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18 pages, 2396 KB  
Article
A Distinct Intestinal Domination Fingerprint in Patients Undergoing Allo-HSCT: Dynamics, Predictors and Implications on Clinical Outcomes
by Alexandre Soares Ferreira Junior, Danielle Amanda Niz Alvarez, Larissa da Silva Souza, Nathalia Linares Silva, Luiza Dias Machado, Welinton Yoshio Hirai, Rozana Mesquita Ciconelli, Joao Victor Piccolo Feliciano, Iago Colturato, George Maurício Navarro Barros, Phillip Scheinberg, Nelson Jen An. Chao and Gislane Lelis Vilela de Oliveira
J. Clin. Med. 2025, 14(23), 8351; https://doi.org/10.3390/jcm14238351 - 24 Nov 2025
Viewed by 231
Abstract
Background: Although Enterococcus domination has been extensively evaluated in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT), the prevalence and clinical implications of other dominant genera remain poorly understood. Objective: In this study, we sought to determine the dynamics, predictors and [...] Read more.
Background: Although Enterococcus domination has been extensively evaluated in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT), the prevalence and clinical implications of other dominant genera remain poorly understood. Objective: In this study, we sought to determine the dynamics, predictors and clinical implications of intestinal domination in Brazilian patients undergoing allo-HSCT. Methods: In a prospective study of four Brazilian centers, fecal specimens were collected longitudinally prior to allo-HSCT until six months post-transplantation. To identify intestinal domination, we performed 16S rRNA gene sequencing using the Illumina platform. We then evaluated the impact of intestinal domination on overall survival and acute Graft-versus-Host-Disease (aGvHD) incidence. Finally, to identify predictors of intestinal domination, we performed a logistic regression model. Results: A total of 192 fecal specimens were collected from 69 patients. No significant changes in alpha or beta diversity were observed over the course of allo-HSCT. Among the 192 specimens, 131 (68%) presented intestinal domination. The top four dominant genera were Bacteroides, Akkermansia, Phascolarctobacterium, and Escherichia-Shigella. No significant associations were found between domination by these genera and either overall survival or aGvHD incidence. Furthermore, no patient-level characteristics, including age, sex, underlying disease, conditioning regimen, or stem cell source, reliably predicted intestinal domination. Conclusions: Our findings reveal a unique intestinal domination fingerprint in Brazilian patients and highlight the importance of geographic context in interpreting microbiota–outcome associations in allo-HSCT settings. Full article
(This article belongs to the Special Issue Clinical Updates in Stem Cell Transplants)
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11 pages, 475 KB  
Article
Treosulfan-Based Conditioning Regimens for Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia and Other Myeloid Malignancies
by Eleni Gavriilaki, Panagiotis Dolgyras, Ioannis Konstantinidis, Despina Mallouri, Grigorios Salvaras, Christos Demosthenous, Ioannis Batsis, Anna Vardi, Ioannis Papadopoulos, Sophia Tsokkou, Zoi Bousiou, Giorgos Karavalakis, Christos Varelas, Alkistis Panteliadou, Nikolaos Spyridis, Antonia Syrigou, Anastasia Marvaki, Maria Papathanasiou, Apostolia Papalexandri, Chrysavgi Lalayanni, Chrysanthi Vadikoliou, Anastasia Athanasiadou and Ioanna Sakellariadd Show full author list remove Hide full author list
Pharmaceuticals 2025, 18(11), 1631; https://doi.org/10.3390/ph18111631 - 29 Oct 2025
Viewed by 534
Abstract
Background: Treosulfan combined with fludarabine (FluTreo) has emerged as a reduced-toxicity alternative to conventional myeloablative conditioning in allogeneic hematopoietic cell transplantation (allo-HCT) for acute myeloid leukemia (AML) and related myeloid malignancies. Purpose: This study evaluates the safety, engraftment kinetics, and long-term outcomes of [...] Read more.
Background: Treosulfan combined with fludarabine (FluTreo) has emerged as a reduced-toxicity alternative to conventional myeloablative conditioning in allogeneic hematopoietic cell transplantation (allo-HCT) for acute myeloid leukemia (AML) and related myeloid malignancies. Purpose: This study evaluates the safety, engraftment kinetics, and long-term outcomes of the FluTreo FT14 regimen in a real-world adult cohort. Materials and Methods: We conducted a prospective cohort study of 186 consecutive adults (18–70 years) undergoing allo-HCT between January 2015 and December 2024. Eligible diagnoses included de novo or secondary AML, myelodysplastic syndrome, and myelofibrosis. All received peripheral blood stem cells from matched or mismatched unrelated donors, HLA-matched siblings, or haploidentical relatives. The FT14 protocol comprised fludarabine 150 mg/m2 over five days and treosulfan 42 g/m2 over three days, with rabbit antithymocyte globulin (5 mg/kg) for unrelated grafts. Primary endpoints were neutrophil and platelet engraftment, donor chimerism, incidence of acute and chronic graft-versus-host disease (GVHD), overall survival (OS), disease-free survival (DFS), relapse, and treatment-related mortality (TRM). Kaplan–Meier, Cox regression, and Fine and Gray models were applied. Results: Median age was 59 years; diagnoses included de novo AML (43%), secondary AML (16%), MDS (25%), and MF (16%). Neutrophil and platelet engraftment medians were 10 and 12 days, respectively. Full donor chimerism (≥99%) was achieved by day 31. Grade III conditioning-related toxicity occurred in 3.2% of cases. Five-year cumulative incidences of grade II–IV acute GVHD and moderate/severe chronic GVHD were 37.6% and 30.6%. Median follow-up was 16.3 months; relapse occurred in 25.3%. Five-year OS and DFS were 71% and 49% overall (75.8% and 59% in CR1), with TRM of 15.3%. Disease relapse and acute GVHD independently predicted inferior OS, and acute GVHD predicted TRM. Conclusions: The FluTreo FT14 regimen achieves rapid engraftment, universal high donor chimerism, low severe toxicity, and durable survival, supporting its use as a myeloablative, reduced-toxicity conditioning option in myeloid malignancies. Full article
(This article belongs to the Section Pharmacology)
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18 pages, 456 KB  
Review
Allogeneic Hematopoietic Stem Cell Transplantation for Infant Leukemia: A Single-Center Case Series and Narrative Review
by Irina Kostareva, Kirill Kirgizov, Irina Shubina, Nara Stepanyan, Nataliya Batmanova, Timur Valiev, Mihail Kiselevsky and Svetlana Varfolomeeva
Children 2025, 12(10), 1418; https://doi.org/10.3390/children12101418 - 20 Oct 2025
Viewed by 677
Abstract
Background/Objectives: Acute leukemias (AL) in children under 1-year-old are combined under the term “infant leukemia” and are a very rare malignancies, accounting for up to 5% of all childhood AL cases. The predominance of unfavorable clinical and laboratory characteristics leads to unsatisfactory treatment [...] Read more.
Background/Objectives: Acute leukemias (AL) in children under 1-year-old are combined under the term “infant leukemia” and are a very rare malignancies, accounting for up to 5% of all childhood AL cases. The predominance of unfavorable clinical and laboratory characteristics leads to unsatisfactory treatment results, even with the use of modern treatment protocols. Patients/Methods: A comprehensive search through MEDLINE, PubMed, Scopus, and ScienceDirect using infant leukemia-related keywords was performed and included a final set of 52 academic articles. Our own experience included 11 patients with infant leukemia underwent allo-HSCT (allogeneic hematopoietic stem cell transplantation) at the NN Blokhin National Medical Research Center of Oncology in 2021–2023. Types of leukemia included acute myeloid leukemia, lymphoblastic leukemia, and mixed-phenotype acute leukemia. The most frequent cytogenetic aberration was KMT2A. All patients were in clinical and hematological remission, but four had positive MRD status (minimal residual disease). Donors: haploidentical—5 (45.4%), matched unrelated donor—5 (45.4%), and matched related donor—1 (9.2%). Graft manipulations: post-transplant cyclophosphamide was given to three patients with haplo-HSCT, and TCRαβ/CD19 depletion was performed in two patients. The type of immunosuppressive therapy (IST) varied based on the donor. Conditioning regimens were myeloablative. Results: Median follow-up was 23.5 months. Acute GVHD grade I–II developed in two patients (18%) and grade III–IV in three patients (27%). The overall survival rate was 54.5% (n = 6). The relapse rate after allo-HSCT was 18% (n = 2). The most common cause of treatment failure was infectious complications in the early post-transplant period (70%). Conclusions: Our center’s experience demonstrated acceptable transplant-related mortality and satisfactory relapse rates after allo-HSCT in patients with infant leukemia. The treatment of acute leukemia in infants is challenging, and optimal protocols are being developed around the world specifically for these patients. Taking into account the characteristics of this age group, the choice of chemotherapy drug doses should be carefully considered, and the indications for allo-HSCT should be balanced. Full article
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15 pages, 1389 KB  
Article
Safety of Post-Transplant Cyclophosphamide-Based Prophylaxis in AML Patients with Pre-Existing Cardiac Morbidity Undergoing Allogeneic Hematopoietic Cell Transplantation
by Arnau Torrent-Rodríguez, Enric Cascos, Víctor Navarro Garcés, Estefanía Pérez-López, Mónica Baile-González, Carlos Martín Rodríguez, María Jesús Pascual Cascón, Marta Luque, Albert Esquirol, Carmen Martín Calvo, Felipe Peña-Muñoz, Inmaculada Heras Fernando, Itziar Oiartzabal Ormtegi, Adolfo Jesús Sáez Marín, Sara Fernández-Luis, Juan José Domínguez-García, Sara Villar Fernández, José Luis López Lorenzo, Miguel Fernández de Sanmamed Girón, Leslie González Pinedo, Lucía García-Maño, Ana Pilar González-Rodriguez, Tamara Torrado, Silvia Filaferro, Pascual Basalobre, Guillermo Ortí, Montserrat Rovira, Manuel Jurado Chacón and María Queralt Salasadd Show full author list remove Hide full author list
Cancers 2025, 17(19), 3128; https://doi.org/10.3390/cancers17193128 - 26 Sep 2025
Viewed by 629
Abstract
Background: Post-transplant cyclophosphamide (PTCy) is a standard graft-versus-host disease (GVHD) prophylaxis in allogeneic hematopoietic cell transplantation (allo-HCT). While effective, concerns remain about cyclophosphamide-related cardiotoxicity, especially in patients with pre-existing cardiac morbidity, a population often underrepresented in clinical trials. Objectives: To assess the incidence [...] Read more.
Background: Post-transplant cyclophosphamide (PTCy) is a standard graft-versus-host disease (GVHD) prophylaxis in allogeneic hematopoietic cell transplantation (allo-HCT). While effective, concerns remain about cyclophosphamide-related cardiotoxicity, especially in patients with pre-existing cardiac morbidity, a population often underrepresented in clinical trials. Objectives: To assess the incidence and outcomes of early (ECE, ≤100 days) and late (LCE, >100 days) cardiac events in acute myeloid leukemia (AML) patients with and without baseline cardiac morbidity undergoing allo-HCT with PTCy. Study Design: Retrospective multicenter study by the Grupo Español de Trasplante Hematopoyético y Terapia Celular (GETH-TC) including 461 AML patients (62 with cardiac morbidity) transplanted between 2012 and 2022. Cardiac morbidity was defined by documented cardiac disease or left ventricular ejection fraction < 45%. Cumulative incidence, overall survival (OS), and non-relapse mortality (NRM) were analyzed using competing risks models and adjusted with propensity score matching (PSM) and inverse probability weighting (IPW). Results: Cardiac events occurred in 13.2% of patients: 11% vs. 7% ECE (p = 0.93) and 8% vs. 5.3% LCE (p = 0.85) in those with vs. without cardiac morbidity. Most ECEs were arrhythmias or heart failure. Adjusted analyses confirmed no significant differences in CE incidence, OS, or NRM between groups. Two-year OS was 69% vs. 70% (p = 0.50); NRM was 18% vs. 17% (p = 0.20). ECE was associated with higher mortality in both groups. Conclusions: PTCy is feasible in AML patients with pre-existing cardiac morbidity when combined with comprehensive cardiovascular evaluation and cardio-oncology follow-up, supporting its safe use in broader patient populations with appropriate cardiologic support. Full article
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10 pages, 932 KB  
Article
Potential Impact of HLA DQB1*05 on Identical Sibling Hematopoietic Stem Cell Transplantation Outcome
by Fatma Al Lawati, Murtadha Al Khabori, Salma Al Harrasi and Aliya Al Ansari
J. Clin. Med. 2025, 14(19), 6798; https://doi.org/10.3390/jcm14196798 - 26 Sep 2025
Viewed by 468
Abstract
Background/Objectives: Human leukocyte antigens (HLAs) are major determinants of successful allogeneic hematopoietic stem cell transplantation (allo-HSCT). Their alleles are closely linked to outcomes, even in HLA-identical sibling donor (ISD) HSCT. This retrospective study analyzed the impact of HLA alleles on HLA-ISD HSCT outcomes [...] Read more.
Background/Objectives: Human leukocyte antigens (HLAs) are major determinants of successful allogeneic hematopoietic stem cell transplantation (allo-HSCT). Their alleles are closely linked to outcomes, even in HLA-identical sibling donor (ISD) HSCT. This retrospective study analyzed the impact of HLA alleles on HLA-ISD HSCT outcomes in Omani patients. Methods: Data were collected for a heterogenous cohort of patients registered at the Sultan Qaboos University Hospital (SQUH), who underwent HLA-ISD HSCT from 2012 to 2022 (n = 153). HSCT outcomes, namely acute GVHD (aGVHD), chronic GVHD (cGVHD), chimerism status (complete or mixed) at 6 to 12 months after HSCT, neutrophil and platelet engraftment time, and patient five-year overall survival, were included. Low-resolution HLA-typing records were collected for five HLA loci: HLA-A, B, C, DRB1 and DQB1. GVHD and chimerism were analyzed by logistic regression analysis. Platelet and neutrophil engraftment times were assessed by Mann–Whitney tests. Patient overall survival was evaluated by the Kaplan–Meier model and Log-rank testing. At a 95% confidence interval, the p-value threshold was corrected using Bonferroni correction. Results: The incidence rates of aGVHD and cGVHD from all grades were 16% and 15%, respectively. Although no association between HLA alleles or any of the investigated outcomes was identified, survival curve analyses indicated a significant protective effect of HLA-DQB1*05 (p = 0.01). Patients carrying this allele had a better-estimated 5-year overall survival (90%) than did DQB1*05 negative patients (68%). Conclusions: This study suggests that HLA-DQB1*05 in the Omani population could have an impact on overall survival and might be a predictive biomarker. Further studies on a larger scale in other regional populations are needed to validate our findings and explore the underlying mechanism. Full article
(This article belongs to the Section Hematology)
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19 pages, 531 KB  
Systematic Review
A Systematic Review Evaluating the Impact of Fibre Supplementation on Gut Health and Other Clinical Outcomes in Adults with Haematological Malignancies During Haematopoietic Stem Cell Transplantation
by Fiona McCullough, Janice Cheung and Laura J. Miller
Nutrients 2025, 17(18), 2973; https://doi.org/10.3390/nu17182973 - 16 Sep 2025
Viewed by 809
Abstract
Background: Gut health is often disrupted in adults with haematological malignancies (HMs) receiving chemotherapy and haematopoietic stem cell transplantation (HCT). Microbial diversity is reduced, and both infection risk and inflammation increased. The role of dietary fibre in enhancing gut health, immune regulation, reducing [...] Read more.
Background: Gut health is often disrupted in adults with haematological malignancies (HMs) receiving chemotherapy and haematopoietic stem cell transplantation (HCT). Microbial diversity is reduced, and both infection risk and inflammation increased. The role of dietary fibre in enhancing gut health, immune regulation, reducing complications, and improving clinical outcomes for people with HMs shows promise but the extent of their role remains unclear. Objectives: This systematic review evaluated the role of dietary fibre supplementation in adults with HMs undergoing HCT on gut health, immune function, and gastrointestinal health. This included assessment of differences between fibre types. Methods: A systematic search of PubMed and EMBASE was conducted following PRISMA guidelines, independently by two reviewers. Study quality was assessed using the Newcastle–Ottawa scale (NOS). Results: Of the 5023 studies after de-duplication, 63 remained after abstract and title screening, 59 studies were full-text screened, 56 studies were excluded due to language (n = 6), wrong intervention (n = 25), wrong population (n = 4), or reporting on unrelated outcomes (n = 21), and 3 studies met all inclusion criteria. Interventions included fructooligosaccharides (FOS), resistant starch (RS), and a glutamine, fibre, and oligosaccharide (GFO) prebiotic blend. Despite heterogeneity in measured outcomes, positive impacts on gut health, immune function, and gastrointestinal health were shown. Conclusions: Fibre supplementation represents a promising adjunctive strategy to improve clinical outcomes in adults with HMs undergoing HCT, by improving microbial diversity, increasing short-chain fatty acid (SCFA) production, and reducing incidence of acute GVHD. Further research is needed to establish specific recommendations for fibre in the nutritional management of patients with HM. Full article
(This article belongs to the Special Issue Diet, Gut Health, and Clinical Nutrition)
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11 pages, 1264 KB  
Article
Impact of Iron Overload and Hypomagnesemia Combination on Pediatric Allogeneic Hematopoietic Stem Cell Transplantation Outcomes
by Debora Curci, Stefania Braidotti, Gilda Paternuosto, Anna Flamigni, Giulia Schillani, Antonella Longo, Nicole De Vita and Natalia Maximova
Nutrients 2025, 17(15), 2462; https://doi.org/10.3390/nu17152462 - 28 Jul 2025
Viewed by 749
Abstract
Background/Objectives: Pediatric allogeneic hematopoietic stem cell transplantation (allo-HSCT) is complicated by iron overload and hypomagnesemia, both contributing to immune dysfunction and post-transplant morbidity. The combined impact of these metabolic disturbances on pediatric allo-HSCT outcomes remains unexplored. This study aims to determine whether hypomagnesemia [...] Read more.
Background/Objectives: Pediatric allogeneic hematopoietic stem cell transplantation (allo-HSCT) is complicated by iron overload and hypomagnesemia, both contributing to immune dysfunction and post-transplant morbidity. The combined impact of these metabolic disturbances on pediatric allo-HSCT outcomes remains unexplored. This study aims to determine whether hypomagnesemia can serve as a prognostic biomarker for delayed immune reconstitution and explores its interplay with iron overload in predicting post-transplant complications and survival outcomes. Methods: A retrospective analysis was conducted on 163 pediatric allo-HSCT recipients. Serum magnesium levels were measured at defined intervals post-transplant, and outcomes were correlated with CD4+ T cell recovery, time to engraftment, incidence of graft-versus-host disease (GVHD), and survival within 12 months. Iron status, including siderosis severity, was evaluated using imaging and laboratory parameters obtained from clinical records. Results: Patients who died within 12 months post-transplant exhibited significantly lower magnesium levels. Hypomagnesemia was associated with delayed CD4+ T cell recovery, prolonged engraftment, and an increased risk of acute GVHD. A strong inverse correlation was observed between magnesium levels and the severity of siderosis. Iron overload appeared to exacerbate magnesium deficiency. Additionally, the coexistence of hypomagnesemia and siderosis significantly increased the risk of immune dysfunction and early mortality. No significant association was found with chronic GVHD. Conclusions: Hypomagnesemia is a significant, early predictor of poor outcomes in pediatric allo-HSCT, particularly in the context of iron overload, underscoring the need for early intervention, including iron chelation and MRI, to improve outcomes. Full article
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14 pages, 817 KB  
Article
Causes of Death in Childhood Acute Lymphoblastic Leukemia: A Single-Center Experience
by Matej Jelić, Maja Pavlović, Lucija Mucavac, Sara Dejanović Bekić, Zrinko Šalek, Toni Matić, Daniel Turudić, Luka Lovrenčić, Jelena Roganović and Ernest Bilić
Medicina 2025, 61(7), 1193; https://doi.org/10.3390/medicina61071193 - 30 Jun 2025
Viewed by 1214
Abstract
Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Good overall survival rates of about 90% are the result of improvements in risk stratification and risk-adapted therapy, intensive chemotherapy regimens, hematopoietic stem cell transplantation, and better supportive care. Background and Objectives [...] Read more.
Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Good overall survival rates of about 90% are the result of improvements in risk stratification and risk-adapted therapy, intensive chemotherapy regimens, hematopoietic stem cell transplantation, and better supportive care. Background and Objectives: The aim of this study is to review the epidemiology, prognostic factors, and causes of death in pediatric ALL patients treated at a tertiary care center, and to identify risk factors influencing clinical outcomes. Materials and Methods: A retrospective study was conducted at the Department of Pediatric Hematology and Oncology, University Hospital Centre Zagreb, including 302 children (0–18 years) diagnosed with ALL between January 2001 and December 2015. Results: Two hundred fifty-one children survived (5-year overall survival 83%). Relapse occurred in 13.6% of patients. Relapse rates were higher for B-cell precursor (Bcp)-ALL than for T-cell ALL (14.3% vs. 10.4%), and no patient with relapsed T-cell ALL survived. The main causes of death were refractory/relapsed disease (43% of patients), followed by infections (35%) and GVHD (8%). The most frequent causes of infectious death were Pseudomonas aeruginosa and Aspergillus fumigatus. The most critical treatment periods were the induction and reinduction phases, especially the de-escalation of corticosteroids. The time of relapse and risk group were independent factors in predicting the outcome. Conclusions: Relapse and infections were the leading causes of death in children with ALL, with the highest mortality observed during induction and reinduction phases. Survival was significantly influenced by relapse timing and risk group, with no survivors among relapsed T-ALL patients. Full article
(This article belongs to the Section Pediatrics)
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3 pages, 314 KB  
Interesting Images
Interesting Images: Endocytoscopy for In Vivo Diagnosis of Intestinal Graft-Versus-Host Disease
by Timo Rath, Till Orlemann, Francesco Vitali, Abbas Agaimy, Andreas Mackensen and Markus F. Neurath
Diagnostics 2025, 15(13), 1595; https://doi.org/10.3390/diagnostics15131595 - 24 Jun 2025
Viewed by 641
Abstract
Gastrointestinal graft-versus-host disease (GvHD) is a frequent and severe complication after allogeneic stem cell transplantation (aSCTx). Although biopsy and histopathology remain the gold standard for diagnosis of GvHD, this approach can be limited by thrombocytopenia accompanying aSCTx and the diagnostic delay associated with [...] Read more.
Gastrointestinal graft-versus-host disease (GvHD) is a frequent and severe complication after allogeneic stem cell transplantation (aSCTx). Although biopsy and histopathology remain the gold standard for diagnosis of GvHD, this approach can be limited by thrombocytopenia accompanying aSCTx and the diagnostic delay associated with routine histopathology. Here, we report on two patients in which dye-based contact microscopy using a latest generation endocytoscope with 520-fold magnification enabled in vivo diagnosis of GvHD. The first patient was a 23-year-old man with acute lymphoblastic leukemia presenting with non-bloody diarrhea 3 months after aSCTx. After topical staining with crystal violet and methylene blue, endocytoscopy in the rectum showed several apoptotic epithelial cells. Histopathology confirmed GvHD grade III according to the Lerner classification. The second patient was a 59-year-old female with diarrhea 3 months after aSCTx. Apart from pathognomic apoptotic bodies, EC additionally revealed crypt lumina enlargement and mononuclear cell infiltrates in the lamina propria with subsequent crypt distension. The duration of the procedure was less than 5 min in each patient. These findings illustrate that in vivo microscopy using endocytoscopy can enable instantaneous diagnosis of GvHD with the benefit of accelerating therapeutic decisions in patients with suspected severe GvHD. Full article
(This article belongs to the Special Issue Imaging Research on Gastrointestinal Disorders)
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13 pages, 612 KB  
Review
JAK2 Inhibitors and Emerging Therapies in Graft-Versus-Host Disease: Current Perspectives and Future Directions
by Behzad Amoozgar, Ayrton Bangolo, Abdifitah Mohamed, Charlene Mansour, Daniel Elias, Christina Cho and Siddhartha Reddy
Biomedicines 2025, 13(7), 1527; https://doi.org/10.3390/biomedicines13071527 - 23 Jun 2025
Cited by 1 | Viewed by 1810
Abstract
Graft-versus-host disease (GVHD) remains a significant barrier to the success of allogeneic hematopoietic stem cell transplantation (allo-HSCT), contributing to long-term morbidity and non-relapse mortality in both pediatric and adult populations. Central to GVHD pathophysiology is the Janus kinase (JAK)-signal transducer and activator of [...] Read more.
Graft-versus-host disease (GVHD) remains a significant barrier to the success of allogeneic hematopoietic stem cell transplantation (allo-HSCT), contributing to long-term morbidity and non-relapse mortality in both pediatric and adult populations. Central to GVHD pathophysiology is the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, where JAK2 mediates key pro-inflammatory cytokines, including IL-6, IFN-γ, and GM-CSF. These cytokines promote donor T cell activation, effector differentiation, and target organ damage. The introduction of ruxolitinib, a selective JAK1/2 inhibitor, has transformed the treatment landscape for steroid-refractory acute and chronic GVHD, leading to improved response rates and durable symptom control. However, its limitations—such as cytopenias, infectious complications, and incomplete responses—have catalyzed the development of next-generation agents. In 2024, the FDA approved axatilimab, a CSF-1R inhibitor that targets monocyte-derived macrophages in fibrotic chronic GVHD, and remestemcel-L, an allogeneic mesenchymal stromal cell therapy, for pediatric steroid-refractory acute GVHD. Both agents offer mechanistically distinct and clinically meaningful additions to the therapeutic armamentarium. In parallel, emerging combination strategies involving JAK2 inhibitors and novel biologics show promise in enhancing immune tolerance while preserving graft-versus-leukemia (GvL) effects. Recent advances in biomarker development, such as the MAGIC Algorithm Probability (MAP), are enabling early risk stratification and response prediction. The integration of these tools with organ-specific and personalized approaches marks a shift toward more precise, durable, and tolerable GVHD therapy. This review highlights the current state and future direction of JAK2 inhibition and complementary therapies in the evolving GVHD treatment paradigm. Full article
(This article belongs to the Special Issue An Update on Transplantation Immunology)
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13 pages, 461 KB  
Article
Post-Transplant Pain and Paralysis: Neurologic Amyotrophy as an Atypical Cause of Shoulder Dysfunction Following Hematopoietic Stem Cell Transplant
by Franchesca König, Chanel Davidoff, Katarzyna Ibanez, Sinchun Hwang, Ilan Goldstein, Darren R. Feldman, Boglarka Gyurkocza, Sergio A. Giralt, Ioannis Politikos, Doris M. Ponce, Michael Scordo, Grigory Syrkin, Christian M. Custodio and Gunjan L. Shah
Cancers 2025, 17(11), 1816; https://doi.org/10.3390/cancers17111816 - 29 May 2025
Cited by 1 | Viewed by 1344
Abstract
Background: Neuralgic amyotrophy (NA), also known as Parsonage–Turner syndrome, brachial neuritis, and idiopathic brachial plexopathy, is a rare and potentially debilitating peripheral nerve disorder characterized by acute-onset shoulder pain followed by progressive motor deficits. It is often under-recognized, with an estimated incidence of [...] Read more.
Background: Neuralgic amyotrophy (NA), also known as Parsonage–Turner syndrome, brachial neuritis, and idiopathic brachial plexopathy, is a rare and potentially debilitating peripheral nerve disorder characterized by acute-onset shoulder pain followed by progressive motor deficits. It is often under-recognized, with an estimated incidence of 1 to 3 per 100,000 annually, though some studies suggest the actual prevalence may be significantly higher. The condition typically progresses through three phases, an acute painful phase, a phase of weakness, and a recovery phase, with sensory disturbances common in addition to motor weakness. The exact pathogenesis of NA remains unclear, though it is thought to involve a combination of genetic, environmental, and immunological factors. While neurologic complications following hematopoietic stem cell transplantation (HSCT), such as neuropathies and myopathies, have been documented, NA remains exceedingly rare in this context, with only a few reported cases. The pathophysiology in HSCT patients is hypothesized to involve immune dysregulation, graft-versus-host disease (GvHD), infection, and the effects of immunosuppressive therapy. Diagnosis is primarily clinical, supported by electrodiagnostic studies and MRI, though no laboratory markers exist. The management of NA is largely supportive and multimodal, focusing on pain control and rehabilitation. Objectives: The objective of this study was to describe the characteristics, clinical course, and outcomes of patients admitted for HSCT who were subsequently diagnosed with NA. Study Design: This retrospective case series from a single institution examined nine (N = 9) patients who developed acute shoulder pain following HSCT. We collected data on demographics, transplant details, clinical features, MRI findings, and electrodiagnostic studies, summarized using descriptive statistics. The diagnosis of neurologic amyotrophy was based on clinical presentation and corroborated by imaging and electrodiagnostic results. Long-term follow-up was assessed to evaluate symptom recovery. Results: Between August 2020 and July 2022, nine patients (44% male, median age 60) were diagnosed with NA following autologous (n = 4) or allogeneic (n = 5) HSCT. The onset of severe shoulder pain occurred at a median of 9 days post-transplant (range 1–21 days), with the majority of patients experiencing unilateral pain, predominantly affecting the right shoulder (55%). Neurologic weakness developed on average 5.1 days after pain onset, and sensory deficits were observed in all but one patient. MRI findings revealed muscle edema, atrophy, and enhancement in six patients, while electromyography confirmed NA in five. Due to the small sample size, statistical analyses, including p-values, confidence intervals, and trend comparisons, were not performed, and thus no conclusions can be drawn regarding associations between variables such as early onset and worse outcomes. Shoulder pain resolved after a median of 23 days (range 8–40 days). Long-term follow-up (>1 year) showed that three patients achieved full or near-full recovery, four partially recovered, and two showed minimal improvement. Conclusions: NA should be highly suspected in patients with acute shoulder pain and neurologic symptoms post-HSCT. To improve diagnostic accuracy and clinical outcomes, we recommend enhanced clinician awareness, the implementation of targeted diagnostic protocols (such as MRI and electrodiagnostic studies), and the establishment of standardized long-term follow-up protocols. Full article
(This article belongs to the Special Issue Hematopoietic Stem-Cell Transplantation for Acute Myeloid Leukemia)
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12 pages, 724 KB  
Article
Allogeneic Hematopoietic Cell Transplant for B-Cell Lymphomas in the Era of Novel Cellular Therapies: Experience from a Tertiary Canadian Center
by Mathias Castonguay, Jean Roy, Jean-Sébastien Claveau, Sylvie Lachance, Jean-Sébastien Delisle, Thomas Kiss, Sandra Cohen, Isabelle Fleury, Luigina Mollica, Imran Ahmad, Nadia Bambace, Léa Bernard, Denis-Claude Roy, Guy Sauvageau and Olivier Veilleux
Curr. Oncol. 2025, 32(5), 285; https://doi.org/10.3390/curroncol32050285 - 20 May 2025
Viewed by 1145
Abstract
Background: Allogeneic hematopoietic cell transplant (alloHCT) is a curative option for relapsed/refractory B-cell lymphomas (BCLs), but its role in the evolving field of cellular therapy is increasingly unclear as recent advances in transplant procedures have improved outcomes. Methods: This retrospective, single-center study included [...] Read more.
Background: Allogeneic hematopoietic cell transplant (alloHCT) is a curative option for relapsed/refractory B-cell lymphomas (BCLs), but its role in the evolving field of cellular therapy is increasingly unclear as recent advances in transplant procedures have improved outcomes. Methods: This retrospective, single-center study included 55 BCL patients (large B-cell lymphoma—LBCL; indolent BCL; and mantle cell lymphoma—MCL) treated with alloHCT from 2015 to 2023 at Hôpital Maisonneuve-Rosemont. Primary endpoints were overall survival (OS) and progression-free survival (PFS); secondary endpoints included NRM and GVHD incidence. Results: A total of 55 patients were included (25 LBCLs, 16 indolent BCLs, 14 MCLs), and 76% of LBCLs were of indolent origin (Richter transformation, transformed follicular lymphoma). After a median follow-up of 6.1, 5.8 and 2.4 years for LBCLs, indolent BCLs and MCLs, their 5-year PFS and OS were 57.2% (IC 95%: 34.2–74.7) and 62.8% (IC 95%: 37.9–80.0), 81.2% (IC 95%: 52.5–93.5) and 93.8% (IC 95%: 63.2–99.1), and 39.0% (IC 95%: 14.3–63.3) and 68.1% (IC 95%: 35.4–86.8), respectively. The 5-year NRM was 16.9% (IC 95%: 8.2–28.3) with a relapse incidence of 23.4%. Overall/grade 3–4 acute GVHD occurred in 43.6% and 18.1% of patients. At 3 years, overall/moderate or severe chronic GVHD incidence was 49% and 34.5%. Conclusions: AlloHCT remains a potentially curative option and should be considered for fit patients with chemosensitive FL or LBCLs of indolent origin and a low comorbidity index. Full article
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15 pages, 990 KB  
Review
Healthcare Resource Use and Costs of Allogeneic Hematopoietic Stem Cell Transplantation Complications: A Scoping Review
by Nancy V. Kim, Gemma McErlean, Serena Yu, Ian Kerridge, Matthew Greenwood and Richard De Abreu Lourenco
Curr. Oncol. 2025, 32(5), 283; https://doi.org/10.3390/curroncol32050283 - 16 May 2025
Viewed by 1934
Abstract
Allogeneic hematopoietic stem cell transplant (allo-HSCT) is an expensive and resource intensive procedure. This study aims to review the literature pertaining to healthcare resource utilization (HRU) and costs associated with allo-HSCT complications. The review followed the Joanna Briggs Institute methodology for scoping reviews. [...] Read more.
Allogeneic hematopoietic stem cell transplant (allo-HSCT) is an expensive and resource intensive procedure. This study aims to review the literature pertaining to healthcare resource utilization (HRU) and costs associated with allo-HSCT complications. The review followed the Joanna Briggs Institute methodology for scoping reviews. The PubMed, EMBASE, and Health Business Elite were searched in addition to the grey literature. Eligibility criteria included studies that reported HRU and/or costs associated with adult (≥18 years) allo-HSCT. Studies were categorized according to complications of allo-HSCT including graft-versus-host disease (acute and chronic GVHD) and infections (fungal, cytomegalovirus, virus-associated hemorrhagic cystitis, and acute respiratory tract infection). Commonly reported HRU and cost measures were extracted, including those associated with the direct management of allo-HSCT complications and intensive care unit (ICU) admissions. Reported costs were standardized to 2022 United States Dollars. Patients who experienced GVHD or infection post-transplant had an overall greater HRU including higher rates of hospitalization, hospital readmission, ICU admission, and longer length of stay compared to those patients who did not. Patients with severe or refractory GVHD and/or infection following allo-HSCT required greater healthcare intervention. This scoping review synthesizes the current literature on HRU and costs associated with post allo-HSCT complications. Patients who experienced post allo-HSCT complications had higher HRU and incurred higher costs overall, noting the variability across studies in their clinical context, reporting of HRU, and cost measures. Full article
(This article belongs to the Section Cell Therapy)
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17 pages, 497 KB  
Article
Disease Burden at the Time of Transplantation Is a Primary Predictor of Outcomes in Pediatric MDS: A Single-Center Experience
by Ann Dahlberg, Phil Stevenson, Neel S. Bhatt, Lauri Burroughs, Paul A. Carpenter, Corinne Summers, Katherine Tarlock, Monica S. Thakar, Filippo Milano, H. Joachim Deeg and Marie Bleakley
Cancers 2025, 17(10), 1645; https://doi.org/10.3390/cancers17101645 - 13 May 2025
Viewed by 978
Abstract
Background: Hematopoietic cell transplantation (HCT) remains the only curative therapy for pediatric myelodysplastic syndrome (MDS) in all but rare cases. While HCT outcomes for pediatric MDS are similar across the largest registry and single-center trials, factors identified as contributing to inferior outcomes vary [...] Read more.
Background: Hematopoietic cell transplantation (HCT) remains the only curative therapy for pediatric myelodysplastic syndrome (MDS) in all but rare cases. While HCT outcomes for pediatric MDS are similar across the largest registry and single-center trials, factors identified as contributing to inferior outcomes vary from study to study. We performed an analysis to provide more clarity on the prognostic implications of disease characteristics, including blast burden and cytogenetic abnormalities, in the current era. Methods: We conducted a retrospective analysis of 36 consecutive children (<18 years of age at HCT) who underwent allogeneic HCT for MDS between June 2000 and October 2019 at the Fred Hutchinson Cancer Center. Results: Overall survival (OS) was 77% (95% CI 64–92%) and relapse-free survival (RFS) was 71% (95% CI 57–88%) at 2 years post-HCT. Patients with <5% blasts by morphology in the bone marrow at the time of HCT showed superior 2-year OS at 87% (95% CI 74–100%) as compared to 54% (95% CI 32–93%) in patients with ≥5% blasts, consistent with an HR of 4.6 (CI 1.14–18.7, p = 0.03). The inferior outcomes in patients with ≥5% blasts were due to increased relapse incidence (HR 7.6, CI 1.5–39.3) with no difference in NRM or acute GVHD. Conclusions: OS and RFS were comparable to what has been observed in other large, single-center studies (OS 77%, RFS 71% at 2 years) and compared favorably to outcomes from the largest multi-center retrospective analyses. Full article
(This article belongs to the Special Issue Blood Stem Cell and Hematological Malignancies)
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27 pages, 6490 KB  
Article
Novel Tear Biomarkers in Ocular Graft Versus Host Disease Associated with Th1/Th2 Immune Responses: A Case Series and Literature Review
by Mihaela-Madalina Timofte-Zorila, Mariana Pavel-Tanasa, Daniela Constantinescu, Corina Cianga, Daniel Constantin Branisteanu, Giuseppe Giannaccare, Filippo Lixi, Angela Dascalescu, Nicoleta Vlas, Sabina Turcas and Cristina Preda
Int. J. Mol. Sci. 2025, 26(9), 4311; https://doi.org/10.3390/ijms26094311 - 1 May 2025
Cited by 1 | Viewed by 2237
Abstract
Ocular graft versus host disease (oGVHD) is a common complication of allogeneic hematopoietic stem cell transplantation and may be associated with dry eye disease and chronic inflammation and fibrosis. Immune dysregulation, particularly the Th1/Th2 imbalance, plays a key role in the progression of [...] Read more.
Ocular graft versus host disease (oGVHD) is a common complication of allogeneic hematopoietic stem cell transplantation and may be associated with dry eye disease and chronic inflammation and fibrosis. Immune dysregulation, particularly the Th1/Th2 imbalance, plays a key role in the progression of oGVHD. This case study presents two oGVHD patients (a 20-year-old with acute oGVHD and a 59-year-old with chronic oGVHD), analyzing clinical dry eye parameters (Schirmer test I, tear film break-up time, Ocular Surface Disease Index (OSDI), and kerato-conjunctival staining) alongside tear biomarkers. A 27-plex tear cytokine analysis was performed using the Luminex200 platform, assessing various biomarkers against a control group-defined normal range. Key biomarkers included beta2-microglobulin (β2-MG), complement components, chemokines, growth factors, and both pro-inflammatory and anti-inflammatory cytokines, as well a series of soluble ligand and receptors. The study identified distinct biomarker progression patterns during topical corticosteroid treatment in the acute oGHVD patient, suggesting potential shifts in Th1/Th2 responses as the disease progressed. Notably, the soluble CD27, TNF-related apoptosis-inducing ligand (TRAIL) receptor 2 (TRAIL-R2), chemokine ligand 2 (CCL2), and IL-1β, initially elevated, normalized during treatment, while tear-soluble Fas remained highly elevated (>400-fold). Conversely, soluble TRAIL, which was initially at very low levels (100-fold lower), increased during treatment and reached normal tear levels, coinciding with improvements in the clinical ocular inflammation symptoms and OSDI score. This case study also highlights potential differences between acute and chronic oGVHD, particularly in the distinct patterns of novel tear biomarkers such as CD27, TRAIL/TRAIL-R2, and CCL2. Enhancing our understanding of biomarker dynamics may improve disease monitoring and pave the way for personalized management strategies to improve patient outcomes. Full article
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