Allogeneic hematopoietic stem cell transplantation (alloHSCT) from mismatched unrelated donors (MMUD) carries high risks of non-relapse mortality (NRM) and graft-versus-host disease (GVHD). Post-transplant cyclophosphamide (PTCY) has emerged as an alternative to antithymocyte globulin (ATG) for GVHD prophylaxis. This single-center retrospective study compared PTCY (n=41) to high-dose ATG and low-dose ATG in 155 MMUD alloHSCT recipients.
View Article and Find Full Text PDFWe assessed whether the incidence and outcomes of chronic Graft-versus-Host Disease (cGvHD) after allogeneic hematopoietic stem cell transplantation (alloHSCT) have changed over 30 years. We studied 102,275 adults with hematological malignancies receiving a first alloHSCT from identical siblings or unrelated donors. We compared 3 decades: (I) 1990-1999 vs.
View Article and Find Full Text PDFJ Exp Med
September 2025
Acute graft-versus-host disease (aGVHD) can affect the central nervous system (CNS) through microglial activation and T cell infiltration, but the role of gut microbiota in CNS-aGVHD remains unclear. Here, we investigated the role of microbiota in microglial activation during aGVHD using antibiotic-treated specific pathogen-free (SPF), germ-free (GF), and wildling mice. Antibiotic-mediated microbiota depletion led to infiltration of IFN-γ-producing T cells in the brain, activation of microglia via the TLR4/p38 MAPK pathway, and neurocognitive deficits in SPF aGVHD mice.
View Article and Find Full Text PDFAm J Respir Crit Care Med
August 2025
Bronchiolitis obliterans syndrome (BOS) is a late-onset noninfectious pulmonary complication of allogeneic hematopoietic cell transplant (HCT) that is often diagnosed at an advanced stage with severe lung impairment. Increasing use of HCT for the treatment of hematologic diseases worldwide translates to an increasing burden of BOS, particularly for the community pulmonologist. Early recognition of BOS, which offers the best opportunity to mitigate morbidity and mortality, is hampered by incomplete knowledge of the clinical course and disease process.
View Article and Find Full Text PDFCutaneous T-cell lymphomas (CTCLs) are rare, usually refractory, and sometimes fatal diseases. Patients presenting with advanced-stage CTCL usually exhibit poor long-term survival outcomes. Only very few treatments have improved progression-free survival (PFS) in advanced CTCL, and no treatment has increased overall survival (OS).
View Article and Find Full Text PDFTransfus Clin Biol
August 2025
Background: After allogeneic hematopoietic stem cell transplantation (alloHSCT), the HAS recommends transfusing red blood cells (RBCs) matched for Rh ("Rhesus") phenotypes, and the EFS recommends respecting both donor and recipient Rh phenotypes. We previously reported a 10.3% allo-immunization rate in 58 Rh-incompatible alloHSCT recipients transfused in the donor phenotype: none was directed against the mismatched donor Rh antigens.
View Article and Find Full Text PDFBackground: Chronic cutaneous graft-versus-host disease (ccGVHD) is a debilitating complication of allogeneic haematopoietic stem cell transplantation, manifesting as either sclerotic or lichenoid eruptions (lGVHD). Although frequent, the pathogenesis of lGVHD remains mainly unknown and represents a therapeutic challenge.
Objectives: This study aims to decipher the immunological mechanisms underlying lichenoid GVHD and to evaluate the effect of blocking the Type I interferons (IFN-I) pathway in a mice model of ccGVHD on local inflammation.
Cancer Immunol Immunother
April 2025
Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by marrow fibrosis, splenomegaly, constitutional symptoms and cytopenia with a proinflammatory and profibrotic cytokine phenotype involving the JAK-STAT pathway. Ruxolitinib is a JAK 1/2 inhibitor with proven efficacy on splenomegaly and constitutional symptoms, but it does not reverse fibrosis or the risk of leukemic transformation. While hematopoietic stem cell transplantation remains the only curative approach, it is still associated with a relatively high non-relapse mortality (NRM) rate, partly due to GVHD.
View Article and Find Full Text PDFIntestinal glucocorticoid-refractory (SR) acute (a) graft-versus-host disease (GVHD) causes high non-relapse mortality (NRM) in patients after allogeneic hematopoietic cell transplantation (allo-HCT). Recent preclinical data indicate that acute GVHD causes a loss of intestinal neuroendocrine L-cells leading to reduced levels of glucagon-like peptide-2 (GLP-2). GLP-2 substitution improved GVHD severity and increased Paneth cells and intestinal stem cells in mice.
View Article and Find Full Text PDFChronic graft versus host disease is a major cause of morbidity after allogeneic haematopoietic cell transplantation. Belumosudil has recently been approved for the treatment of cGVHD refractory after two lines of treatment. However, few data are available to evaluate its efficacy and safety in real life.
View Article and Find Full Text PDFAcute graft-versus-host disease (GVHD) that occurs after allogeneic hematopoietic cell transplantation (allo-HCT) can affect the central nervous system (CNS). Most patients who have undergone allo-HCT receive antibiotic treatment, which alters the microbiome and essential microbiome-derived metabolites. We investigated the impact of microbiome modifications on CNS GVHD and therapeutic strategies to overcome the microbiome-derived metabolite depletion.
View Article and Find Full Text PDFDonor lymphocyte infusion (DLI) prevents acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) relapses following hematopoietic stem cell transplantation. Given the life-threatening toxicities such as graft versus host disease (GVHD), the identification of variables associated with response without toxicities is warranted. We hypothesized that HLA evolutionary divergence (HED), defined by the diversity between two given alleles of the same HLA gene, may be such a factor.
View Article and Find Full Text PDFAm J Hematol
February 2025
The objective of this meta-analysis (MA) was to evaluate the efficacy and safety of extracorporeal photopheresis (ECP) for the treatment of steroid-refractory chronic graft-versus-host disease (SR-cGvHD). A systematic literature review (SLR) was conducted according to PRISMA guidelines, followed by a feasibility assessment (FA) to assess potential between-study heterogeneity in the meta-analysis (MA). Random-effects MAs were performed for overall survival (OS), failure-free survival (FFS), overall response rate (ORR) and skin-specific response.
View Article and Find Full Text PDFDespite the growing evidence supporting the existence of CNS involvement in acute and chronic graft-versus-host disease (CNS-GvHD), the characteristics and course of the disease are still largely unknown. In this multicentre retrospective study, we analysed the clinical, biological, radiological and histopathological characteristics, as well as the clinical course of 66 patients diagnosed with possible CNS-GvHD (pCNS-GvHD), selected by predetermined diagnostic criteria. Results were then contrasted depending on whether pCNS-GvHD onset occurred before or after Day 100 following allogeneic haematopoietic stem cell transplantation (allo-HSCT).
View Article and Find Full Text PDFHaematologica
October 2024
Acute graft-versus-host disease (aGVHD) remains a barrier to successful allogeneic hematopoietic stem cell transplantation (HSCT) outcomes. Contemporary comprehensive analyses of real-world clinical outcomes among patients who develop aGVHD post-HSCT are needed to better understand the unmet needs of this patient population. This multicenter, retrospective chart review describes treatment patterns and clinical outcomes among patients (≥18 years old) from Finland, Sweden, and France who developed grades II-IV aGVHD after their first HSCT (January 2016-June 2017).
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