Severe corneal manifestations of graft-versus-host disease: experience of a tertiary referral center.

Purpose: Graft-versus-host disease (GVHD) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). GVHD may affect several organs, including ocular manifestations, ranging from dry eye syndrome to sight-threatening corneal ulceration or perforation. Limited information is available about characteristics and treatments of ocular GVHD and its relation to general prognosis.

Efficacy of Ruxolitinib in the management of chronic GVHD.

Objectives: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for hematological diseases, with success rates improving due to advancements in conditioning regimens and new anti-graft versus host disease (GVHD) drugs. Ruxolitinib, an oral selective Janus kinase (JAK) 1 and 2 inhibitor has been used to mitigate the effects of various inflammatory and myeloproliferative syndromes, given the JAK kinase pathway's central role in cytokine signaling during inflammatory and immune processes. In this study we aimed to assess ruxolitinib's efficacy in patients with chronic GVHD (cGVHD).

Effectiveness of ibrutinib in the management of chronic GVHD.

Objectives: Chronic graft-versus-host disease (cGVHD) represents a significant adverse event that may ensue following allogeneic hematopoietic stem cell transplantation (Allo-HSCT). In patients resistant to corticosteroids, which is the first-line treatment for cGVHD, ibrutinib is being evaluated as a potential treatment option. In this study, we aimed to share the findings of our multicenter study regarding the outcomes of ibrutinib treatment in patients with corticosteroid-resistant cGVHD who had previously received multiple systemic therapies.

Howell-Jolly Body-Like Neutrophil Inclusions Following Hematopoietic Stem Cell Transplantation: A Case Report.

BACKGROUND In several studies, the presence of Howell-Jolly body-like inclusions within neutrophils has been observed in cases of HIV infection, SARS-CoV-2 infection, post-transplant immunosuppression, and during chemotherapy or antiviral therapy. The phenomenon of neutrophils exhibiting Howell-Jolly body-like inclusions on peripheral blood smears can be attributable to viral infections or the pharmacological effects of medications. CASE REPORT A 14-year-old male patient who had received a diagnosis of lymphoblastic leukemia a year ago underwent hematopoietic stem cell transplantation and was readmitted due to a recurrence of gastrointestinal graft-versus-host disease (GVHD).

Modified G-CSF/ATG-Based Haploidentical Transplantation Protocol in Pediatric Primary Hemophagocytic Lymphohistiocytosis: A Long-Term Follow-Up Single-Center Experience.

Background: Primary hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome caused by immune dysregulation. Hematopoietic stem cell transplantation (HSCT) represents the only option for long-term cure for primary HLH. However, only around 25% of patients have a fully HLA-matched donor.

Semimechanistic Population PK/PD Modeling of Axatilimab in Healthy Participants and Patients With Solid Tumors or Chronic Graft-Versus-Host Disease.

Axatilimab, a high-affinity humanized immunoglobulin G4 monoclonal antibody against colony-stimulating factor 1 receptor (CSF-1R), is approved for the treatment of chronic graft-versus-host disease (cGVHD), and under investigation for idiopathic pulmonary fibrosis and solid tumors. The population pharmacokinetics (PK) and pharmacodynamics (PD) of axatilimab were characterized in healthy participants and patients with solid tumors or cGVHD using data from four clinical studies with 325 participants, including 278 patients with cGVHD. The model structure reflected the mechanism of action of axatilimab: blocking CSF-1R signaling with axatilimab reduces the circulating levels of cells in the mononuclear phagocytic cell lineage (including nonclassical monocytic cells (NCMCs) and Kupffer cells), resulting in increases in circulating enzymes owing to reduced clearance by Kupffer cells.

Allogeneic Stem Cell Transplant in Hematological Disorders: A Decade of Experience.

: Allogeneic hematopoietic cell transplantation (allo-HCT) is a complex procedure with the potential to provide curative treatment for various hematological disorders. This study aims to evaluate the outcomes of allo-HCT in hematological diseases and identify significant complications in a single-center setting. : We conducted a retrospective analysis of 180 patients with hematological diseases who underwent allo-HCT between January 2011 and December 2021.

Comparison of fludarabine/melphalan (FM140) with fludarabine/melphalan/BCNU (FBM110) in patients with relapsed/refractory AML undergoing allogeneic hematopoietic cell transplantation - a registry study on behalf of the EBMT Acute Leukemia Working Party.

The treatment of relapsed/refractory acute myeloid leukemia (AML) is associated with a dismal prognosis. The allogeneic hematopoietic cell transplantation (allo-HCT) is frequently performed as salvage therapy. Reduced intensity conditioning protocols have been developed with the aim of reducing the leukemia burden without increasing their toxicity.

A phase 2 pilot study of umbilical cord blood infusion as an adjuvant consolidation therapy in elderly patients with acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aging-related malignancy, with patients aged ≥60 years old facing significantly poorer prognosis. Umbilical cord blood (UCB) has emerged as a promising source with effective anti-aging roles. Here, we conducted a prospective, phase 2, single-arm trial of UCB infusion as an adjuvant consolidation therapy in elderly AML patients (ChiCTR-OPC-15006492).

Lipid levels increase to the normal range after nonmyeloablative hematopoietic cell transplantation for sickle cell disease.

Background: Individuals with sickle cell disease (SCD) have a unique type of dyslipidemia characterized by low total cholesterol (TC), low low-density lipoprotein cholesterol (LDL-c), low high-density lipoprotein cholesterol (HDL-c), and normal triglycerides (TG). This lipid state is theorized to be cardioprotective against atherosclerosis. In SCD, hematopoietic cell transplant (HCT) offers a potentially curative therapy.

Incidence, risk factors, and outcomes of BK hemorrhagic cystitis in hematopoietic stem cell transplantation from HLA-matched and haploidentical donors with post-transplant cyclophosphamide.

Background: BK hemorrhagic cystitis (BK-HC) is a common complication following hematopoietic stem cell transplantation (HSCT), particularly when posttransplant cyclophosphamide (PTCy) is used as graft-versus-host disease (GVHD) prophylaxis. However, comparative studies of BK-HC incidence in matched sibling donors (MSD) and unrelated donors (MUD) often include small haploidentical (HAPLO) donor cohorts and usually lack detailed information on disease evolution, coinfections, management and impact on outcomes.

Objectives: This study aimed to evaluate the incidence, risk factors, and outcomes in patients with hematologic malignancies undergoing HSCT from MSD, MUD, HAPLO donors using PTCy as GVHD prophylaxis.

Pediatric Transplant and Cellular Therapy Consortium RESILIENT Conference on Pediatric Chronic Graft-Versus-Host Disease Survivorship After Hematopoietic Cell Transplantation: Part I. Phases of Chronic GVHD, Supportive Care, and Systemic Therapy Discontinuation.

Current literature lacks details on the impact of pediatric chronic graft-versus-host disease (cGVHD) on long-term survivorship after allogeneic hematopoietic cell transplantation (HCT). Nonetheless, cGVHD remains a leading cause of post-transplant morbidity and mortality in children and adolescents, which is particularly relevant given the longer life-expectancy after HCT (measured in decades) compared to older adults. To address this knowledge gap, leaders of the Pediatric Transplant and Cellular Therapy Consortium convened a multidisciplinary taskforce of experts in pediatric cGVHD and HCT late effects known as RESILIENT after Chronic GVHD (Research and Education towards Solutions for Late effects to Innovate, Excel, and Nurture after cGVHD).

What should be the optimal dose of post-transplantation cyclophosphamide for GVHD prophylaxis in allogeneic stem cell transplantation?

Objectives: In this study, we aimed to compare the engraftment days, graft versus host disease (GVHD) development, relapse and overall survival (OS) rates in patients using variable intensity conditioning regimens with two different post-transplant cyclophosphamide (PTCy) doses for hematological malignancies.

Material And Methods: We retrospectively analyzed 162 patients who have had PTCy at a dose of 25 mg/kg × 2 and 50 mg/kg × 2 between 2018 and 2024. Patients were divided in 2 groups; PTCy dose with 25 mg/kg × 2 (Group 1, n = 45) and PTCy dose with 50 mg/kg × 2 (Group 2, n = 117).

Post-transplant complications revealed by mycophenolate mofetil related transporters and metabolic enzymes gene polymorphisms in pediatric patients with hematological disorders.

Background: Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) serves as an important option for patients without an HLA matched donor in treating hematological disorders, while patients may experience various complications after transplantation. Mycophenolate mofetil (MMF), a cornerstone drug for graft-versus-host disease (GvHD) prophylaxis, effectively reduces the incidence of acute GvHD, and the efficacy of MMF varies among individuals associated with MMF-related transporters and metabolic enzymes single nucleotide polymorphisms (SNPs). However, limited studies have systematically reported the correlations between the MMF-related SNPs and post-transplant complications.

Inflammasomes: potential therapeutic targets in hematopoietic stem cell transplantation.

The realm of hematopoietic stem cell transplantation (HSCT) has witnessed remarkable advancements in elevating the cure and survival rates for patients with both malignant and non-malignant hematologic diseases. Nevertheless, a considerable number of patients continue to face challenges, including transplant-related complications, infection, graft failure, and mortality. Inflammasomes, the multi-protein complexes of the innate immune system, respond to various danger signals by releasing inflammatory cytokines and even mediating cell death.

Oral Inflammation and Microbiome Dysbiosis Exacerbate Chronic Graft-versus-host Disease.

The oral microbiota, second in abundance to the gut, is implicated in chronic systemic diseases, but its specific role in GVHD pathogenesis has been unclear. Our study finds that mucositis-induced oral dysbiosis in patients post-hematopoietic cell transplantation associated with increased chronic GVHD (cGVHD) even in patients receiving post-transplant cyclophosphamide. In murine HCT models, oral dysbiosis caused by bilateral molar ligatures exacerbated cGVHD and increased bacterial load in the oral cavity and gut with Enterococcaceae significantly increasing in both organs.

Incidence of and Risk Factors for Cutaneous Malignant Neoplasms After Blood or Marrow Transplant.

Importance: Cutaneous malignant neoplasms are the most common subsequent neoplasm after blood or marrow transplant (BMT), but a full assessment among survivors is lacking.

Objective: To identify risk factors for subsequent cutaneous malignant neoplasms using the BMT Survivor Study (BMTSS).

Design, Setting, And Participants: This retrospective cohort study included patients who underwent transplant from 1974 to 2014 at City of Hope, University of Minnesota, or University of Alabama at Birmingham and survived 2 years or longer, as well as a comparison cohort of siblings.

Early eosinophilia after hematopoietic stem cell transplantation is associated with chronic graft-versus-host disease.

Background: This study aimed to evaluate whether an early elevation of absolute eosinophil count after allogeneic hematopoietic stem cell transplantation (allo-HSCT) was associated with the development of chronic graft-versus-host disease (cGVHD) in children and adolescents.

Methods: A total of 165 consecutive patients who received allo-HSCT were included in the study. Patients who had previously received allo-HSCT, relapsed or died before Day 100, and did not achieve engraftment, were excluded.

Oral acute graft-versus-host disease.

Oral acute graft-versus-host disease (aGVHD) is rare and with no diagnostic criteria. We report a case of oral aGVHD with three clinical phases. A self-limited prodrome of largely subjective oral symptoms was followed by concurrent oral and upper gastrointestinal aGVHD.

A Two-Center Study of a Prognostic Model Related to Acute Kidney Injury After Allogeneic Hematopoietic Stem Cell Transplantation in Children: Development of a New Predictive Dynamic Nomogram.

Objectives: The purpose of this study was to develop a straightforward, easy-to-use online dynamic nomogram for the identification of children who are at high risk of developing acute kidney injury (AKI) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Methods: This was a two-center study in which 242 children in Henan Provincial Children's Hospital composed the training cohort, and 115 children in the First Affiliated Hospital of Zhengzhou University composed the validation cohort. Kaplan-Meier survival analysis was used to compare survival between children with nonacute kidney injury (NAKI) and children with AKI.

Interspecies transcriptome profiles of human T cell activation and liver inflammation in a xenogeneic graft-versus-host disease model.

Background: Xenogeneic transplantation induces acute graft-versus-host disease (aGvHD) and subsequent vital organ damage. Herein, we aimed to examine hepatic damage associated with aGvHD using histopathology and gene expression profiles.

Methods: A xenografic GvHD model was established by engrafting human peripheral blood mononuclear cells (PBMCs) into immunodeficient NOD-scid IL2Rγnull (NSG) mice after busulfan conditioning.

Combined Cytokine Blockade Therapy (CCBT) Using Basiliximab and Infliximab for Treatment of Steroid-Refractory Graft-Versus-Host Disease (SR-GvHD).

Background: The standard first-line treatment for acute graft-versus-host disease (aGvHD) is systemic, high-dose glucocorticoids which have historically had limited responses. Combined cytokine blockade therapy (CCBT) with the monoclonal antibodies infliximab (a TNF-α inhibitor) and basiliximab (an IL-2 receptor blocker) has had limited discussion in the literature.

Methods: Sixty patients with steroid-refractory aGVHD were analyzed.

Chronic Graft-versus-host Disease: Immune Insights, Therapeutic Advances, and Parallels for Solid Organ Transplantation.

Chronic graft-versus-host disease remains a frequent and morbid outcome of allogeneic hematopoietic cell transplantation, in which the donor-derived immune system attacks healthy recipient tissue. Preceding tissue damage mediated by chemoradiotherapy and alloreactive T cells compromise central and peripheral tolerance mechanisms, leading to aberrant donor T cell and germinal center B cell differentiation, culminating in pathogenic macrophage infiltration and differentiation in a target tissue, with ensuant fibrosis. This process results in a heterogeneous clinical syndrome with significant morbidity and mortality, frequently requiring prolonged therapy.