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Journal articles on the topic 'Non-permissive mismatche'

Author: Grafiati

Published: 9 March 2023

Last updated: 19 July 2025

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1

Chiusolo, Patrizia, Teresa Lamparelli, Giuseppe Sapienza, et al. "The Impact of Aminoacid Substitution at Position 116 Class I HLA, in Unrelated Donor Transplants." Blood 134, Supplement_1 (2019): 4620. http://dx.doi.org/10.1182/blood-2019-130614.

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Background : The role of aminoacid substitution at position 116 of class I HLA antigens, has been the subject of several contributions, suggesting the possibility of permissive or non permissive mismatches. Hypothesis. Permissive mismatched at position AA116, yield outcomes comparable to 10/10 matched grafts and superior to AA116 non permissive mismatches. Patients: We have analyzed 358 unrelated donor transplants (UD) to test this hypothesis. All donors were matched at class II for DRB1 and DQ alleles; 226 were also matched at high resolution for A,B and C alleles; 84 had 1 permissive AA116 m

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2

Shaw, Bronwen E., Katharina Fleischhauer, Mari Malkki, et al. "Permissive HLA-DPB1 Mismatching Compared to a Non-Permissive Mismatching Significantly Improves Overall Survival Following Allogeneic Transplantation In Patients with Both 10/10 and 9/10 Matched Unrelated Donors." Blood 116, no. 21 (2010): 227. http://dx.doi.org/10.1182/blood.v116.21.227.227.

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Abstract Abstract 227 It is well established that the use of a donor matched for 9–10/10 alleles at HLA-A,-B,-C,-DRB1,-DQB1 significantly improves overall survival (OS) after unrelated donor (UD) haematopoietic stem cell transplantation (HSCT). Whilst the matching status for HLA-DPB1 alleles has been shown to influence transplant complications (relapse and graft-versus-host disease (GVHD), its impact on survival has not been well defined. The current unmet need in clinical practice is an approach to stratify selection criteria when a clinician is confronted with the choice between several 10/1

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3

Michallet, Mauricette, Mohamad Sobh, Hélène Labussière-wallet, et al. "Allogeneic Hematopoietic Stem Cell Transplantation from Unrelated Peripheral Blood or Bone Marrow Donors: The Impact of HLA Matching Including HLA-DPB1 Allele in a Multivariable Risk Model." Blood 126, no. 23 (2015): 3213. http://dx.doi.org/10.1182/blood.v126.23.3213.3213.

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Abstract Introduction Allogeneic hematopoietic stem cell transplantation (allo-HSCT) from unrelated donors has been increasingly used worldwide in the last decade in patients with hematological malignancies when HLA-identical sibling donors are unavailable. Identification of the HLA locus matching at the allele level is important in optimizing transplantation outcomes by minimizing non-relapse mortality (NRM) as well as in enhancing the graft-versus-leukemia effect. It has been demonstrated that patients with HSC donors matched on HLA-A, -B, -C, -DRB1, and -DQB1 alleles can have different outc

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4

Arrieta-Bolanos, Esteban, Pietro Crivello, Meilun He, et al. "A Refined Model of HLA-DP Permissiveness Improves Stratification of Acute Graft-Versus-Host Disease Risks after Unrelated Hematopoietic Cell Transplantation: A Retrospective Study from the CIBMTR." Blood 138, Supplement 1 (2021): 2890. http://dx.doi.org/10.1182/blood-2021-146957.

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Abstract Introduction: Permissive HLA-DPB1 mismatches defined by the T-cell epitope (TCE) model are an established selection criterion for unrelated donors in allogeneic hematopoietic cell transplantation (alloHCT) (Dehn et al. Blood 2019). Based on biological evidence, the TCE model has classified HLA-DPB1 alleles into at least three functional groups, one of which (TCE group 3; TCE3) houses a large number of alleles with different structural and functional characteristics. We have recently shown that structurally close HLA-DP allotypes have similar peptide-binding motifs and share a signific

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5

Shike, Hiroko, and Aiwen Zhang. "HLA and Non-HLA Factors for Donor Selection in Hematopoietic Stem Cell Transplantation with Post-Transplant Cyclophosphamide GvHD Prophylaxis." Cells 13, no. 24 (2024): 2067. https://doi.org/10.3390/cells13242067.

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Human leukocyte antigen (HLA) mismatches in stem cell transplantation can be well-tolerated with the use of post-transplant cyclophosphamide (PTCy) for graft-versus-host-disease (GvHD) prophylaxis. Haploidentical (Haplo) and HLA-mismatched unrelated donors become acceptable donors. This review focuses on Haplo and unrelated donor selection in the context of PTCy-transplant for hematological malignancy, in comparison with conventional GvHD prophylaxis. Evaluating patient’s donor-specific antibody (DSA) is critical in donor selection regardless of donor type or the use of PTCy. High DSA levels a

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6

Oran, Betul, Rima M. Saliba, Yudith Carmazzi, et al. "Increased Disease Progression in HLA-a, -B, -C, -DRB1 and -DBP1 Matched Recipients of Unrelated Donor Transplants with Peripheral Blood Is Independent of Risk Groups By Disease Risk Index." Blood 126, no. 23 (2015): 2005. http://dx.doi.org/10.1182/blood.v126.23.2005.2005.

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Abstract The use of unrelated donors matched in all alleles of HLA-A, -B, -C, and -DRB1 loci has been associated with superior outcomes compared with those having 1 or more mismatches. Recent studies showed increased transplant-related mortality (TRM) with the use of HLA-DPB1 mismatched donors supporting the notion that the ideal volunteer unrelated donor should fully match at HLA-A, -B, -C, and -DRB1 and lack -DPB1 mismatches. The issue of the effect of HLA-DPB1 mismatch on the disease progression rate is still controversial and we aimed to investigate the impact of HLA-DPB1 mismatch in the g

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7

Metzing, Maximilian, Pietro Crivello, Thuja Meurer, et al. "HLA-DM Mediates Permissiveness of HLA-DPB1 T Cell Epitope Mismatches in Unrelated HCT." Blood 134, Supplement_1 (2019): 3211. http://dx.doi.org/10.1182/blood-2019-129921.

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Introduction: In 8/8 matched unrelated donor (UD) hematopoietic cell transplantation (HCT), permissive HLA-DPB1 (DP) mismatches within the same functional T Cell Epitope (TCE) group are associated with better outcomes compared to non-permissive mismatches across different TCE groups (Fleischhauer, Blood 2017). This clinical advantage has been shown to be associated with limited in vitro T cell alloreactivity (Meurer, Front Immunol 2019), which in turn is dependent on polymorphic peptide contact amino acids in the DP molecule (Crivello, Biol Blood Marrow Transplant 2015). The HLA class II immun

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8

Ruggeri, Annalisa, Carlheinz Mueller, Liesbeth C. de Wreede, et al. "Association of Donor-Recipient HLA Matching with Outcome of Unrelated Donor Hematopoietic Stem Cell Transplantation: A Study from the Cellular Therapy and Immunobiology Working Party (CTIWP) of the European Society for Blood and Marrow Transplantation (EBMT)." Blood 134, Supplement_1 (2019): 3281. http://dx.doi.org/10.1182/blood-2019-125369.

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Introduction: Optimal HLA matching is associated with clinical outcome of unrelated donor (UD) hematopoietic cell transplantation (HCT)(Pidala, Blood2014, Morishima, Blood2015, Fürst, Blood2013), but a comprehensive analysis addressing this question in European transplant centers has not yet been performed. Within the CTIWP of EBMT, we have addressed this issue in adultsreceiving an UD-HCT from 2000 to 2015. Methods: All consecutive cases of UC-HCT with available 6-loci high resolution (2nd field) HLA-A, -B, -C, -DRB1, -DQB1, -DPB1 typing for both patient and donor and ARD-level matching for a

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9

Smallbone, Portia, Kai Cao, Rima M. Saliba, et al. "HLA-DPB1 Mismatches and the Impact on Unrelated Donor Transplant Outcomes with the Use of Post-Transplant Cyclophosphamide." Blood 144, Supplement 1 (2024): 4937. https://doi.org/10.1182/blood-2024-200238.

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Background Disease progression, graft-versus-host disease (GvHD) and non-relapse mortality are the main causes of failure after allogeneic hematopoietic cell transplantation (HCT). There have been many studies focusing on the biological models of HLA-DPB1 mismatching, namely permissiveness according to T-cell epitope (TCE) groups to determine their association with the risks of non-relapse mortality (NRM) and GvHD/relapse. Most studies were conducted prior to the advent of post-transplant cyclophosphamide (PTCy) as standard GvHD prophylaxis for matched unrelated donor (MUD) transplants. Thus,

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Lee, Yoo Jin, Joon Ho Moon, In Hee Lee, et al. "Killer Cell Immunoglobulin-like Receptor Ligand Matching Determines the Post-Transplant High Risk Groups Among Patients with Permissive HLA Mismatch in Unrelated Donor Hematopoietic Cell Transplantation." Blood 128, no. 22 (2016): 4566. http://dx.doi.org/10.1182/blood.v128.22.4566.4566.

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Abstract Background: Human leukocyte antigen (HLA) matching between donor and recipient is a key part of successful allogeneic hematopoietic cell transplantation (allo-HCT). The HCT from the unrelated donor (UD) with one allele/antigen mismatch (MM) can be as beneficial as HCT from perfectly matched donor. For the remaining patients, the donors with permissive mismatches may be the option. In HLA-mismatched transplantation, the patient and donor can also be mismatched for their killer cell immunoglobulin-like receptor (KIR) ligands that recognize allotypic determinants shared by certain HLA cl

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Brotto, Nágila, ALBERTO CARDOSO MARTINS LIMA, and CARMEM MARIA SALES BONFIM. "MODELS OF HLA-DPB1 PERMISSIVENESS AND UNRELATED DONOR HEMATOPOIETIC CELL TRANSPLANTATION." JOURNAL OF BONE MARROW TRANSPLANTATION AND CELLULAR THERAPY 5, no. 1 (2024): 221. http://dx.doi.org/10.46765/2675-374x.2024v5n1p221.

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In current allo-HCT practice, a fully HLA-matched sibling donor is the best donor associated with improved transplant outcomes. When a matched sibling donor is unavailable, the second best available donor option is a matched unrelated donor (MUD), either HLA 8/8 or HLA 10/10. One notable characteristic in the MUD setting is that HLA-DPB1 mismatches are present in around 80/85% of unrelated donor/recipient pairs. This unique feature has an additional layer of complexity as these HLA-DPB1 incompatibilities may be further divided into permissive and non-permissive mismatches by two biological-dri

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12

Sandhu, Karamjeet S., Ketevan Gendzekhadze, Dongyun Yang, et al. "Prediction of Graft-Versus-Host Disease in Recipients of Single Mismatched Unrelated Hematopoietic Cell Transplantation Donor Using a Highly Multiplexed Proteomic Assay, MHC-Pepseq." Blood 138, Supplement 1 (2021): 1808. http://dx.doi.org/10.1182/blood-2021-153597.

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Abstract Graft-versus-host disease (GVHD) remains a major cause of treatment failure after allogeneic hematopoietic cell transplantation (alloHCT). In HLA-mismatched donor setting, indirect presentation of allogeneic peptides from recipient's mismatched HLA class I or II proteins by donor or recipient antigen presenting cells can be an immunogenic driver of GVHD. However, the potential diversity of such antigens is large, and predicting them in a systematic manner has proven challenging. Using a novel, highly-multiplexed peptide-MHC binding assay (MHC-PepSeq) we sought to 1) identify allogenei

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Beelen, Dietrich W., Pietro Crivello, Andreas Heinold, et al. "The Functional Distance Between Mismatched HLA-DPB1 Increases Risks of Relapse and Mortality after Unrelated Donor Hematopoietic Cell Transplantation for AML, ALL and MDS: A Refinement of the T Cell Epitope Group Algorithm for Permissive Mismatches." Blood 126, no. 23 (2015): 4288. http://dx.doi.org/10.1182/blood.v126.23.4288.4288.

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Abstract Background: We and others have previously shown that non-permissive T cell epitope (TCE) group mismatches at HLA-DPB1 are associated with the risks of mortality after hematopoietic cell transplantation (HCT) from 10/10 HLA-matched unrelated donors (Fleischhauer et al, Lancet Oncol 2012; Pidala et al, Blood 2014). Moreover, we recently reported that TCE groups are reflected by a numerical score assignable to each HLA-DPB1 allele based on the combined median impact of 12 naturally occurring amino acid substitutions (AAS) on allorecognition of HLA-DPB1*09:01 as reference, termed function

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Iwasaki, Makoto, Junya Kanda, Hidenori Tanaka, et al. "Impact of Human Leukocyte Antigen Epitope Matching on Outcomes after Unrelated Bone Marrow Transplantation." Blood 138, Supplement 1 (2021): 3914. http://dx.doi.org/10.1182/blood-2021-145686.

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Abstract Background The immunological effect of human leukocyte antigen (HLA) disparity has not been fully elucidated by the number and locus of HLA antigens or alleles. Several methods to predict epitopes recognized by the immune system have been developed to understand the immunogenicity of amino acid sequences in mismatched HLA pairs. We investigated the association between mismatching of HLA antibody-identified epitopes and hematopoietic stem cell transplantation (HSCT) outcomes. Patients and Methods This was a retrospective cohort study with 9,991 patients who underwent their first HSCT f

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Crocchiolo, Roberto, Elisabetta Zino, Nicoletta Sacchi, et al. "NON-Permissive HLA-DPB1 T CELL Epitope Disparities Correlate with Engraftment and Survival after Unrelated Stem Cell Transplantation." Blood 112, no. 11 (2008): 562. http://dx.doi.org/10.1182/blood.v112.11.562.562.

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Abstract Over 80% of stem cell transplantations (SCT) from unrelated donors (UD) are performed across allelic HLA-DPB1 disparities which have been associated with acute graft-versus-host disease (aGvHD) and, in 10/10 matched pairs, protection from disease relapse, while no significant correlation with overall survival (OS) could be revealed so far. We have previously developed an algorithm for non-permissive HLA-DP disparities involving an immunogenic T cell epitope (TCE) encoded by DPB1*0901, *1001 and *1701 (group 1), and, in a weaker form, by DPB1*0301, *1401 and *4501 (group 2) (Zino et al

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16

Solomon, Scott R., Michael A. Aubrey, Xu Zhang, et al. "Selecting the Best Donor for T Cell-Replete Haploidentical Transplantation: Importance of HLA Disparity, NK Alloreactivity, and Other Clinical Variables." Blood 130, Suppl_1 (2017): 670. http://dx.doi.org/10.1182/blood.v130.suppl_1.670.670.

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Abstract Lack of a matched sibling or unrelated donor can be a significant barrier to allogeneic hematopoietic cell transplantation (HCT). Haploidentical (haplo) donors are readily available for nearly all such patients. However, donor selection criteria to determine the optimal haplo donor are not readily available. In order to determine which donor characteristics are most important in predicting transplant success, we retrospectively analyzed 208 consecutive donor-recipient pairs receiving haplo HCT with post-transplant cyclophosphamide for hematologic malignancy. Donor characteristics were

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Mehta, Rohtesh S., Effie W. Petersdorf, Stephen R. Spellman, and Stephanie J. Lee. "Combined Effect of Unrelated Donor Age and HLA Peptide-Binding Motifs (PBM) Match Status on HCT Outcomes." Blood 142, Supplement 1 (2023): 1045. http://dx.doi.org/10.1182/blood-2023-173887.

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Background: HLA-mismatched unrelated donors (MMUDs) can be either matched or mismatched at protein binding motifs (PBM), while all HLA-matched donors are PBM-matched. A MMUD who is class I PBM-matched in the graft-vs-host (GVH) direction is preferred over a PBM-mismatched donor [ JCO.2023;41(13):2416]. As donor age is also an important prognostic factor, we hypothesized that using a younger donor could compensate for the inferior overall survival (OS) associated with PBM-mismatches. Specifically, we tested if OS after transplantation with HLA-mismatched/PBM-matched/younger donors is similar to

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Tsirigotis, Panagiotis, Ioanna Lazana, Ioannis Konstantellos, et al. "Low Dose Post-Transplant Cyclophosphamide in Combination with Alemtuzumab As Gvhd-Prophylaxis Is Associated with Improved Outcomes and Safe Side Effect Profile in HLA-Mismatched Unrelated Transplantation." Blood 144, Supplement 1 (2024): 2155. https://doi.org/10.1182/blood-2024-210357.

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Introduction Over the last years, there has been increasing interest in the use of posttransplant cyclophosphamide (PTCy) as graft-versus-host disease (GvHD) prophylaxis, given its huge success in the haploidentical setting. PTCy has been increasingly used in patients with HLA-matched related and unrelated donors, with encouraging results in terms of improved TRM and GvHD-free relapse-free survival. However, this comes at the cost of higher risk of side effects (such as hemorrhagic cystitis and viral infections) and delayed hematopoietic reconstitution, along with a potential increased risk of

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Arrieta-Bolaños, Esteban, Maryam Mohamaddokht, Thuja Meurer, et al. "Relative Contribution of Naïve and Memory T Cells to Alloreactivity in Hematopoietic Cell Transplantation." Blood 134, Supplement_1 (2019): 1923. http://dx.doi.org/10.1182/blood-2019-130273.

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Introduction: Graft-versus-host disease (GvHD) is a major impediment to the cure of blood disorders by hematopoietic cell transplantation (HCT). GvHD is mediated by alloreactive T cells recognizing histocompatibility antigen (HAg) mismatches between patient and donor. Naïve T cells are thought to be the main mediators of alloreactive responses since, theoretically, memory T cells would have never been exposed to and selected by alloantigens, except in multiparous women or transfused individuals. Accordingly, clinical trials using naïve T cell-depleted allografts are being conducted with the ai

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Getz, J., N. T. Brotto, R. Ribas Muratori, et al. "Non-permissive HLA-DPB1 mismatches are associated with increased 1-year mortality after unrelated donor hematopoietic cell transplantation for non-malignant disorders." Human Immunology 85 (September 2024): 110871. http://dx.doi.org/10.1016/j.humimm.2024.110871.

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21

Rutten, Caroline E., Simone A. P. van Luxemburg-Heijs, Edith D. van der Meijden, Marieke Griffioen, Roelof Willemze, and J. H. Frederik Falkenburg. "HLA-DPB1 Mismatching Results in the Generation of a Full Repertoire of HLA-DPB1 Specific T Cell Responses Showing Immunogenicity of All HLA-DPB1 Alleles." Blood 112, no. 11 (2008): 3504. http://dx.doi.org/10.1182/blood.v112.11.3504.3504.

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Abstract In unrelated donor hematopoietic stem cell transplantation (URD-SCT) patients are preferably transplanted with stem cells from a fully HLA matched donor, usually defined as identical for HLA-class I, -DR and -DQ. Since HLA-DPB1 is often not taken into consideration in donor selection, 80–90% of URD-SCTs are mismatched for HLA-DPB1. The role of HLA-DPB1 as transplantation antigen has been unclear, since clinical reports on the impact of matching for HLA-DPB1 on transplant outcome showed conflicting results. HLA-DPB1 mismatching has been associated with an increased risk of graft versus

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Solomon, Scott R., Michael T. Aubrey, Xu Zhang, et al. "Optimizing Donor Selection for Haploidentical Transplantation Utilizing the Four-Group T Cell Epitope (TCE-4) Algorithm for Prediction of HLA-DPB1 Non-Permissive Mismatches." Blood 138, Supplement 1 (2021): 420. http://dx.doi.org/10.1182/blood-2021-149289.

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Abstract An HLA-DPB1 non-permissive mismatch (npmm) has been associated with higher risks of acute graft-versus-host disease and non-relapse mortality after matched unrelated donor transplantation (MUDT) and thus avoiding HLA-DPB1 npmm is important in unrelated donor selection. In contrast, HLA-DPB1 npmm by the 3-group T cell epitope algorithm (TCE-3) has been shown to be protective in the context of haploidentical donor transplantation (HIDT) using post-transplant cyclophosphamide (PTCy) (Solomon et al. BBMT 2018). Additional HLA-DPB1 "permissiveness" models, also based on cross-reactive patt

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Solh, Melhem M., Asad Bashey, Michael T. Aubrey, et al. "The Degree of HLA-DPB1 Mismatch Predicted By Evolutionary Divergence Scoring Informs the Risk of Chronic Graft-Versus-Host Disease after Haploidentical Transplantation with Post-Transplant Cyclophosphamide." Blood 144, Supplement 1 (2024): 4913. https://doi.org/10.1182/blood-2024-210329.

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In the context of haploidentical donor transplantation (HIDT) utilizing post-transplant cyclophosphamide (PTCY), our group has previously demonstrated that mismatch at HLA-DPB1 predicts a higher incidence of chronic GVHD, regardless of permissiveness by the TCE algorithm or directionality of the mismatch. HLA Evolutionary Divergence (HED) can predict the quantify of divergence between two alleles of the same HLA locus. The divergent allele advantage hypothesis proposes that diversity between HLA alleles of the same locus will increase the capacity of peptide antigen presentation, resulting in

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Morishima, Yasuo, Takakazu Kawase, Keitaro Matsuo, et al. "Identification of Non-Permissive HLA Allele Mismatch Combinations and Amino Acid Substitution Responsible for Acute Graft-Versus-Host Disease in Unrelated Allogeneic Bone Marrow Transplantation." Blood 108, no. 11 (2006): 170. http://dx.doi.org/10.1182/blood.v108.11.170.170.

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Abstract Background: In the allogenic hematopoietic stem cell transplantation from unrelated donors (UR-HSCT), an effect of HLA locus mismatch in allele level on clinical outcome has been clarified. However, the effect of each HLA allele mismatch combinations is little known, and its molecular mechanism to induce acute graft versus host disease (aGVHD) remained to be elucidated. Methods: Consecutive 4866 patients transplanted with T cell replete marrow from a serologically HLA-A, -B and -DR antigen-matched donor through Japan Marrow Donor Program were registered in this cohort study. All HLA-A

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Pingel, Julia, Camila J. Hernandez Frederick, Tao Wang, et al. "Evaluation of the Impact of Non-Inherited Maternal Antigens on the Outcome of HLA Mismatched Unrelated Donor Hematopoietic Stem Cell Transplantation for Hematological Malignancies on Behalf of the ALWP of the EBMT and the CIBMTR." Blood 126, no. 23 (2015): 3226. http://dx.doi.org/10.1182/blood.v126.23.3226.3226.

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Abstract Allogeneic hematopoietic stem cell transplantation (HSCT) offers a potential cure for a variety of hematological malignancies. Patients without an HLA matched sibling donor can turn to unrelated donor registries to identify a suitably HLA matched donor. In the case where a fully HLA-A, -B, -C, -DRB1 and -DQB1 (10/10) matched donor is unavailable, there are often multiple 9/10 matched donors to select from. However, the prioritization and identification of permissive HLA mismatches in the 9/10 matched setting have proven elusive. Fetal exposure to non-inherited maternal antigens (NIMA)

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Kittisares, Kulvara, Pietro Crivello, Thorben Walther, et al. "Memory CD4+ T Cells Recognize Divergent HLA-DP Immunopeptidomes and Contribute to Leukemia Control after Allogeneic HCT." Blood 144, Supplement 1 (2024): 901. https://doi.org/10.1182/blood-2024-210787.

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While naïve T cells are considered the main mediators of alloreactivity after hematopoietic cell transplantation (HCT), the role of memory T cells in these allo-immune responses and their clinical consequences is more debated. Differences between naïve and memory subsets are at the basis of clinical trials using naïve cell-depleted grafts in allogeneic HCT (Bleakley, J Clin Invest 2015 and JCO 2020). In unrelated HCT, patient and donor HLA-DP allotypes present immunopeptidomes with different degrees of divergence regulated by the peptide editor HLA-DM, which determine the strength and diversit

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Zino, Elisabetta, Luca Vago, Simona Di Terlizzi, et al. "Epitope-Specific Typing (EST) for HLA-DPB1 Matching: Proof of Principle for an Innovative Approach to Unrelated Hematopoietic Stem Cell Donor Selection." Blood 108, no. 11 (2006): 3130. http://dx.doi.org/10.1182/blood.v108.11.3130.3130.

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Abstract Background. Conventional matching of patients and their unrelated donor (UD) hematopoietic stem cells (HSC) by 4-digit molecular HLA typing is associated with lengthy donor searches and elevated social costs. 80% of UD transplants are performed across DPB1 mismatches which, if involving disparity in host versus graft (HvG) direction for an immunogenic T cell epitope, have been shown to be associated with poor clinical outcome of transplantation for hematopoietic malignancies and beta-thalassemia. In this study we have developed an innovative approach of DPB1 epitope- rather than allel

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Fuchs, Ephraim J., Shannon R. McCurdy, Scott R. Solomon, et al. "Improving Donor Selection for Haploidentical Stem Cell Transplantation with Post-Transplant Cyclophosphamide through Selective HLA-Mis/Matching." Blood 136, Supplement 1 (2020): 24–26. http://dx.doi.org/10.1182/blood-2020-140433.

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Background HLA-haploidentical (haplo) blood or marrow transplantation (BMT) with post-transplantation cyclophosphamide (PTCy) is widely used, but few factors that inform donor selection have been identified. Based on prior observations for HLA-B leader (EW Petersdorf et al. Lancet Haematol 2020), HLA-DRB1 (YL Kasamon et al. BBMT 2010), and HLA-DPB1 (SR Solomon et al. BBMT 2018), we hypothesized that mismatching at individual HLA loci may influence BMT outcomes, but single and additive HLA gene effects have not been evaluated systematically in the context of haploBMT with PTCy. Methods The Cent

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Lorentino, Francesca, Nicoletta Sacchi, Elena Oldani, et al. "Permissive HLA-DPB1 Mismatch and Survival after Unrelated Donor Allogeneic Stem Cell Transplantation for Hematological Malignancies: A Comparative Analysis of Different Immunogenetic Models on 422 Patients from GITMO and IBMDR." Blood 132, Supplement 1 (2018): 482. http://dx.doi.org/10.1182/blood-2018-99-115216.

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Abstract Introduction: Hematopoietic Stem Cell Transplantation (HSCT) from unrelated donors (UD) is a curative therapy for many hematologic malignancies. HLA matching plays a major role in determining HSCT outcome but the relative role of incompatibilities at the different HLA loci is still debated. In particular, over 80% of UD-HSCT are performed across HLA-DPB1 mismatches (mm): a number of previous studies have devised immunogenetic models to elucidate the impact of HLA-DPB1 mm on HSCT outcome, but a comparative analysis of these models in a recent and well-characterized cohort is lacking. M

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Ducreux, Stephanie, Valérie Dubois, Pascal Loiseau, et al. "Association Between Multiple Mismatches at the HLA-DPB1 and DRB3/4/5 Genes and Adverse Outcomes in HLA-a, -B, -C, -DRB1 and -DQB1 Identical Hematopoietic Stem Cell Transplantation: A Study on Behalf of the Francophone Society of Stem Cell Transplantation and Cellular Therapy (SFGM-TC) and the Francophone Society for Histocompatibility and Immunogenetics (SFHI)." Blood 128, no. 22 (2016): 4660. http://dx.doi.org/10.1182/blood.v128.22.4660.4660.

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Abstract Background: Matching for all alleles of the HLA-A, -B, -C, and -DRB1 loci (8/8 match) is associated with the highest overall survival (OS) rates after unrelated donor (URD) hematopoietic stem cell transplantation (HSCT). In Europe, patients (pts) are also matched at the HLA-DQB1 loci (10/10 match) with no overall evidence of improved OS. HLA-DPB1 mismatching has been associated with a higher risk of acute graft-versus-host disease (aGvHD) and a decreased risk of relapse. A detrimental role of additional HLA-DQB1, HLA-DPB1 and HLA-DRB3/4/5 mismatches (MM) has been recently identified o

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Solomon, Scott R., Michael T. Aubrey, Lizamarie Bachier-Rodriguez, et al. "Impact of an HLA-DPB1 Non-Permissive Mismatch By the Revised T Cell Epitope (TCE)-Core Algorithm on Survival Following Haploidentical Donor Transplantation (HIDT) with Post-Transplant Cyclophosphamide (PTCy)." Blood 142, Supplement 1 (2023): 2240. http://dx.doi.org/10.1182/blood-2023-182499.

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The presence of an HLA-DPB1 non-permissive mismatch (NPMM) by the TCE-3 model has been associated with improved survival following HIDT utilizing post-transplant cyclophosphamide (PTCy). A revised model (TCE-core) which further separates TCE “group 3” alleles into “core”(C) and “non-core” (NC) alleles has been developed (Arrietta-Bolanos et al. Blood 2022). In this new model, a formerly permissive mismatch (PMM) resulting from “group 3” alleles in both donor and recipient are now considered a C-NPMM if one or more of those alleles is NC (see figure), and the total number of NPMMs by the TCE-co

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Fleischhauer, K., K. W. Ahn, H. L. Wang, et al. "Directionality of non-permissive HLA-DPB1 T-cell epitope group mismatches does not improve clinical risk stratification in 8/8 matched unrelated donor hematopoietic cell transplantation." Bone Marrow Transplantation 52, no. 9 (2017): 1280–87. http://dx.doi.org/10.1038/bmt.2017.96.

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Tanner, Matthew, Aaron Boothby, Danny Youngs, et al. "Donor-Specific Antibody Mean Fluorescence Intensity Threshold Predicts Platelet Transfusion Response in HLA-Alloimmunized Patients." Blood 142, Supplement 1 (2023): 701. http://dx.doi.org/10.1182/blood-2023-185054.

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Introduction:Patients with platelet transfusion refractoriness (PTR) due to HLA-alloimmunization respond to HLA-matched platelets. However, 4/4 HLA-matched platelets or platelets without donor-recipient antigenic mismatches are rarely available. Further, in severe HLA-alloimmunization, it is difficult to find donor products which do not contain antigens to which the recipient has developed antibodies ( i.e. antibody specificity prediction, ASP method). Hence, studies have evaluated platelet transfusion responsiveness in the presence of ≥1 donor specific antibodies (DSAs) to widen donor pools,

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Bribiesca Rodriguez, Josefine, Aaron Boothby, Matthew Tanner, et al. "Impact of Non-Immune Factors on Platelet Transfusion Responses in an Allo-Immunized Cohort." Blood 142, Supplement 1 (2023): 4040. http://dx.doi.org/10.1182/blood-2023-182139.

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Background: Patients with hematologic malignancies and/or hematopoietic stem cell transplantation (HSCT) recipients often require platelet transfusion support for extended periods. This can result in platelet transfusion refractoriness (PTR) from HLA alloimmunization in up to 30% of individuals. These medically complex patients may also have splenomegaly, fevers and other factors which contribute to PTR. Consequently, they may demonstrate variability in immediate platelet recovery (at 0-2 hours post-transfusion), and in subsequent platelet consumption (at 18-24 hours) despite receiving HLA-sel

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Gaziev, Javid, Antonella Isgro, Katia Paciaroni, et al. "Outcomes of Unrelated Bone Marrow Transplantation in Patients with Thalassemia." Blood 132, Supplement 1 (2018): 5777. http://dx.doi.org/10.1182/blood-2018-99-109764.

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Abstract Introduction. Bone marrow transplantation from an HLA-matched related or unrelated donor remains the only curative treatment for patients with thalassemia. Although one third of patients with thalassemia can find a matched unrelated donor (MUD) few patients were treated by MUD transplantation. Early experience with the use of MUD transplant in class 3 patients with thalassemia resulted in high rates of graft rejection and transplant-related mortality with thalassemia-free (TFS) survival of 53% (La Nasa G et al. Blood 2002). Significant improvements in MUD transplantation in recent yea

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Bárcena, A., A. H. Galy, J. Punnonen, et al. "Lymphoid and myeloid differentiation of fetal liver CD34+lineage- cells in human thymic organ culture." Journal of Experimental Medicine 180, no. 1 (1994): 123–32. http://dx.doi.org/10.1084/jem.180.1.123.

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In this article, we report that the human fetal thymus contains CD34bright cells (&lt; 0.01% of total thymocytes) with a phenotype that resembles that of multipotent hematopoietic progenitors in the fetal bone marrow. CD34bright thymocytes were CD33-/dull and were negative for CD38, CD2, and CD5 as well as for the lineage markers CD3, CD4, and CD8 (T cells), CD19 and CD20 (B cells), CD56 (NK cells), glycophorin (erythrocytes), and CD14 (monocytes). In addition, total CD34+ lineage negative (lin-) thymocytes contained a low number of primitive myeloid progenitor cells, thus suggesting that

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Saeed, Anwaar, Josep Tabernero, Guan Wang, Xia Ma, Robina Smith, and J. Randolph Hecht. "STELLAR-303: A randomized phase 3 study of zanzalintinib (XL092) plus atezolizumab versus regorafenib in previously treated metastatic colorectal cancer." Journal of Clinical Oncology 42, no. 16_suppl (2024): TPS3634. http://dx.doi.org/10.1200/jco.2024.42.16_suppl.tps3634.

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TPS3634 Background: Metastatic colorectal cancer (mCRC) has seen increased rates in overall survival (OS) as novel targeted agents have become available. Unfortunately, the median OS is still less than 2 years, and the 5-year survival rate is only about 16%. This underscores an unmet need in this population that necessitates finding therapeutic options to enhance treatment outcomes. As monotherapy, immune checkpoint inhibitors (ICIs) have shown limited efficacy in non–microsatellite instability-high (non–MSI-H) mCRC, which represents a majority of mCRC cases. However, addition of tyrosine kina

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Abrams, Thomas Adam, Syed Mohammad Ali Kazmi, Ira Seth Winer, et al. "A phase 1b multitumor cohort study of cabozantinib plus atezolizumab in advanced solid tumors (COSMIC-021): Results of the colorectal cancer cohort." Journal of Clinical Oncology 40, no. 4_suppl (2022): 121. http://dx.doi.org/10.1200/jco.2022.40.4_suppl.121.

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121 Background: Cabozantinib, a multiple receptor tyrosine kinase inhibitor, promotes an immune-permissive environment which may enhance the activity of immune checkpoint inhibitors. COSMIC-021 (NCT03170960) is evaluating the combination of cabozantinib with atezolizumab, an anti-PD-L1 inhibitor, in patients with advanced solid tumors. Outcomes in patients (pts) with metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine-containing therapy are presented. Methods: Pts with mCRC and an ECOG PS of 0–1 who progressed during or following systemic chemotherapy including fluorop

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Saeed, Anwaar, Josep Tabernero, Guan Wang, Xia Ma, Robina Smith, and J. Randolph Hecht. "Zanzalintinib (XL092) plus atezolizumab versus regorafenib in previously treated MSS/MSI-low metastatic colorectal cancer (mCRC): The randomized phase 3 STELLAR-303 study." Journal of Clinical Oncology 42, no. 3_suppl (2024): TPS229. http://dx.doi.org/10.1200/jco.2024.42.3_suppl.tps229.

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TPS229 Background: Patients with microsatellite stable/microsatellite instability-low (MSS/MSI-low) mCRC account for ~95% of mCRC cases, and there is a significant unmet need in patients with treatment-refractory MSS/MSI-low mCRC. Although immune checkpoint inhibitors (ICIs) have shown limited activity in this patient population, the addition of tyrosine kinase inhibitors (TKIs) may increase sensitivity to ICIs by promoting an immune-permissive tumor microenvironment. Furthermore, TKI-ICI combinations have demonstrated encouraging clinical activity in patients with mCRC, particularly in subgro

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Lindner, Sarah, Tobias Berg, Christian Seidel, et al. "Impact of KIR/HLA Incompatibilities after Posttransplant Cyclophosphamide Based T Cell-Replete Haploidentical Hematopoietic Stem Cell Transplantation." Blood 134, Supplement_1 (2019): 3340. http://dx.doi.org/10.1182/blood-2019-125243.

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Introduction: Posttransplantation cyclophosphamide (PTCy) based T cell-replete haploidentical (haplo) hematopoietic stem cell transplantation (HSCT) is a valid option for patients with indication for allogeneic HSCT without a human leucocyte antigen (HLA) matched donor. However, selection criteria to determine the optimal among several available haplo donors are still a matter of debate. Especially, the impact of killer cell immunoglobulin-like receptor (KIR)/human leukocyte antigen (HLA) incompatibilities (inc) in the setting of PTCy T cell-replete haplo HSCT is unclear. PTCy has been reporte

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Luft, Thomas, Katharina Schmidt, Karl-Heinz Kellner, et al. "ATG and Statins Reduce Incidence of Severe Chronic Gvhd By Distinct Mechanisms Involving CXCL9 and Kynurenine Catabolism." Blood 126, no. 23 (2015): 856. http://dx.doi.org/10.1182/blood.v126.23.856.856.

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Abstract Introduction: Severe chronic graft versus host disease (cGVHD) causes debilitating morbidity due to fibrotic and inflammatory changes in connective tissues mainly of skin, lungs, eyes and the gastrointestinal tract. In contrast, mild cGVHD is strongly associated with better overall survival due to lower relapse rates, so that permissive immunosuppressive drug management is actively pursued by many clinicians. Although alloreactive T lymphocytes are clearly involved in the induction of both grades of cGVHD, it is unpredictable which patients are prone to develop severe rather than mild

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Cohen, Sandra, Myriam Labopin, Nadia M. Bambace, et al. "UM171 Expanded Cord Blood Transplantation Outcomes Compare Favorably to All Different Stem Cell Sources: An EBMT Registry Case-Control Analysis." Blood 142, Supplement 1 (2023): 4977. http://dx.doi.org/10.1182/blood-2023-173727.

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Background: Cord blood (CB) transplantation (CBT) has several advantages compared with other graft sources, such as permissive human leucocyte antigen (HLA) mismatches, and low risk of chronic graft-versus-host disease (GVHD) and relapse. However, CBT has fallen into disfavor because of its high risk of non-relapse mortality (NRM) and prolonged hospitalization due to its low cell dose. Furthermore, the need for the rare large cord bloods (CBs) leads to selection of poorly HLA-matched CBs, known to further increase NRM. UM171 is a small molecule that expands hematopoietic stem cells. A phase I-

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Shaw, Bronwen E., Brent R. Logan, Stephen R. Spellman, et al. "Analysis of 10,462 8/8 HLA- Matched Unrelated Donor Transplants Could Not Identify a Donor Selection Score, As Younger Age Is the Only Significant Donor Characteristic Associated with Survival." Blood 130, Suppl_1 (2017): 848. http://dx.doi.org/10.1182/blood.v130.suppl_1.848.848.

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Abstract Background. There is no hierarchical algorithm that weights the characteristics of individual donors against each other in a quantitative manner to facilitate donor selection when multiple potential equally HLA-matched unrelated donors (URD) are available. Donor factors, such as age, sex, CMV status, ABO type, and matching of secondary HLA loci (DQB1, DPB1), have been associated with recipient survival in URD hematopoietic cell transplantation (HCT) although the impact of specific factors has varied among studies. The goal of this study was to develop and validate a donor selection sc

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Mytilineos, Daphne, Chrysanthi Tsamadou, Christine Neuchel, et al. "The Human Leukocyte Antigen-DPB1 Degree of Compatibility Is Determined by Its Expression Level and Mismatch Permissiveness: A German Multicenter Analysis." Frontiers in Immunology 11 (January 25, 2021). http://dx.doi.org/10.3389/fimmu.2020.614976.

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T-cell epitope matching according to the TCE3 algorithm classifies HLA-DPB1 mismatches in permissive and non-permissive. This classification has been shown to be predictive for mortality and acute GvHD (aGvHD) events in large international cohorts. We retrospectively genotyped HLA-DPB1 in 3523 patients transplanted in Germany between 2000 and 2014 and in their unrelated donors using an Illumina amplicon-NGS based assay. Aim of the study was to evaluate DP-compatibility beyond the established TCE3 algorithm by assessing the combined effect of several DP-mismatch parameters on post-transplant ou

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Mehta, Rohtesh S., Effie W. Petersdorf, Tao Wang, Stephen R. Spellman, and Stephanie J. Lee. "Interplay between donor age and HLA-DP matching in 10/10 HLA-matched unrelated donor HCT." Blood Advances, July 15, 2024. http://dx.doi.org/10.1182/bloodadvances.2024013677.

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In 10/10 HLA-matched unrelated donor (MUD) hematopoietic cell transplantation (HCT) with calcineurin-inhibitor (CNI)-based prophylaxis, T-cell epitope DP-matched and permissive mismatched donors are associated with similar overall survival (OS) while donors with non-permissive mismatches should be avoided. Younger unrelated donors are also favored over older donors. We explored outcomes associated with different combinations of DP-matching and donor age (dichotomized at 35 years) to further guide donor selection. Using a Center for International Blood and Marrow Transplant Research dataset, we

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Liu, Shuang, Tengteng Zhang, Xiaojin Wu, et al. "HLA‐DPB1 and DPA1 ~ DPB1 linkage mismatch affects the survival of recipients receiving HLA‐14/14 matched unrelated donor HSCT." HLA 103, no. 6 (2024). http://dx.doi.org/10.1111/tan.15542.

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To analyse the effect of HLA‐DPA1 and HLA‐DPB1 allelic mismatches on the outcomes of unrelated donor haematopoietic stem cell transplantation (URD‐HSCT), we collected 258 recipients with haematological disease who underwent HLA‐10/10 matched URD‐HSCT. HLA‐A, ‐B, ‐C, ‐DRB1, ‐DQB1, ‐DRB3/4/5, ‐DQA1, ‐DPA1 and ‐DPB1 typing was performed for the donors and recipients using next‐generation sequencing (NGS) technology. After excluding 8 cases with DQA1 or DRB3/4/5 mismatches, we included 250 cases with HLA‐14/14 matching for further analysis. Our results showed that the proportion of matched DPA1 an

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Arrieta-Bolaños, Esteban, Pietro Crivello, Meilun He, et al. "A core group of structurally similar HLA-DPB1 alleles drives permissiveness after hematopoietic cell transplantation." Blood, May 24, 2022. http://dx.doi.org/10.1182/blood.2022015708.

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Clinically tolerable, permissive HLA-DPB1 mismatches defined by the T-cell epitope (TCE) model improve the selection of unrelated donors in allogeneic hematopoietic cell transplantation (HCT). Mechanistically, overlapping immunopeptidomes in structurally close HLA-DP allotypes with similar peptide-binding motifs are fundamental for permissiveness in vitro, but their relevance in vivo is still unknown. Here, we hypothesized that a similarity measure reflecting the peptide-binding region of HLA-DPB1 alleles could constitute a proxy for immunopeptidome overlap and hence predict permissive mismatc

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Senev, Aleksandar, Anat R. Tambur, Vasilis Kosmoliaptsis, et al. "HLA molecular mismatches and induced donor-specific tolerance in combined living donor kidney and hematopoietic stem cell transplantation." Frontiers in Immunology 15 (March 27, 2024). http://dx.doi.org/10.3389/fimmu.2024.1377535.

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IntroductionWe investigated the potential role of HLA molecular mismatches (MM) in achieving stable chimerism, allowing for donor-specific tolerance in patients undergoing combined living donor kidney and hematopoietic stem cell transplantation (HSCT).MethodsAll patients with available DNA samples (N=32) who participated in a phase 2 clinical trial (NCT00498160) where they received an HLA mismatched co-transplantation of living donor kidney and facilitating cell-enriched HSCT were included in this study. High-resolution HLA genotyping data were used to calculate HLA amino acid mismatches (AAMM

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Iwasaki, Makoto, Junya Kanda, Hidenori Tanaka, et al. "Impact of HLA Epitope Matching on Outcomes After Unrelated Bone Marrow Transplantation." Frontiers in Immunology 13 (March 3, 2022). http://dx.doi.org/10.3389/fimmu.2022.811733.

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The significance of antibody-identified epitopes stimulating humoral alloimmunity is not well understood in the identification of non-permissive human leukocyte antigen (HLA) mismatching patterns in hematopoietic stem cell transplantation (HSCT). This was a retrospective study in a cohort of 9,991 patients who underwent their first HSCT for hematologic malignancies from unrelated bone marrow donors in the Transplant Registry Unified Management Program (TRUMP). HLA eplet mismatches (EMM) were quantified using HLAMatchmaker (HLAMM). The median age of patients was 48 years (range, 16 to 77). The

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Meurer, Thuja, Pietro Crivello, Maximilian Frederik Metzing, et al. "Permissive HLA-DPB1 mismatches in HCT depend on immunopeptidome divergence and editing by HLA-DM." Blood, September 6, 2020. http://dx.doi.org/10.1182/blood.2020008464.

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In hematopoietic cell transplantation (HCT), permissive HLA-DPB1 mismatches between patients and their unrelated donors (UD) are associated with improved outcomes compared to non-permissive mismatches, but the underlying mechanism is incompletely understood. Here we used mass spectrometry, T-cell receptor-beta (TCRb) deep sequencing, and cellular in vitro models of alloreactivity to interrogate the HLA-DP immunopeptidome and its role in alloreactive T cell responses. We find that permissive HLA-DPB1 mismatches display significantly higher peptide repertoire overlaps compared to their non-permi

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