased, and there was an encouraging response rate for patients receiving DLI for mixed chimerism. Hence, DLI offers a potential therapeutic option for patients with impending graft rejection.</p>","PeriodicalId":520924,"journal":{"name":"Blood immunology & cellular therapy.","volume":"1 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13293487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148335693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}