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BACKGROUND: Cord blood transplantation (CBT) is an attractive therapeutic option for patients with hematological malignancies. CBT tolerates HLA mismatches between donors and recipients, but which HLA mismatches generate graft-versus-tumor (GVT) effects is unknown. OBJECTIVE: Given that HLA molecules contain epitopes comprising polymorphic amino acids that determine their immunogenicity, we investigated associations between epitope-level HLA mismatches and relapse following single-unit CBT...

BACKGROUND: An increased incidence of subsequent solid cancers (SSCs) has been reported in long-term survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT), and SSC is associated with inferior mortality and morbidity. Previous studies showed that the incidence of SSC is significantly higher in those who underwent allo-HSCT from HLA-mismatched donors, suggesting that persistent alloimmunity may predispose patients to SSCs. It was recently reported that, in a cohort of patients who received allo-HSCT from an unrelated donor matched at HLA-A, -B, -C, -DRB1/3/4/5, and -DQB1 loci, HLA-DPB1 alloimmunity determined by high mismatched eplets (MEs) and Predicted Indirectly Recognizable HLA Epitopes (PIRCHE) score (PS), was associated with relapse protection and increased risk of acute graft-versus-host disease (GVHD)...

PURPOSE: Immunopeptidome divergence between mismatched HLA-DP is a determinant of T-cell alloreactivity and clinical tolerability after fully HLA-A, -B, -C, -DRB1, -DQB1 matched unrelated donor hematopoietic cell transplantation (UD-HCT). Here, we tested this concept in HLA-A, -B, and -C disparities after single class I HLA-mismatched UD-HCT. PATIENTS AND METHODS: We studied 2,391 single class I HLA-mismatched and 14,426 fully HLA-matched UD-HCT performed between 2008 and 2018 for acute leukemia or myelodysplastic syndromes...

Acute GVHD is a potentially severe complication of hematopoietic stem cell transplantation, responsible for morbidity and mortality that can affect the prognosis after transplantation. Within the framework of the 12th workshop of practice harmonization of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC), diagnostic modalities of acute GVHD are updated. The conventional prevention (depending on donor, conditioning, and stem cell source) and treatment schemes (depending on affected organ and intensity) of aGVHD are clarified, and new therapeutic options are discussed...

Regions of Arctic Zone and Far North of Russia have a weak social infrastructure, including regional segments of the state healthcare system. The study of citizens satisfaction with the healthcare system is one of the leading methods for assessing its effectiveness. Citizens satisfaction may be distorted by their health literacy (HL). Half of the 'healthy' citizens (51.1%) had an excellent or sufficient level of general GVH; 2/3 of the patients of medical organizations (70.4%) had an insufficient or problematic level of general HL...

The detection of clonal hematopoiesis (CH) in patients with hematologic neoplasms who are undergoing a cellular therapy is common. The most frequently used cellular therapy procedures include autologous and allogeneic hematopoietic stem cell transplantation (HSCT) and, more recently, chimeric antigen receptor (CAR) T‑cell therapy. All three procedures differ fundamentally in terms of harvesting and manufacturing aspects as well as usage of the respective cell product. Therefore, the importance of CH in relation to the respective treatment method must be evaluated and assessed differently...

Allogeneic hematopoietic cell transplantation (allo-HCT) is an effective immunotherapy against hematopoietic malignancies. The infused donor lymphocytes attack malignant cells and normal tissues, termed a graft-verse-leukemia (GVL) effect and graft-verse-host (GVH) response or disease (GVHD), respectively. Although engineering techniques toward donor graft selection have made HCT more specific and effective, primary tumor relapse and GVHD are still major concerns post allo-HCT. High-dose systemic steroids remain to be the first line of GVHD treatment, which may lead to steroid-refractory GVHD with a dismal outcome...

INTRODUCTION: Graft-versus-host disease (GvHD) is a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is highly influenced by the degree of HLA matching between recipient and donor. The HLA-class Ib molecule HLA-G has been shown to promote tolerogenicity through its interaction with inhibitory receptors found on several immunocompetent cells. We hypothesized that in an allo-HSCT setting, HLA-G mismatches may negatively impact the HLA-G mediated tolerogenicity either due to inefficient interaction with the inhibitory receptors of the transplanted immune cells or due to direct allorecognition of mismatched HLA-G on host cells by the immune cells of the donor...

Ruxolitinib, used in children with steroid-refractory acute graft-versus-host (GVH) disease, is currently commercially available only as a tablet adult dosage. For the paediatric population, an oral liquid would be an adapted dosage formulation. The aim of this study was to develop ruxolitinib compounded oral suspensions at 2 mg/mL by using commercial tablets in available aqueous vehicle (Inorpha) and to measure its stability at both room temperature and under refrigeration. Chemical stability of suspensions containing ruxolitinib was evaluated for 60 days based on pH, degradation, and drug content...

Graft-versus-host disease (GVHD) following liver transplantation is induced by the graft-versus-host (GVH) T cell that is transferred with the liver graft, but the dynamics remain poorly investigated in clinical liver transplantation GVHD. Here, we report that in two liver transplantation recipients who developed GVHD, both of whom showed donor T cell macrochimerism in the blood before clinical GVHD onset. Longitudinal tracking of GVH T cell clones in one of these recipients revealed that GVH T cell clonal expansion occurred before disease onset, and the dominant GVH T cells might also derive from non-hepatic tissue-resident memory T cells in the liver-graft...

BACKGROUND: Currently, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered to be indicated for children and adolescents with high-risk or relapsed T-cell acute lymphoblastic leukemia (T-ALL); however, the outcomes are unsatisfactory. Killer cell immunoglobulin-like receptors (KIRs) are the main receptors on natural killer (NK) cells that play an important role in the graft-versus-leukemia effect after allo-HSCT. In allo-HSCT, when the recipient lacks a donor KIR-ligand (KIR-ligand mismatch in the graft-versus-host [GVH] direction), donor NK cells will be activated against recipient cells...

BACKGROUND: Natural killer cell alloreactivity is determined by killer cell immunoglobulin-like receptor (KIR) ligands in donor and recipient pairs. A small, single institution study suggested that the risk of primary graft failure (PGF) following cord blood hematopoietic cell transplantation (CBT) can be predicted by host-versus-graft (HvG) directed natural killer cell alloreactivity. In the haploidentical transplant (Haplo HCT) cohort, graft failures were observed only in graft-versus-host (GvH) KIR ligand mismatched pairs...

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)...

A survey of recently discovered vitiviruses was performed on 113 Croatian autochthonous grapevine cultivars from the national collection "Jazbina" using one-step RT-PCR. The presence of grapevine virus H (GVH) was confirmed in nine (7.9%) cultivars and grapevine virus G in eight (7.1%), while the presence of grapevine viruses I and J were not detected. GVH was transmitted by the vine mealybug ( Planococcus ficus ) from a source plant to grapevine seedlings with a 10.5% transmission rate using a combination of 10 first and second instars per plant with 48 and 72 h of acquisition and inoculation access period, respectively...

The number of haploidentical hematopoietic stem cell transplantations (haplo-HSCT) performed has increased substantially in recent years. Previous single-center studies using in silico algorithms to quantitively measure HLA disparity have shown an association of the number of HLA molecular mismatches with relapse protection and/or increased risk of acute graft-versus-host disease (GVHD) in haplo-HSCT. However, inconsistent results from small studies have made it difficult to understand the full clinical impact of molecular mismatch in haplo-HSCT...

Graft-versus-host disease (GVHD) is a critical complication after allogeneic haematopoietic stem cell transplantation induced by genetic differences in donor-recipient pairs. Rigorous HLA matching has reduced GVHD, but severe GVHD still occurs. Minor histocompatibility antigens (mHAs) are another source of GVHD inducers. We designed a multi-mHA panel with 35 valid mHA loci and retrospectively analyzed 391 donor-recipient pairs with the anticipation of implementing mHA typing into clinical practice to optimize donor selection...

Hematopoietic cell (HC) transplantation (HCT) is the last resort to cure hematopoietic malignancies that are refractory to standard therapies. Hematoablative treatment aims at wiping out tumor cells as completely as possible to avoid leukemia/lymphoma relapse. This treatment inevitably co-depletes cells of hematopoietic cell lineages, including differentiated cells that constitute the immune system. HCT reconstitutes hematopoiesis and thus, eventually, also antiviral effector cells. In cases of an unrelated donor, that is, in allogeneic HCT, HLA-matching is performed to minimize the risk of graft-versus-host reaction and disease (GvHR/D), but a mismatch in minor histocompatibility antigens (minor HAg) is unavoidable...

HLA-DPB1 mismatches between donor and recipient are commonly seen in allogeneic hematopoietic stem cell transplantation (HSCT) from an unrelated donor. HLA-DPB1 mismatch, conventionally determined by the similarity of the T-cell epitope (TCE), is associated with an increased risk of acute graft-versus-host disease (aGVHD) and a decreased risk of disease relapse. We investigated the clinical impact of HLA-DPB1 molecular mismatch quantified by mismatched eplets (ME) and Predicted Indirectly Recognizable HLA Epitopes score (PS) in a cohort of 1,514 patients receiving HSCT from unrelated donors matched at HLA-A, -B, -C, -DRB1/3/4/5, and -DQB1 loci...

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematological malignancies. This beneficial effect is derived mainly from graft-versus-leukemia (GVL) effects mediated by alloreactive T cells. However, these alloreactive T cells can also induce graft-versus-host disease (GVHD), a life-threatening complication after allo-HSCT. Significant progress has been made in the dissociation of GVL effects from GVHD by modulating alloreactive T cell immunity. However, many factors may influence alloreactive T cell responses in the host undergoing allo-HSCT, including the interaction of alloreactive T cells with both donor and recipient hematopoietic cells and host non-hematopoietic tissues, cytokines, chemokines and inflammatory mediators...

Signal-regulatory protein α (SIRPα), a polymorphic inhibitory membrane-bound receptor, and its ligand CD47 have recently been implicated in the modulation of innate immune allorecognition in murine models. Here, we investigate the potential impact of SIRPα donor-recipient mismatches on graft outcomes in human kidney transplantation. To eliminate the specific role of HLA-matching in alloresponse, we genotyped the two most common variants of SIRPα in a cohort of 55 HLA-identical, biologically-related, donor-recipient pairs...