Graft versus host

Viral infections remain a major risk in immunocompromised pediatric patients, and virus-specific T cell (VST) therapy has been successful for treatment of refractory viral infections in prior studies. We performed a phase II multicenter study (NCT03475212) for the treatment of pediatric patients with inborn errors of immunity and/or post allogeneic hematopoietic stem cell transplant with refractory viral infections using partially-HLA matched VSTs targeting cytomegalovirus, Epstein-Barr virus, or adenovirus...

This study aimed to investigate the kinetics of immune recovery following umbilical cord blood transplantation (UCBT) in adults who received a myeloablative conditioning (MAC) regimen and antithymocyte globulin (ATG). While the immune recovery kinetics has been extensively studied in pediatric UCBT recipients, limited data exist for adults. We conducted a comprehensive analysis of 221 consecutive adult patients who underwent UCBT with MAC and ATG at a single institution. Our objective was to evaluate the influence of patient, disease, and transplant factors, along with acute graft-versus-host disease (aGVHD), on immune reconstitution and overall survival...

Allogeneic hematopoietic cell transplantation (HCT) is used to treat many blood-based disorders and malignancies, however it can also result in serious adverse events, such as the development of acute graft-versus-host disease (aGVHD). This study aimed to develop a donor-specific epigenetic classifier to reduce incidence of aGVHD by improving donor selection. Genome-wide DNA methylation was assessed in a discovery cohort of 288 HCT donors selected based on recipient aGVHD outcome; this cohort consisted of 144 cases with aGVHD grades III-IV and 144 controls with no aGVHD...

A literature review does not provide information about the safety of autologous hematopoietic stem cell transplantation (HSCT) in a recipient who has previously received allogeneic HSCT. We treated a 69-year-old woman with diffuse large B cell lymphoma. The patient received autologous stem cell transplantation (ASCT) in the second complete remission of malignant lymphoma. The patient had undergone allogeneic hematopoietic SCT (allo-HSCT) for chronic myeloid leukemia 20 years ago. Chronic myeloid leukemia had been in complete remission for the previous 20 years...

We herein present a fatal case of constrictive pericarditis (CP) due to acute myelomonocytic leukemia (AMML) in a patient who initially complained of an acute onset of chest pain two days after COVID-19 vaccination. An autopsy revealed pericardial infiltration of leukemic cells. CP is rarely associated with leukemia and only 14 cases have been reported in the literature. The etiology of CP in previous reports included leukemic infiltration, graft-versus-host disease, drug-induced, post-radiation, autoimmune, and otherwise unidentified...

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a pivotal treatment for high-risk acute lymphocytic leukemia (ALL), although limited by suitable human leukocyte antigen (HLA)-matched sibling donors (MSD). This study evaluates the impact of donor selection on outcomes in post-HSCT Hispanic B-cell ALL patients. METHODOLOGY: This single-center retrospective study evaluates outcomes in 88 adult Hispanic B-cell ALL patients who underwent haploidentical, MSD, or MUD myeloablative HSCT between 2013 and 2023...

Systemic antifungal therapy is critical for reducing the mortality from many invasive and chronic fungal infections. Triazole antifungals are the most frequently prescribed antifungals but require attention to dosing and drug interactions. Nearly 600 severe drug-drug interactions and over 1100 moderate interactions requiring dose modifications are described or anticipated with systemic antifungal agents (see https://www.aspergillus.org.uk/antifungal-drug-interactions/). In this article, we address the common and less common, but serious, drug interactions observed in clinical practice with triazole antifungals, including a group of drugs that cannot be prescribed with all or most triazole antifungals (ivabradine, ranolazine, eplerenone, fentanyl, apomorphine, quetiapine, bedaquiline, rifampicin, rifabutin, sirolimus, phenytoin and carbamazepine)...

Optimizing natural killer (NK) cell alloreactivity could further improve outcome after allogeneic hematopoietic cell transplantation (alloHCT). The donor's Killer-cell Immunoglobulin-like Receptor (KIR) genotype may provide important information in this regard. In the past decade, different models have been proposed aiming at maximizing NK cell activation by activating KIR-ligand interactions or minimizing inhibitory KIR-ligand interactions. Alternative classifications intended predicting outcome after alloHCT by donor KIR-haplotypes...

The adoptive transfer of regulatory T cells is a promising strategy to prevent graft-versus-host disease after allogeneic bone marrow transplantation. Here, we use a major histocompatibility complex-mismatched mouse model to follow the fate of in vitro expanded donor regulatory T cells upon migration to target organs. Employing comprehensive gene expression and repertoire profiling, we show that they retain their suppressive function and plasticity after transfer. Upon entering non-lymphoid tissues, donor regulatory T cells acquire organ-specific gene expression profiles resembling tissue-resident cells and activate hallmark suppressive and cytotoxic pathways, most evidently in the colon, when co-transplanted with graft-versus-host disease-inducing conventional T cells...

OBJECTIVES: To identify the prevalence and type of central venous access device-associated skin complications for adult cancer patients, describe central venous access device management practices, and identify clinical and demographic characteristics associated with risk of central venous access device-associated skin complications. METHODS: A prospective cohort study of 369 patients (626 central venous access devices; 7,682 catheter days) was undertaken between March 2017 and March 2018 across two cancer care in-patient units in a large teaching hospital...

OBJECTIVE: Photobiomodulation (PBM) therapy is recommended by multiple international societies for managing oral mucositis (OM). These recommendations are based on extensive evidence. However, the search for an optimal PBM protocol continues. This mapping review focuses on a novel aspect of PBM therapy which is the immediate effect on pain levels associated with oral ulcerative conditions. DATA SOURCES: This literature review systematically compiles and evaluates the evidence about OM, alongside other oral ulcerative conditions, as the protocols that achieved pain relief for these oral conditions may have potential applicability to OM management...

Objective: To describe acute calcareous corneal degeneration as a complication of chronic graft-versus-host disease. Materials and methods: Clinical case and review of the literature. Results: We presented a case of bilateral acute calcareous corneal degeneration in a patient with chronic graft-versus-host disease. Conclusions: Chronic graft-versus-host disease (cGVHD) occurs in 50-70% of bone marrow transplantation patients, the most frequent ocular complication being keratoconjunctivitis sicca (KCS). Calcareous corneal degeneration is a type of calcium deposition that can be secondary to chronic ocular inflammation or dry eye, but there are few cases reported of acute calcareous corneal degeneration and recurrent perforation in cGVHD...

BACKGROUND: Conditioning regimens and the choice of immunosuppression have substantial impact on immune reconstitution after allogeneic hematopoietic stem cell transplantation (aHSCT). The pivotal mechanism to maintain remission is the induction of the graft-versus-tumor effect. Relapse as well as graft versus host disease remain common. Classic immunosuppressive strategies implementing calcineurin inhibitors (CNI) have significant toxicities, hamper the immune recovery, and reduce the anti-cancer immune response...

Post-transplant cyclophosphamide plus calcineurin inhibitor (CNI)(tacrolimus or cyclosporine A) plus mycophenolate mofetil (PTCy/TAC or CSA/MMF) and anti-thymocyte globulin plus CNI (tacrolimus or cyclosporine A) plus methotrexate (ATG/TAC or CSA/MTX) are common graft-versus-host disease (GVHD) prophylaxis regimens. We compared the two regimens in patients with acute myeloid leukemia (AML) undergoing allogeneic transplantation from matched siblings or unrelated donors. 402 received PTCy/TAC or CSA/MMF and 5648 received ATG/TAC or CSA/MTX...

Bruton tyrosine kinases (BTKs) play critical roles in various diseases, including chronic lymphatic leukemia (CLL), Waldenström Macroglobulinemia, Marginal Zone Lymphoma, Mantle Cell Lymphoma (MCL), and Graft Versus Host diseases. BTKs are a family of tyrosine kinases involved in B lymphocyte signal transduction, development, and maturation. Their overexpression can lead to cancer as they are essential for the activation of the B Cell Receptor (BCR) signaling pathway. Blocking the activation of BTKs presents a promising approach for treating CLL...

Acute graft-versus-host disease (aGvHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). We performed RNA analysis of 1408 candidate genes in bone marrow samples obtained from 167 patients undergoing HSCT. RNA expression data were used in a machine learning algorithm to predict the presence or absence of aGvHD using either random forest or extreme gradient boosting algorithms. Patients were randomly divided into training (2/3 of patients) and validation (1/3 of patients) sets...

Graft-versus-host disease (GVHD), an adverse effect after bone marrow transplantation (BMT), may affect male reproductive function. It is hypothesized that a sex-mismatched BMT induces GVHD in male reproductive organs because female immune cells are not immunologically tolerant to specific antigens of the male organs. However, this hypothesis has not been experimentally verified using male (M) recipient animals following BMT from the female (F) donors. Therefore, the aim of the present study is to examine whether the female BMT to males (F→M group) induces some GVHD reactions in the testis and the other male reproductive organs...

The introduction of posttransplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis lead to significant improvements in haploidentical stem cell transplantation (haplo-SCT) outcomes over the past decade. We retrospectively assessed long-term outcomes of patients who had their first haplo-SCT between February 2009 and March 2019. Long-term survivors were defined as patients who were alive and disease free at 2 years after transplant. Three hundred thirty-five patients with a median age of 48 (range, 18-72) years were identified...

BACKGROUND: Real-world data on outcomes of upfront allogeneic hematopoietic stem cell transplantation (allo-HCT) for adult T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) patients in first complete remission (CR1) is still lacking. METHODS: A single center retrospective study was conducted from 94 consecutive patients received their first allo-HCT between 2010 and 2021, which include 76 patients received upfront allo-HCT and 18 patients received allo-HCT in non-upfront settings...

BACKGROUND: Despite recent advances in immunotherapy, a substantial population of late-stage melanoma patients still fail to achieve sustained clinical benefit. Lack of translational preclinical models continues to be a major challenge in the field of immunotherapy; thus, more optimized translational models could strongly influence clinical trial development. To address this unmet need, we designed a preclinical model reflecting the heterogeneity in melanoma patients' clinical responses that can be used to evaluate novel immunotherapies and synergistic combinatorial treatment strategies...